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Buso H, Discardi C, Bez P, Muscianisi F, Ceccato J, Milito C, Firinu D, Landini N, Jones MG, Felice C, Rattazzi M, Scarpa R, Cinetto F. Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review. Biomedicines 2024; 12:1503. [PMID: 39062076 PMCID: PMC11275071 DOI: 10.3390/biomedicines12071503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/24/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024] Open
Abstract
Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.
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Affiliation(s)
- Helena Buso
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Claudia Discardi
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Patrick Bez
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Francesco Muscianisi
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Jessica Ceccato
- Haematology and Clinical Immunology Unit, Department of Medicine (DIMED), University of Padova, 35124 Padova, Italy
- Veneto Institute of Molecular Medicine (VIMM), 35131 Padova, Italy
| | - Cinzia Milito
- Department of Molecular Medicine, “Sapienza” University of Rome, 00161 Rome, Italy
| | - Davide Firinu
- Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
| | - Nicholas Landini
- Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I Hospital, “Sapienza” University of Rome, 00161 Rome, Italy
| | - Mark G. Jones
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 YD, UK;
- Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
| | - Carla Felice
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Marcello Rattazzi
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Riccardo Scarpa
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
| | - Francesco Cinetto
- Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, University of Padova, 35124 Padova, Italy (C.F.); (M.R.); (R.S.); (F.C.)
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Smits BM, Boland SL, Hol ME, Dandis R, Leavis HL, de Jong PA, Prevaes SMPJ, Mohamed Hoesein FAA, van Montfrans JM, Ellerbroek PM. Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:1037-1048.e3. [PMID: 38182096 DOI: 10.1016/j.jaip.2023.12.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 12/21/2023] [Accepted: 12/26/2023] [Indexed: 01/07/2024]
Abstract
BACKGROUND Patients with primary antibody deficiency (PAD) frequently suffer from pulmonary complications, associated with severe morbidity and mortality. Hence, regular pulmonary screening by computed tomography (CT) scanning is advised. However, predictive risk factors for pulmonary morbidity are lacking. OBJECTIVE To identify patients with PAD at risk for pulmonary complications necessitating regular CT screening. METHODS A retrospective, longitudinal cohort study of patients with PAD (median follow-up 7.4 [2.3-14.8] years) was performed. CTs were scored using the modified Brody-II scoring system. Clinical and laboratory parameters were retrospectively collected. Potential risk factors were identified by univariate analysis when P < .2 and confirmed by multivariable logistic regression when P < .05. RESULTS The following independent risk factors for progression of airway disease (AD) were identified: (1) diagnosis of X-linked agammaglobulinemia (XLA), (2) recurrent airway infections (2.5/year), and (3) the presence of AD at baseline. Signs of AD progression were detected in 5 of 11 patients with XLA and in 17 of 80 of the other patients with PAD. Of the 22 patients who progressed, 17 had pre-existent AD scores ≥7.0%. Increased AD scores were related to poorer forced expiratory volume in 1 second values and chronic cough. Common variable immunodeficiency and increased CD4 effector/memory cells were risk factors for an interstitial lung disease (ILD) score ≥13.0%. ILD ≥13.0% occurred in 12 of 80 patients. Signs of ILD progression were detected in 8 of 80 patients, and 4 of 8 patients showing progression had pre-existent ILD scores ≥13.0%. CONCLUSION We identified risk factors that distinguished patients with PAD at risk for AD and ILD presence and progression, which could guide future screening frequency; however, independent and preferably prospective validation is needed.
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Affiliation(s)
- Bas M Smits
- Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Sharisa L Boland
- Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marjolein E Hol
- Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Rana Dandis
- Research Department, Trial and Datacenter, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Helen L Leavis
- Department of Rheumatology and Clinical Immunology, Utrecht University, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Pim A de Jong
- Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Sabine M P J Prevaes
- Department of Pediatric Pulmonology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | - Joris M van Montfrans
- Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Pauline M Ellerbroek
- Department of Internal Medicine, Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands.
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Correa-Jimenez O, Restrepo-Gualteros S, Nino G, Cunningham-Rundles C, Sullivan KE, Fuleihan RL, Gutierrez MJ. Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency in the USIDNET Registry. J Clin Immunol 2023; 43:2208-2220. [PMID: 37932514 PMCID: PMC11310578 DOI: 10.1007/s10875-023-01593-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 09/23/2023] [Indexed: 11/08/2023]
Abstract
BACKGROUND Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development. OBJECTIVE To identify respiratory comorbidities associated with bronchiectasis in patients with CVID. METHODS A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis. RESULTS One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05-2.75), sinusitis (OR = 2.06 95%CI 1.38-3.09), pneumonia (OR = 2.70 95%CI 1.88-3.88), COPD (OR = 2.66 95%CI 1.51-4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41-3.91) were independently associated with the development of bronchiectasis in this population. CONCLUSION These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.
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Affiliation(s)
- Oscar Correa-Jimenez
- Allergy and Immunology Unit, Fundación Neumológica Colombiana, Bogotá, D.C., Colombia
| | - Sonia Restrepo-Gualteros
- Department of Pediatrics, Universidad Nacional de Colombia School of Medicine, Bogotá, D.C., Colombia
| | - Gustavo Nino
- Division of Pediatric Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, George Washington University School of Medicine, Washington, DC, USA
| | - Charlotte Cunningham-Rundles
- Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kathleen E Sullivan
- Division of Pediatric Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Ramsay L Fuleihan
- Division of Allergy & Immunology, Columbia University Irving Medical Center, New York, NY, USA
| | - Maria J Gutierrez
- Division of Pediatric Allergy, Immunology and Rheumatology, Johns Hopkins University, 600 N. Wolfe St, CMSC 1102, Baltimore, MD, 21287, USA.
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Coimbra MT, Silvano J, Martins LS. Medical Challenges of a Common Variable Immunodeficiency With a TNFRSF13B Gene Mutation in a Simultaneous Kidney and Pancreas Transplant Recipient. Cureus 2023; 15:e44211. [PMID: 37767270 PMCID: PMC10521941 DOI: 10.7759/cureus.44211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2023] [Indexed: 09/29/2023] Open
Abstract
Common variable immune deficiency (CVID) is a primary immunodeficiency disorder, with hypogammaglobulinemia and increased susceptibility to recurrent infections, autoimmune disorders, granulomatous diseases and malignancy. Among the solid organ transplant (SOT) recipient population, those with primary immunodeficiency disorders under chronic immunosuppression therapy can theoretically be at higher risk of atypical infections, autoimmune complications and disease recurrence with suboptimal long term graft survival, but literature is scarce. Here, we report a 27-year-old female with type 1 diabetes mellitus, complicated with nephropathy that progressed to end-stage renal disease (ESRD), who had a history of a chronic inflammatory response dysregulation, with chronic monoarthritis, persistent elevation of inflammation markers, recurrent infections, low immunoglobulin G (IgG) and A (IgA) serum levels, a slightly decreased population of memory B cells at flow cytometric immunophenotyping, and a confirmed pathological heterozygous mutation in the tumor necrosis factor receptor superfamily 13B (TNFRSF13B), with a suspected diagnosis of CVID. Whilst on hemodialysis, she received a simultaneous kidney and pancreas transplant from a standard criteria donor (SCD), and our induction and maintenance immunosuppression protocol and prophylaxis regimen allowed for a successful transplant with immediate pancreatic function, with no evidence of renal graft rejection upon biopsy in the early post-transplant period, and no novel episodes of serious infectious complications were recorded during a follow-up period of six months.
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Affiliation(s)
| | - José Silvano
- Nephrology, Centro Hospitalar Universitário do Porto, Porto, PRT
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Bintalib HM, van de Ven A, Jacob J, Davidsen JR, Fevang B, Hanitsch LG, Malphettes M, van Montfrans J, Maglione PJ, Milito C, Routes J, Warnatz K, Hurst JR. Diagnostic testing for interstitial lung disease in common variable immunodeficiency: a systematic review. Front Immunol 2023; 14:1190235. [PMID: 37223103 PMCID: PMC10200864 DOI: 10.3389/fimmu.2023.1190235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 04/17/2023] [Indexed: 05/25/2023] Open
Abstract
Introduction Common variable immunodeficiency related interstitial lung disease (CVID-ILD, also referred to as GLILD) is generally considered a manifestation of systemic immune dysregulation occurring in up to 20% of people with CVID. There is a lack of evidence-based guidelines for the diagnosis and management of CVID-ILD. Aim To systematically review use of diagnostic tests for assessing patients with CVID for possible ILD, and to evaluate their utility and risks. Methods EMBASE, MEDLINE, PubMed and Cochrane databases were searched. Papers reporting information on the diagnosis of ILD in patients with CVID were included. Results 58 studies were included. Radiology was the investigation modality most commonly used. HRCT was the most reported test, as abnormal radiology often first raised suspicion of CVID-ILD. Lung biopsy was used in 42 (72%) of studies, and surgical lung biopsy had more conclusive results compared to trans-bronchial biopsy (TBB). Analysis of broncho-alveolar lavage was reported in 24 (41%) studies, primarily to exclude infection. Pulmonary function tests, most commonly gas transfer, were widely used. However, results varied from normal to severely impaired, typically with a restrictive pattern and reduced gas transfer. Conclusion Consensus diagnostic criteria are urgently required to support accurate assessment and monitoring in CVID-ILD. ESID and the ERS e-GLILDnet CRC have initiated a diagnostic and management guideline through international collaboration. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022276337.
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Affiliation(s)
- Heba M. Bintalib
- University College London (UCL) Respiratory, University College London, London, United Kingdom
- Department of Respiratory Care, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia
| | - Annick van de Ven
- Departments of Internal Medicine & Allergology, Rheumatology & Clinical Immunology, University Medical Center Groningen, Groningen, Netherlands
| | - Joseph Jacob
- University College London (UCL) Respiratory, University College London, London, United Kingdom
- Satsuma Lab, Centre for Medical Image Computing, University College London (UCL), London, United Kingdom
| | - Jesper Rømhild Davidsen
- South Danish Center for Interstitial Lung Diseases (SCILS), Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark
- Odense Respiratory Research Unit (ODIN), Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Børre Fevang
- Centre for Rare Disorders, Division of Paediatric and Adolescent Health, Oslo University Hospital, Oslo, Norway
- Section of Clinical Immunology and Infectious Diseases, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Leif G. Hanitsch
- Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1 and Berlin Institute of Health, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, Berlin, Germany
| | - Marion Malphettes
- Department of Clinic Immunopathology, Hôpital Saint-Louis, Paris, France
| | - Joris van Montfrans
- Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Childrens Hospital, University Medical Center Utrecht (UMC), Utrecht, Netherlands
| | - Paul J. Maglione
- Section of Pulmonary, Allergy, Sleep, and Critical Care Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
| | - Cinzia Milito
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - John Routes
- Division of Allergy, Asthma and Immunology, Department of Pediatrics, Medicine, Microbiology and Immunology, Medical College Wisconsin, Milwaukee, WI, United States
| | - Klaus Warnatz
- Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - John R. Hurst
- University College London (UCL) Respiratory, University College London, London, United Kingdom
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Syed MN, Kutac C, Miller JM, Marsh R, Sullivan KE, Cunningham-Rundles C, Fuleihan RL, Kheradmand F, Hajjar J. Risk Factors of Pneumonia in Primary Antibody Deficiency Patients Receiving Immunoglobulin Therapy: Data from the US Immunodeficiency Network (USIDNET). J Clin Immunol 2022; 42:1545-1552. [PMID: 35779201 DOI: 10.1007/s10875-022-01317-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/22/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Despite immunoglobulin replacement (IgRT) therapy, some patients with primary antibody deficiency (PAD) continue to develop respiratory infections. Recurrent and severe respiratory infections, particularly pneumonia, can lead to significant morbidity and mortality. Therefore, we sought to determine the risk factors of developing pneumonia in PAD patients, already receiving IgRT. METHODS We evaluated clinical and laboratory features of PAD patients enrolled in the US Immune Deficiency Network (USIDNET) registry by April 2017. Patients were included if they met the following criteria: (1) PAD diagnosis (common variable immunodeficiency (CVID), agammaglobulinemia, hypogammaglobinemia, and specific antibody deficiency (SAD) and (2) available data on infections before and after IgRT. Patients were excluded if they were not receiving IgRT, or if no pre/post infections data were available. Descriptive and multivariable logistic regression analyses were used to identify factors associated with pneumonia post-IgRT. RESULTS A total of 1232 patients met the inclusion criteria. Following IgRT, 218 patients (17.7%) were reported to have at least one pneumonia episode. Using multivariate logistic regression analysis, we found a statistically significant increased risk of pneumonia in patients with asthma (OR: 2.55, 95% CI (1.69-3.85), p < 0.001) bronchiectasis (OR: 3.94, 95% CI (2.29-6.80), p < 0.001), interstitial lung disease (ILD) (OR: 3.28, 95%CI (1.43-7.56), p < 0.005), splenomegaly (OR: 2.02, 95%CI (1.08-3.76), p < 0.027), allergies (OR: 2.44, 95% CI [1.44-4.13], p = 0.001), and patients who were not on immunosuppressives (OR: 1.61; 95%CI [1.06-2.46]; p = 0.027). For every 50 unit increase in IgA, the odds of reporting pneumonia post IgRT decreased (OR: 0.86, 95% CI [0.73-1.02], p = 0.062). Infectious organisms were reported in 35 of 218 patients who reported pneumonia after IgRT. Haemophilus influenzae was the most frequently reported (n = 11, 31.43%), followed by Streptococcus pneumoniae (n = 7, 20.00%). CONCLUSION Our findings suggest PAD patients with chronic and structural lung disease, splenomegaly, and allergies were associated with persistent pneumonia. However, our study is limited by the cross-sectional nature of the USIDNET database and limited longitudinal data. Further studies are warranted to identify susceptible causes and explore targeted solutions for prevention and associated morbidity and mortality. CLINICAL IMPLICATIONS Patients with primary antibody deficiency with structural lung disease, allergies, and splenomegaly are associated with persistent pneumonia post-IgRT.
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Affiliation(s)
- Maha N Syed
- The William T Shearer Center for Human Immunobiology at Texas Children's Hospital, Houston, TX, USA
- Department of Pediatrics, Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine, Houston, TX, USA
| | - Carleigh Kutac
- Department of Pediatrics, Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine, Houston, TX, USA
| | - Jennifer M Miller
- Department of Pediatrics, Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine, Houston, TX, USA
| | - Rebecca Marsh
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital, and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
| | - Kathleen E Sullivan
- Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Charlotte Cunningham-Rundles
- Departments of Medicine and Pediatrics, Division of Allergy and Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ramsay L Fuleihan
- Division of Pediatric Allergy, Immunology and Rheumatology, Columbia University Medical Center, New York, NY, USA
| | - Farrah Kheradmand
- Biology of Inflammation Center, Baylor College of Medicine, TX, Houston, USA
- Center for Translational Research On Inflammatory Diseases (CTRID), Michael E. DeBakey Department of Veterans Affairs, TX, Houston, USA
| | - Joud Hajjar
- The William T Shearer Center for Human Immunobiology at Texas Children's Hospital, Houston, TX, USA.
- Department of Pediatrics, Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine, Houston, TX, USA.
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Zissler UM, Thron A, Eckrich J, Bakhtiar S, Schubert R, Zielen S. Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis-related small airway dysfunction. Clin Exp Allergy 2022; 52:760-773. [PMID: 35353925 DOI: 10.1111/cea.14140] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/09/2022] [Accepted: 03/27/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND The progression of chronic destructive lung disease in patients with humoral immunodeficiency (ID) and concomitant development of bronchiectasis is difficult to prevent. Lung function tests in these patients typically show bronchial obstruction of the small airways in combination with increased air trapping in the distal airways, which is consistent with small airway dysfunction. OBJECTIVE The objective was to assess the grade of chronic lower airway inflammation and small airway dysfunction from induced sputum and the corresponding local pro-inflammatory mediator pattern to discriminate patients affected by bronchiectasis-related Small Airway Dysfunction (SAD). METHODS In a prospective design, 22 patients with ID (14 CVID, 3 XLA, 3 hyper-IgM syndrome, 1 hyper-IgE syndrome and low IgG levels due to treatment with rituximab and 1 SCID after BMT and persistent humoral defect) and 21 healthy controls were examined. Lung function, Fraction Expiratory Nitric Oxide (FeNO) and pro-inflammatory cytokine levels were compared in subsets of patients with (ID + BE) and without bronchiectasis (ID) pre-stratified using high-resolution computed tomography (HRCT) scans and control subjects. RESULTS Analysis of induced sputum showed significantly increased total cell counts and severe neutrophilic inflammation in ID. The concomitant SAD revealed higher total cell numbers compared to ID. Bronchial inflammation in ID is clearly mirrored by pro-inflammatory mediators IL-1β, IL-6 and CXCL-8, whilst TNF-α revealed a correlation with lung function parameters altered in the context of bronchiectasis-related Small Airway Dysfunction. CONCLUSIONS In spite of immunoglobulin substitution, bronchial inflammation was dominated by neutrophils and was highly increased in patients with ID + BE. Notably, the pro-inflammatory cytokines in patients with ID were significantly increased in induced sputum. The context-dependent cytokine pattern in relation to the presence of concomitant bronchiectasis associated with SAD in ID patients could be helpful in delimiting ID patient subgroups and individualizing therapeutic approaches.
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Affiliation(s)
- Ulrich M Zissler
- Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Germany, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Aljoscha Thron
- Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany
| | - Jonas Eckrich
- Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany
| | - Shahrzad Bakhtiar
- Division for Stem Cell Transplantation, Immunology and Intensive Care Unit, Department for Children and Adolescents, Goethe University, Frankfurt, Germany
| | - Ralf Schubert
- Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany
| | - Stefan Zielen
- Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany
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Yazdani R, Aghamohammadi A, Rezaei N. Application of Flow Cytometry in Predominantly Antibody Deficiencies. Endocr Metab Immune Disord Drug Targets 2020; 21:647-663. [PMID: 32693771 DOI: 10.2174/1871530320666200721013312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 05/12/2020] [Accepted: 05/21/2020] [Indexed: 11/30/2022]
Abstract
Predominantly antibody deficiencies (PADs) are a heterogeneous group of primary immunodeficiency disorders (PIDs), consisting of recurrent infections, autoimmunity, inflammation, and other immune complications. In the recent years, several immunological and genetic defects have been recognized in PADs. Currently, 45 distinct PAD disorders with 40 different genetic defects have been identified based on the 2019 IUIS classification. Genetic analysis is helpful for diagnosing PIDs; however, genetic studies are expensive, time-consuming, and unavailable everywhere. Flow cytometry is a highly sensitive tool for evaluating the immune system and diagnosing PADs. In addition to cell populations and subpopulations assay, flow cytometry can measure cell surface, intracellular and intranuclear proteins, biological changes associated with specific immune defects, and certain functional immune abnormalities. These capabilities help in rapid diagnostic and prognostic assessment as well as in evaluating the pathogenesis of PADs. For the first time, this review particularly provides an overview of the application of flow cytometry for diagnosis, immunophenotyping, and determining the pathogenesis of PADs.
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Affiliation(s)
- Reza Yazdani
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Asghar Aghamohammadi
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
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Evaluation of pulmonary findings in patients with humoral immunodeficiency. Turk Arch Pediatr 2020; 55:174-183. [PMID: 32684763 PMCID: PMC7344133 DOI: 10.14744/turkpediatriars.2020.46656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 01/07/2020] [Indexed: 11/20/2022]
Abstract
Aim: To determine the frequency of sinopulmonary infections, detect changes in the respiratory system, and measure functional capacity of the lungs in our patients with humoral immunodeficiency. Material and Methods: Fifty-six patients with humoral immunodeficiency were enrolled in this study. The clinical, laboratory, and radiologic data, and pulmonary function tests of the subjects were evaluated from their file records, retrospectively. Results: The distribution of our patients was as follows: 25 patients had common variable immune deficiency, three patients had X-linked agammaglobulinemia, five patients had hyper immunoglobulin M syndrome, 19 patients had deficiency of immunoglobulin G subset, and four patients had selective immunoglobulin A deficiency. The most common symptom of the patients was chronic cough (n=47, 83.9%). The most common pathologies on high-resolution computed tomography of the chest were atelectasis and bronchiectasis (27.7%). The most common pathology in pulmonary function tests was the presence of moderate obstructive patterns along with restrictive patterns (n=6,12.5%). The FEV 1, FVC, and FEF 25–75 values were significantly lower in patients with common variable immunodeficiency compared with the patients who had IgG subset deficiencies (p=0.001, p=0.01, p=0.01). Among the patients who were treated with intravenous immunoglobulin, the age at the diagnosis of immunodeficiency was higher in patients with bronchiectasis (14.2±8.4 years) compared with those without bronchiectasis (10.1±11.4 years) (p=0.04). Conclusion: Clinical findings are not sufficient to monitor the structural and functional changes in the respiratory system, and patients should be evaluated using high-resolution computed tomography of the chest and pulmonary function tests.
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10
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Maglione PJ. Chronic Lung Disease in Primary Antibody Deficiency: Diagnosis and Management. Immunol Allergy Clin North Am 2020; 40:437-459. [PMID: 32654691 DOI: 10.1016/j.iac.2020.03.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Chronic lung disease is a complication of primary antibody deficiency (PAD) associated with significant morbidity and mortality. Manifestations of lung disease in PAD are numerous. Thoughtful application of diagnostic approaches is imperative to accurately identify the form of disease. Much of the treatment used is adapted from immunocompetent populations. Recent genomic and translational medicine advances have led to specific treatments. As chronic lung disease has continued to affect patients with PAD, we hope that continued advancements in our understanding of pulmonary pathology will ultimately lead to effective methods that alleviate impact on quality of life and survival.
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Affiliation(s)
- Paul J Maglione
- Pulmonary Center, Boston University School of Medicine, 72 East Concord Street, R304, Boston, MA 02118, USA.
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11
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Fekrvand S, Yazdani R, Olbrich P, Azizi G, Shirzadi R, Modaresi M, Sohani M, Delavari S, Kalantari A, Shariat M, Shafiei A, Lu N, Hassanpour G, Rahimi Hajiabadi M, Ashournia P, Razaghian A, Asgharyan M, Shahraki-Ghadimi Z, Rouhani R, Hoda Fallah F, Rezaei N, Abolhassani H, Aghamohammadi A. Evaluation of respiratory complications in patients with X-linked and autosomal recessive agammaglobulinemia. Pediatr Allergy Immunol 2020; 31:405-417. [PMID: 32058651 DOI: 10.1111/pai.13228] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 01/23/2020] [Accepted: 01/24/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Congenital agammaglobulinemia is the first primary immunodeficiency disorder characterized by a defect in B lymphocyte development and subsequently decreased immunoglobulin levels. These patients are prone to suffer from recurrent infections mostly involving the respiratory tract. In this study, we aimed to describe in detail respiratory tract complications as the most prominent clinical feature among agammaglobulinemic patients. METHODS A total number of 115 patients were included. Demographic, clinical, and genetic data were collected from the patients' medical records. Among the available patients, pulmonary function tests (PFTs) and/or high-resolution computed tomography (HRCT) were performed. RESULTS Respiratory tract complications (85.2%) especially pneumonia (62.6%) were the most prominent clinical features in our cohort. Among patients with abnormal PFT results (N = 19), a mixed respiratory pattern was observed in 36.8%. HRCT was carried out in 29 patients; Bhalla scoring-based evaluation of these patients indicated excellent (44.8%), followed by good (34.5%) and mild (20.7%) results. Bronchiectasis was found in 13 patients undergoing HRCT (44.8%). We found significant inverse correlations between the Bhalla score and incidence rate of pneumonia, as well as the presence of bronchiectasis. Patients with abnormal PFT results had statistically significant higher bronchiectasis frequency and lower Bhalla scores compared to those with normal results. Forty-one patients were deceased, and here, respiratory failure was the most common cause of death (45.5%). CONCLUSION High prevalence of respiratory tract infections among agammaglobulinemic patients and subsequent progression to permanent lung damage highlights the importance of implementing respiratory evaluation as part of routine follow-up program of agammaglobulinemic patients. Physicians should be aware of this and regularly monitor the respiratory function of these patients to allow for timely diagnosis and treatment initiation aiming to improve patients' prognosis and quality of life.
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Affiliation(s)
- Saba Fekrvand
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Reza Yazdani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Peter Olbrich
- Sección de Infectología e Inmunopatología, Unidad de Pediatría, Hospital Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | - Gholamreza Azizi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Rohola Shirzadi
- Department of Pediatric Pulmonary and Sleep Medicine, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Modaresi
- Department of Pediatric Pulmonary and Sleep Medicine, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Sohani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Samaneh Delavari
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Arash Kalantari
- Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansoureh Shariat
- Department of Allergy and Clinical Immunology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Shafiei
- The Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Na Lu
- State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Gholamreza Hassanpour
- Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Maziar Rahimi Hajiabadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Parisa Ashournia
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Anahita Razaghian
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Marzieh Asgharyan
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Zahra Shahraki-Ghadimi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Roja Rouhani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Hoda Fallah
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.,Network for Immunology in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hassan Abolhassani
- Research Center for Primary Immunodeficiencies, Iran University of Medical Sciences, Tehran, Iran.,Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at the Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Asghar Aghamohammadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
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12
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Patrawala M, Cui Y, Peng L, Fuleihan RL, Garabedian EK, Patel K, Guglani L. Pulmonary Disease Burden in Primary Immune Deficiency Disorders: Data from USIDNET Registry. J Clin Immunol 2020; 40:340-349. [PMID: 31919711 DOI: 10.1007/s10875-019-00738-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Accepted: 12/18/2019] [Indexed: 12/23/2022]
Abstract
PURPOSE Pulmonary manifestations are common in patients with primary immunodeficiency disorders (PIDs) but the prevalence, specific diseases, and their patterns are not well characterized. METHODS We conducted a retrospective analysis of pulmonary diseases reported in the database of the United States Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation. PIDs were categorized into 10 groups and their demographics, pulmonary diagnoses and procedures, infections, prophylaxis regimens, and laboratory findings were analyzed. RESULTS A total of 1937 patients with various PIDs (39.3% of total patients, 49.6% male, average age 37.9 years (SD = 22.4 years)) were noted to have a pulmonary disease comorbidity. Pulmonary diseases were categorized into broad categories: airway (86.8%), parenchymal (18.5%), pleural (4.6%), vascular (4.3%), and other (13.9%) disorders. Common variable immune deficiency (CVID) accounted for almost half of PIDs associated with airway, parenchymal, and other pulmonary disorders. Pulmonary procedures performed in 392 patients were mostly diagnostic (77.3%) or therapeutic (16.3%). These patients were receiving a wide variety of treatments, which included immunoglobulin replacement (82.1%), immunosuppressive (32.2%), anti-inflammatory (12.7%), biologic (9.3%), and cytokine (7.6%)-based therapies. Prophylactic therapy was being given with antibiotics (18.1%), antifungal (3.3%), and antiviral (2.2%) medications, and 7.1% of patients were on long-term oxygen therapy due to advanced lung disease. CONCLUSIONS Pulmonary manifestations are common in individuals with PID, but long-term pulmonary outcomes are not well known in this group of patients. Further longitudinal follow-up will help to define long-term prognosis of respiratory comorbidities and optimal treatment modalities.
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Affiliation(s)
- Meera Patrawala
- Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory University, 2015 Uppergate Drive, Atlanta, GA, 30322, USA
| | - Ying Cui
- Department of Biostatistics, Emory University, Atlanta, GA, USA
| | - Limin Peng
- Department of Biostatistics, Emory University, Atlanta, GA, USA
| | - Ramsay L Fuleihan
- Division of Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Elizabeth K Garabedian
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Kiran Patel
- Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory University, 2015 Uppergate Drive, Atlanta, GA, 30322, USA
| | - Lokesh Guglani
- Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Emory University, 2015 Uppergate Drive, Atlanta, GA, 30322, USA.
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13
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Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients. Immunol Lett 2019; 210:55-62. [DOI: 10.1016/j.imlet.2019.05.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 04/14/2019] [Accepted: 05/02/2019] [Indexed: 12/31/2022]
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14
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Weinberger T, Fuleihan R, Cunningham-Rundles C, Maglione PJ. Factors Beyond Lack of Antibody Govern Pulmonary Complications in Primary Antibody Deficiency. J Clin Immunol 2019; 39:440-447. [PMID: 31089938 DOI: 10.1007/s10875-019-00640-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 05/01/2019] [Indexed: 01/12/2023]
Abstract
PURPOSE Pulmonary complications occur frequently in primary antibody deficiency (PAD). While the impact of antibody deficiency may appear implicit for certain respiratory infections, immunoglobulin replacement therapy does not completely ameliorate pulmonary complications in PAD. Thus, there may be antibody-independent factors influencing susceptibility to respiratory disease in PAD, but these remain incompletely defined. METHODS We harnessed the multicenter US Immunodeficiency Network primary immunodeficiency registry to compare prevalence of asthma, bronchiectasis, interstitial lung disease (ILD), and respiratory infections between two forms of PAD: common variable immunodeficiency (CVID) and x-linked agammaglobulinemia (XLA). We also defined the clinical and immunological characteristics associated with ILD and asthma in CVID. RESULTS Asthma, bronchiectasis, ILD, pneumonia, and upper respiratory infections were more prevalent in CVID than XLA. ILD was associated with autoimmunity, bronchiectasis, and pneumonia as well as fewer B and T cells in CVID. Asthma was the most common chronic pulmonary complication and associated with lower IgA and IgM in CVID. Age of symptom onset or CVID diagnosis was unrelated with ILD or asthma. CONCLUSION Despite having less severe immunoglobulin deficiency than XLA, respiratory infections, ILD, and asthma were more common in CVID. Among CVID patients, ILD was associated with autoimmunity and reduced lymphocytes and asthma with lower immunoglobulins. Though our results are tempered by registry limitations, they provide evidence that factors beyond lack of antibody promote pulmonary complications in PAD. Efforts to understand how genetic etiology, nature of concurrent T cell deficiency, and propensity for autoimmunity shape pulmonary disease may improve treatment of PAD.
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Affiliation(s)
- Tamar Weinberger
- Department of Medicine, Center for Allergy, Asthma, and Immune Disorders, Hackensack University Medical Center, Hackensack, NJ, USA
| | - Ramsay Fuleihan
- Department of Pediatrics, Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | - Charlotte Cunningham-Rundles
- Department of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Paul J Maglione
- Department of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Medicine, Section of Pulmonary, Allergy, Sleep & Critical Care Medicine, School of Medicine, Boston University, Boston, MA, USA. .,Pulmonary Center, School of Medicine, Boston University, 72 East Concord Street, R304, Boston, MA, 02118, USA.
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15
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Maglione PJ, Gyimesi G, Cols M, Radigan L, Ko HM, Weinberger T, Lee BH, Grasset EK, Rahman AH, Cerutti A, Cunningham-Rundles C. BAFF-driven B cell hyperplasia underlies lung disease in common variable immunodeficiency. JCI Insight 2019; 4:122728. [PMID: 30843876 DOI: 10.1172/jci.insight.122728] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 01/25/2019] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and is frequently complicated by interstitial lung disease (ILD) for which etiology is unknown and therapy inadequate. METHODS Medical record review implicated B cell dysregulation in CVID ILD progression. This was further studied in blood and lung samples using culture, cytometry, ELISA, and histology. Eleven CVID ILD patients were treated with rituximab and followed for 18 months. RESULTS Serum IgM increased in conjunction with ILD progression, a finding that reflected the extent of IgM production within B cell follicles in lung parenchyma. Targeting these pulmonary B cell follicles with rituximab ameliorated CVID ILD, but disease recurred in association with IgM elevation. Searching for a stimulus of this pulmonary B cell hyperplasia, we found B cell-activating factor (BAFF) increased in blood and lungs of progressive and post-rituximab CVID ILD patients and detected elevation of BAFF-producing monocytes in progressive ILD. This elevated BAFF interacts with naive B cells, as they are the predominant subset in progressive CVID ILD, expressing BAFF receptor (BAFF-R) within pulmonary B cell follicles and blood to promote Bcl-2 expression. Antiapoptotic Bcl-2 was linked with exclusion of apoptosis from B cell follicles in CVID ILD and increased survival of naive CVID B cells cultured with BAFF. CONCLUSION CVID ILD is driven by pulmonary B cell hyperplasia that is reflected by serum IgM elevation, ameliorated by rituximab, and bolstered by elevated BAFF-mediated apoptosis resistance via BAFF-R. FUNDING NIH, Primary Immune Deficiency Treatment Consortium, and Rare Disease Foundation.
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Affiliation(s)
| | - Gavin Gyimesi
- Division of Clinical Immunology, Department of Medicine
| | | | - Lin Radigan
- Division of Clinical Immunology, Department of Medicine
| | | | | | - Brian H Lee
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Emilie K Grasset
- Division of Clinical Immunology, Department of Medicine.,Experimental Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Adeeb H Rahman
- Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Andrea Cerutti
- Division of Clinical Immunology, Department of Medicine.,Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.,Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain
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16
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Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, Gharagozlou M, Movahedi M, Hamidieh AA, Behniafard N, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Shirkani A, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari A, Mansouri M, Mesdaghi M, Babaie D, Ahanchian H, Khoshkhui M, Soheili H, Eslamian MH, Cheraghi T, Dabbaghzadeh A, Tavassoli M, Kalmarzi RN, Mortazavi SH, Kashef S, Esmaeilzadeh H, Tafaroji J, Khalili A, Zandieh F, Sadeghi-Shabestari M, Darougar S, Behmanesh F, Akbari H, Zandkarimi M, Abolnezhadian F, Fayezi A, Moghtaderi M, Ahmadiafshar A, Shakerian B, Sajedi V, Taghvaei B, Safari M, Heidarzadeh M, Ghalebaghi B, Fathi SM, Darabi B, Bazregari S, Bazargan N, Fallahpour M, Khayatzadeh A, Javahertrash N, Bashardoust B, Zamani M, Mohsenzadeh A, Ebrahimi S, Sharafian S, Vosughimotlagh A, Tafakoridelbari M, Rahim M, Ashournia P, Razaghian A, Rezaei A, Samavat A, Mamishi S, Khazaei HA, Mohammadi J, Negahdari B, Parvaneh N, Rezaei N, Lougaris V, Giliani S, Plebani A, Ochs HD, Hammarström L, Aghamohammadi A. Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 7:864-878.e9. [DOI: 10.1016/j.jaip.2018.09.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 12/15/2022]
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17
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Mahdaviani SA, Darougar S, Mansouri D, Tashayoie-Nejad S, Movahedi M, Aghdam KR, Ghaffaripour H, Baghaie N, Hassanzad M, Eslaminejad A, Fakharian A, Pourdowlat G, Heshmatnia J, Bakhshayeshkaram M, Boloursaz M, Tabarsi P, Hashemitari SK, Velayati AA. Pulmonary complications of predominantly antibody immunodeficiencies in a tertiary lung center. Interv Med Appl Sci 2018; 11:1-7. [PMID: 32148897 PMCID: PMC7044568 DOI: 10.1556/1646.10.2018.49] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Background and aims Respiratory infections are expressed very soon in the life in humoral immunodeficiencies and often lead to chronic irreversible complications such as bronchiectasis and chronic airflow limitation. This study was conducted to evaluate the pulmonary complications of predominantly antibody immunodeficiencies to show the benefits of timely diagnosis and appropriate therapy. Patients and methods The information of 48 patients involved with a type of predominantly antibody immunodeficiencies, including sex, type of primary immunodeficiency, age at the onset of symptoms, age at diagnosis, recurrent infections, respiratory symptoms, and pulmonary radiological and functional abnormalities were recorded and analyzed. Results In 48 patients evaluated, the mean age at diagnosis was 25.63 years. The mean diagnostic delay was estimated to be 13.62 years. The most recurring clinical manifestations, sinusitis (69.6%), otitis (43.5%), and recurrent pneumonia were the cause of frequent admissions in 68.8% of these patients. Bronchiectasis was frequently found (58.3%) in these patients mostly involving the middle and lower lobes (48.8% and 41.5%, respectively). Conclusions Respiratory complications, infectious or non-infectious, determine the prognosis of the disease in patients with predominantly antibody immunodeficiencies. Timely diagnosis and appropriate management may improve life expectancy and the quality of life in these patients.
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Affiliation(s)
- Seyed Alireza Mahdaviani
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Darougar
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Mansouri
- Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sabereh Tashayoie-Nejad
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahshid Movahedi
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Karim Rahimi Aghdam
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hosseinali Ghaffaripour
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nooshin Baghaie
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Hassanzad
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Eslaminejad
- Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Fakharian
- Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Guitti Pourdowlat
- Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jalal Heshmatnia
- Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehrdad Bakhshayeshkaram
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Boloursaz
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Karen Hashemitari
- Pediatric Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Velayati
- Mycobacteriology Research Centre (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Schütz K, Alecsandru D, Grimbacher B, Haddock J, Bruining A, Driessen G, de Vries E, van Hagen PM, Hartmann I, Fraioli F, Milito C, Mitrevski M, Quinti I, Serra G, Kelleher P, Loebinger M, Litzman J, Postranecka V, Thon V, Babar J, Condliffe AM, Exley A, Kumararatne D, Screaton N, Jones A, Bondioni MP, Lougaris V, Plebani A, Soresina A, Sirignano C, Spadaro G, Galal N, Gonzalez-Granado LI, Dettmer S, Stirling R, Chapel H, Lucas M, Patel S, Farber CM, Meyts I, Banerjee AK, Hackett S, Hurst JR, Warnatz K, Gathmann B, Baumann U. Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group. J Clin Immunol 2018; 39:45-54. [PMID: 30547383 DOI: 10.1007/s10875-018-0577-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Accepted: 11/26/2018] [Indexed: 01/31/2023]
Abstract
Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.
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Affiliation(s)
- Katharina Schütz
- Paediatric Immunology Unit, Department of Paediatric Pulmonology, Allergology and Neonatology, Hanover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany
| | - Diana Alecsandru
- Primary Immunodeficiencies Unit, Pediatrics, Hospital 12 Octubre, Madrid, Spain
- Clinical Immunology, Royal Free Hospital, London, UK
| | - Bodo Grimbacher
- Clinical Immunology, Royal Free Hospital, London, UK
- Centre for Chronic Immunodeficiency, University Medical Center of Freiburg, Freiburg, Germany
| | | | - Annemarie Bruining
- Dutch Cancer Institute, Antoni van Leeuwenhoek Hospital, The Hague, The Netherlands
| | - Gertjan Driessen
- Paediatric Immunology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
- Paediatrics, Juliana Children's Hospital/Haga Teaching Hospital, The Hague, The Netherlands
| | - Esther de Vries
- Jeroen Bosch Academy, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
- Tranzo, Tilburg University, Tilburg, The Netherlands
| | - Peter M van Hagen
- Immunology and Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Ieneke Hartmann
- Department of Radiology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Francesco Fraioli
- Radiology, Università degli Studi di Roma La Sapienza, Rome, Italy
- Institute of Nuclear Medicine, University College London, London, UK
| | - Cinzia Milito
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Milica Mitrevski
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Isabella Quinti
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Goffredo Serra
- Radiology, Università degli Studi di Roma La Sapienza, Rome, Italy
| | - Peter Kelleher
- Immunology Section Department of Medicine, Imperial College London, London, UK
| | - Michael Loebinger
- Department of Respiratory Medicine, Royal Brompton Hospital, London, UK
| | - Jiri Litzman
- Department of Clinical Immunology and Allergy, Faculty of Medicine, Masaryk University, St Anne's University Hospital, Brno, Czech Republic
| | - Vera Postranecka
- Department of Radiology, Faculty of Medicine, Masaryk University, St Anne's University Hospital, Brno, Czech Republic
| | - Vojtech Thon
- Department of Clinical Immunology and Allergy, Faculty of Medicine, Masaryk University, St Anne's University Hospital, Brno, Czech Republic
- RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Judith Babar
- Radiology, Addenbrooke's Hospital, Cambridge, UK
| | | | | | | | | | - Alison Jones
- Paediatric Immunology, Great Ormond Street Hospital, London, UK
| | | | - Vassilios Lougaris
- Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy
| | - Alessandro Plebani
- Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy
| | | | - Cesare Sirignano
- Radiology, IBB-CNR University of Naples Federico II, Naples, Italy
| | | | | | | | - Sabine Dettmer
- Diagnostic Radiology, Hanover Medical School, Hanover, Germany
| | - Robert Stirling
- Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Australia
| | - Helen Chapel
- Primary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Mary Lucas
- Primary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Smita Patel
- Primary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | | | - Isabelle Meyts
- Paediatric Immunology and Pulmonology, University Hospitals, Leuven, Belgium
| | | | - Scott Hackett
- Paediatric Immunology Department, Heartlands Hospital Birmingham, Birmingham, UK
| | - John R Hurst
- UCL Respiratory Medicine, University College London, London, UK
| | - Klaus Warnatz
- Centre for Chronic Immunodeficiency, University Medical Center of Freiburg, Freiburg, Germany
| | - Benjamin Gathmann
- ESID Registry Working Party, University Hospital Freiburg, Freiburg, Germany
| | - Ulrich Baumann
- Paediatric Immunology Unit, Department of Paediatric Pulmonology, Allergology and Neonatology, Hanover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.
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Cereser L, De Carli M, d’Angelo P, Zanelli E, Zuiani C, Girometti R. High-resolution computed tomography findings in humoral primary immunodeficiencies and correlation with pulmonary function tests. World J Radiol 2018; 10:172-183. [PMID: 30568751 PMCID: PMC6288673 DOI: 10.4329/wjr.v10.i11.172] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 09/22/2018] [Accepted: 10/07/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To compare high-resolution computed tomography (HRCT) findings between humoral primary immunodeficiencies (hPIDs) subtypes; to correlate these findings to pulmonary function tests (PFTs).
METHODS We retrospectively identified 52 consecutive adult patients with hPIDs who underwent 64-row HRCT and PFTs at the time of diagnosis. On a per-patient basis, an experienced radiologist recorded airway abnormalities (bronchiectasis, airway wall thickening, mucus plugging, tree-in-bud, and air-trapping) and parenchymal-interstitial abnormalities (consolidations, ground-glass opacities, linear and/or irregular opacities, nodules, and bullae/cysts) found on HRCT. The chi-square test was performed to compare the prevalence of each abnormality among patients with different subtypes of hPIDs. Overall logistic regression analysis was performed to assess whether HRCT findings predicted obstructive and/or restrictive PFTs results (absent-to-mild vs moderate-to-severe).
RESULTS Thirty-eight of the 52 patients with hPIDs showed common variable immunodeficiency disorders (CVID), while the remaining 14 had CVID-like conditions (i.e., 11 had isolated IgG subclass deficiencies and 3 had selective IgA deficiencies). The prevalence of most HRCT abnormalities was not significantly different between CVID and CVID-like patients (P > 0.05), except for linear and/or irregular opacities (prevalence of 31.6% in the CVID group and 0 in the CVID-like group; P = 0.0427). Airway wall thickening was the most frequent HRCT abnormality found in both CVID and CVID-like patients (71% of cases in both groups). The presence of tree-in-bud abnormalities was an independent predictor of moderate-to-severe obstructive defects at PFTs (Odds Ratio, OR, of 18.75, P < 0.05), while the presence of linear and/or irregular opacities was an independent predictor of restrictive defects at PFTs (OR = 13.00; P < 0.05).
CONCLUSION CVID and CVID-like patients showed similar HRCT findings. Tree-in-bud and linear and/or irregular opacities predicted higher risks of, respectively, obstructive and restrictive defects at PFTs.
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Affiliation(s)
- Lorenzo Cereser
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Marco De Carli
- Second Unit of Internal Medicine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Paola d’Angelo
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
- Department of Imaging, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy
| | - Elisa Zanelli
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Chiara Zuiani
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
| | - Rossano Girometti
- Institute of Radiology, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria Integrata di Udine, Udine 33100, Italy
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20
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Evaluation of Clinical and Immunological Characteristics of Children with Common Variable Immunodeficiency. Int J Pediatr 2018; 2018:3527480. [PMID: 29849668 PMCID: PMC5937368 DOI: 10.1155/2018/3527480] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 02/17/2018] [Accepted: 03/15/2018] [Indexed: 12/04/2022] Open
Abstract
Background Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder (PID) that typically presents with hypogammaglobulinemia and impaired antibody production. Objectives This study aimed to promote the awareness of CVID, whose clinical spectrum is quite broad. Methods The demographic, clinical, and laboratory characteristics of 12 children (seven males and five females) with CVID were analyzed retrospectively. The patients were diagnosed using the diagnostic criteria of the European Society for Primary Immunodeficiencies. Results The median disease onset age was 7.2 ± 4.1 years, and the mean diagnosis age was 11.6 ± 3.7 years. The diagnosis delay was 4.3 ± 2.6 years, and the parental consanguinity rate was 75%. Most patients presented with recurrent infections, including upper respiratory tract infections (n = 8), lower respiratory tract infections (n = 9), and gastroenteritis (n = 5). In addition, growth retardation (n = 9) and bronchiectasis (n = 5) were common comorbidities. Two patients presented with autoimmune thrombocytopenia and anemia, and one patient exhibited lung empyema. All the patients had immunoglobulin G deficiencies. Conclusion CVID is a heterogeneous disease, so the diagnosis is frequently delayed. In the CVID patients with pulmonary complications, relationships were seen with the diagnosis delay, symptom onset age, and lung infection prevalence. Overall, the early diagnosis and treatment of PIDs can preclude life-threatening complications.
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21
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Stubbs A, Bangs C, Shillitoe B, Edgar JD, Burns SO, Thomas M, Alachkar H, Buckland M, McDermott E, Arumugakani G, Jolles MS, Herriot R, Arkwright PD. Bronchiectasis and deteriorating lung function in agammaglobulinaemia despite immunoglobulin replacement therapy. Clin Exp Immunol 2018; 191:212-219. [PMID: 28990652 PMCID: PMC5758375 DOI: 10.1111/cei.13068] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2017] [Indexed: 12/21/2022] Open
Abstract
Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinaemia. We hypothesized that despite regular immunoglobulin therapy, some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. One hundred and thirty-nine (70%) of 199 patients aged 1-80 years from nine cities in the United Kingdom with agammaglobulinaemia currently listed on the UK Primary Immune Deficiency (UKPID) registry were recruited into this retrospective case study and their clinical and laboratory features analysed; 94% were male, 78% of whom had Bruton tyrosine kinase (BTK) gene mutations. All patients were on immunoglobulin replacement therapy and 52% had commenced therapy by the time they were 2 years old. Sixty per cent were also taking prophylactic oral antibiotics; 56% of patients had radiological evidence of bronchiectasis, which developed between the ages of 7 and 45 years. Multivariate analysis showed that three factors were associated significantly with bronchiectasis: reaching 18 years old [relative risk (RR) = 14·2, 95% confidence interval (CI) = 2·7-74·6], history of pneumonia (RR = 3·9, 95% CI = 1·1-13·8) and intravenous immunoglobulin (IVIG) rather than subcutaneous immunoglobulin (SCIG) = (RR = 3·5, 95% CI = 1·2-10·1), while starting immunoglobulin replacement after reaching 2 years of age, gender and recent serum IgG concentration were not associated significantly. Independent of age, patients with bronchiectasis had significantly poorer lung function [predicted forced expiratory volume in 1 s 74% (50-91)] than those without this complication [92% (84-101)] (P < 0·001). We conclude that despite immunoglobulin replacement therapy, many patients with agammaglobulinaemia can develop chronic lung disease and progressive impairment of lung function.
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Affiliation(s)
- A. Stubbs
- Paediatric Allergy and ImmunologyUniversity of ManchesterManchesterManchesterUK
| | - C. Bangs
- Paediatric Allergy and ImmunologyUniversity of ManchesterManchesterManchesterUK
- UKPIN UKPID Registry TeamUKPINLondonUK
| | - B. Shillitoe
- Department of ImmunologyGreat Northern Children's HospitalNewcastle upon TyneUK
| | - J. D. Edgar
- UKPIN UKPID Registry TeamUKPINLondonUK
- Regional Immunology ServiceThe Royal HospitalsBelfastUK
| | - S. O. Burns
- Department of ImmunologyRoyal Free Hospital, Institute of Immunology and Transplantation, University CollegeLondonUK
| | - M. Thomas
- ImmunologyNHS Greater Glasgow & ClydeGlasgowUK
| | - H. Alachkar
- ImmunologySalford Royal Foundation TrustManchesterUK
| | - M. Buckland
- UKPIN UKPID Registry TeamUKPINLondonUK
- ImmunologySt Bartholomew's HospitalLondonUK
| | | | | | - M. S. Jolles
- Department of ImmunologyUniversity Hospital of WalesCardiffUK
| | - R. Herriot
- ImmunologyAberdeen Royal InfirmaryAberdeenUK
| | - P. D. Arkwright
- Paediatric Allergy and ImmunologyUniversity of ManchesterManchesterManchesterUK
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22
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Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity. Curr Allergy Asthma Rep 2017; 16:55. [PMID: 27401913 DOI: 10.1007/s11882-016-0632-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness.
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23
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Guaní-Guerra E, Jiménez-Romero AI, García-Ramírez UN, Velázquez-Ávalos JM, Martínez-Guzmán E, Sandoval-Ramírez E, Camacho-Meza I. Disease burden for patients with primary immunodeficiency diseases identified at reference hospitals in Guanajuato, Mexico. PLoS One 2017; 12:e0175867. [PMID: 28448570 PMCID: PMC5407621 DOI: 10.1371/journal.pone.0175867] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 03/31/2017] [Indexed: 11/19/2022] Open
Abstract
Background In addition to the deleterious effect on health, there is considerable economic and psychosocial morbidity associated with primary immunodeficiency diseases (PID). Also, the cost of a late diagnosis frequently results in a heavy disease burden on the patient. The objective of this study was to collect and analyze data on patients with PID in the state of Guanajuato in Mexico, to indirectly estimate the burden of the disease. Methods An observational, longitudinal, and comparative study was conducted. A total of 44 patients were included and grouped according to the updated classification of PID. Results The median time elapsed from the onset of symptoms to the reference and diagnosis by a tertiary hospital was of 2.17 (IQR = 6.44) years. Before diagnosis, the number of hospitalizations/year per patient was 0.86 (IQR = 2.28), the number of visit to emergency room/year per patient was 0.92 (IQR = 1.77), the number of doctor’s visits/year per patient was 15 (IQR = 11.25), whereas the school/work absence days per patient were reported in 52.72 (IQR = 56.35) days per year. After diagnosis, 20 patients (45.45%) received IVIG replacement therapy, and all of them presented a significant improvement (p <0.05) in all the mentioned variables. Characteristically, even when patients with PID received IVIG, there was still an important disease burden when comparing them against healthy controls. Complications secondary to PID were detected in 19 patients (43.18%). The reported overall mortality rate was 6.82% (n = 3). Conclusions We were able to indirectly estimate an important disease burden in patients with PID; which is considered to be preventable, at least in part, with effective interventions like health planning, research, collaboration with primary care providers, and generation of policies and practices, in order to improve the quality of life and care of families with PID.
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Affiliation(s)
- Eduardo Guaní-Guerra
- Department of Immunology, Hospital Regional de Alta Especialidad del Bajío, León Guanajuato, México
- Department of Immuno-Alergology, Hospital Aranda de la Parra, León Guanajuato, México
- * E-mail:
| | | | | | | | - Edgar Martínez-Guzmán
- Department of Immunology, Hospital Regional de Alta Especialidad del Bajío, León Guanajuato, México
| | - Eunice Sandoval-Ramírez
- Department of Immuno-Allergology Pediatrics, Hospital Pediátrico de León, León Guanajuato, México
| | - Ignacio Camacho-Meza
- Department of Immuno-Allergology Pediatrics, Hospital Pediátrico de León, León Guanajuato, México
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24
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Ataeinia B, Montazeri A, Tavakol M, Azizi G, Kiaee F, Tavakolinia N, Negahdari B, Mohammadi J, Abolhassani H, Rezaei N, Aghamohammadi A. Measurement of Health-Related Quality of Life in Primary Antibody-Deficient Patients. Immunol Invest 2017; 46:329-340. [PMID: 28358233 DOI: 10.1080/08820139.2016.1258710] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Primary immunodeficiency diseases are a group of disorders that result from a variety of defects of the immune system. Primary antibody deficiencies (PADs) are the most common forms of these disorders. Occurrence of recurrent infections, autoimmune diseases, cancers, and lymphoproliferative disorders is higher in PAD patients. Chronicity of these diseases, delayed diagnosis, inadequate treatment, and treatment side effects may affect the quality of life (QoL) of PAD patients. Evaluating QoL is important for patient care, understanding the burden of these diseases, and finding the patients' major health problems. We investigated the QoL in a group of PAD patients undergoing regular follow-up and treatment at the Children's Medical Center Hospital in Tehran, Iran. METHODS Seventy patients with a diagnosis of PAD in two age groups (younger and older than 18 years) were included. QoL was measured using PedsQL and SF-36 questionnaires. Correlation of demographic, clinical, and immunological parameters with QoL scores was assessed and patients' scores were compared with the normal population, using nonparametric tests of SPSS software. RESULTS Patients expressed significantly reduced scores in some mental and physical components. Patients with longer follow-up periods had higher scores in mental components but physical component scores were still low. There was no significant correlation between sex, age, and disease types with scores. CONCLUSIONS PAD patients had significantly lower scores in mental and physical components compared to normal population. By early diagnosis and long-term follow-up periods, we may be able to prevent complications and help patients to have a better QoL.
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Affiliation(s)
- Bahar Ataeinia
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,b Students' Scientific Research Center (SSRC) , Tehran University of Medical Sciences , Tehran , Iran
| | - Ali Montazeri
- c Iranian Institute for Health Sciences Research , Tehran , Iran
| | - Marzieh Tavakol
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,d Department of Allergy and Clinical Immunology, Shahid Bahonar Hospital , Alborz University of Medical Sciences , Karaj , Iran
| | - Gholamreza Azizi
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,e Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital , Alborz University of Medical Sciences , Karaj , Iran
| | - Fatemeh Kiaee
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Naiimeh Tavakolinia
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Babak Negahdari
- f School of Advanced Technologies in Medicine, Department of Medical Biotechnology , Tehran University of Medical Sciences , Tehran , Iran
| | - Javad Mohammadi
- g Department of Biomedical Engineering, Faculty of New Sciences and Technologies , University of Tehran , Tehran , Iran
| | - Hassan Abolhassani
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,h Division of Clinical Immunology, Department of Laboratory Medicine , Karolinska Institutet at the Karolinska University Hospital Huddinge , Stockholm , Sweden
| | - Nima Rezaei
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.,i Molecular Immunology Research Center, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Asghar Aghamohammadi
- a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
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25
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Azizi G, Ahmadi M, Abolhassani H, Yazdani R, Mohammadi H, Mirshafiey A, Rezaei N, Aghamohammadi A. Autoimmunity in Primary Antibody Deficiencies. Int Arch Allergy Immunol 2016; 171:180-193. [DOI: 10.1159/000453263] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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26
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Schussler E, Beasley MB, Maglione PJ. Lung Disease in Primary Antibody Deficiencies. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2016; 4:1039-1052. [PMID: 27836055 PMCID: PMC5129846 DOI: 10.1016/j.jaip.2016.08.005] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 08/03/2016] [Accepted: 08/22/2016] [Indexed: 01/08/2023]
Abstract
Primary antibody deficiencies (PADs) are the most common form of primary immunodeficiency and predispose to severe and recurrent pulmonary infections, which can result in chronic lung disease including bronchiectasis. Chronic lung disease is among the most common complications of PAD and a significant source of morbidity and mortality for these patients. However, the development of lung disease in PAD may not be solely the result of recurrent bacterial infection or a consequence of bronchiectasis. Recent characterization of monogenic immune dysregulation disorders and more extensive study of common variable immunodeficiency have demonstrated that interstitial lung disease (ILD) in PAD can result from generalized immune dysregulation and frequently occurs in the absence of pneumonia history or bronchiectasis. This distinction between bronchiectasis and ILD has important consequences in the evaluation and management of lung disease in PAD. For example, treatment of ILD in PAD typically uses immunomodulatory approaches in addition to immunoglobulin replacement and antibiotic prophylaxis, which are the stalwarts of bronchiectasis management in these patients. Although all antibody-deficient patients are at risk of developing bronchiectasis, ILD occurs in some forms of PAD much more commonly than in others, suggesting that distinct but poorly understood immunological factors underlie the development of this complication. Importantly, ILD can have earlier onset and may worsen survival more than bronchiectasis. Further efforts to understand the pathogenesis of lung disease in PAD will provide vital information for the most effective methods of diagnosis, surveillance, and treatment of these patients.
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Affiliation(s)
- Edith Schussler
- Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Mary B Beasley
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Paul J Maglione
- Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
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27
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Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, Rezaei N, Ochs HD, Aghamohammadi A. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol 2016; 13:101-115. [DOI: 10.1080/1744666x.2016.1224664] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Gholamreza Azizi
- Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Hassan Abolhassani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Mohammad Hosein Asgardoon
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Iranian Student Society for Immunodeficiencies, Student’s Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Tina Alinia
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Yazdani
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javad Mohammadi
- Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hans D. Ochs
- Seattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - Asghar Aghamohammadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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28
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Harsini S, Ziaee V, Tahghighi F, Mahmoudi M, Rezaei A, Soltani S, Sadr M, Moradinejad MH, Aghighi Y, Rezaei N. Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus. Allergol Immunopathol (Madr) 2016; 44:422-6. [PMID: 27255473 DOI: 10.1016/j.aller.2015.12.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 11/22/2015] [Accepted: 12/03/2015] [Indexed: 12/22/2022]
Abstract
PURPOSE Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. MATERIALS AND METHODS The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at -330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. RESULTS Results of the analysed data revealed a negative allelic association for JSLE in IL-2 -330/T (P=0.02), as well as a positive allelic association for IL-2 -330/G (P=0.02). IL-2 GG genotype (-330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (-330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (-330, +166) GT haplotype was significantly higher in the patient group (P<0.001). CONCLUSION IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE.
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Affiliation(s)
- S Harsini
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - V Ziaee
- Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - F Tahghighi
- Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - M Mahmoudi
- School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - A Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - S Soltani
- Molecular Immunology Research Center and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - M Sadr
- Molecular Immunology Research Center and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - M H Moradinejad
- Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Y Aghighi
- Department of Pediatrics, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - N Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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Nabavi M, Arshi S, Bemanian M, Aghamohammadi A, Mansouri D, Hedayat M, Nateghian A, Noorbakhsh S, Ehsanipour F, Faranoush M, Shakeri R, Mesdaghi M, Taghvaei B, Ghalebaghi B, Babaie D, Bahrami A, Fallahpour M, Esmaeilzadeh H, Ali Hamidieh A, Rekabi M, Ahmadian J, Eslami N, Shokri S, Afshar M, Jalali F, Akbarpour N, Molatefi R, Rezaei N. Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre. Allergol Immunopathol (Madr) 2016; 44:322-30. [PMID: 26803694 DOI: 10.1016/j.aller.2015.09.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 09/27/2015] [Accepted: 09/30/2015] [Indexed: 11/27/2022]
Abstract
PURPOSE The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.
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Jiang T, Li Z, Zhang Q. Advances in neonatal screening for primary immune deficiencies. Exp Ther Med 2016; 11:1542-1544. [PMID: 27168770 PMCID: PMC4840582 DOI: 10.3892/etm.2016.3119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 03/01/2016] [Indexed: 01/10/2023] Open
Abstract
The congenital disorders of immune competence are known as primary immunodeficiencies (PID) and are mainly characterized by a pathological susceptibility to infection. These infections are mostly of time repetitive and drug resistant in nature. The number of infected infants has reached over 200 and is on the increase. Additionally, clinical severity of the disease has been confirmed to be extensive. The increasing number of these severe PIDs is due to the lack of specific as well as efficient management avenues. New assays and concepts for newborn screening of severe primary immune deficiencies are being explored and the present review focused on these new upcoming strategies for improved screening of neonates.
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Affiliation(s)
- Tingting Jiang
- Department of Neonatology, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221002, P.R. China
| | - Zhenguang Li
- Department of Neonatology, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221002, P.R. China
| | - Qiuli Zhang
- Department of Neonatology, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221002, P.R. China
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Abolhassani H, Asgardoon MH, Rezaei N, Hammarstrom L, Aghamohammadi A. Different brands of intravenous immunoglobulin for primary immunodeficiencies: how to choose the best option for the patient? Expert Rev Clin Immunol 2015; 11:1229-43. [DOI: 10.1586/1744666x.2015.1079485] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Verma N, Grimbacher B, Hurst JR. Lung disease in primary antibody deficiency. THE LANCET RESPIRATORY MEDICINE 2015; 3:651-60. [PMID: 26188881 DOI: 10.1016/s2213-2600(15)00202-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 05/11/2015] [Accepted: 05/11/2015] [Indexed: 12/25/2022]
Abstract
This Review summarises current knowledge on the pulmonary manifestations of primary antibody deficiency (PAD) syndromes in adults. We describe the major PAD syndromes, with a particular focus on common variable immunodeficiency (CVID). Respiratory infection is a common presenting feature of PAD syndromes. Respiratory complications are frequent and responsible for much of the morbidity and mortality associated with these syndromes. Respiratory complications include acute infections, the sequelae of infection (eg, bronchiectasis), non-infectious immune-mediated manifestations (notably the development of granulomatous-lymphocytic interstitial lung disease in CVID), and an increased risk of lymphoma. Although minor abnormalities are detectable in the lungs of most patients with CVID by CT scanning, not all patients develop lung complications. Mechanisms associated with the maintenance of lung health versus lung disease, and the development of bronchiectasis versus immune-mediated complications, are now being dissected. We review the investigation, treatment, and management strategies for PAD syndromes, and include key research questions relating to both infectious and non-infectious complications of PAD in the lung.
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Affiliation(s)
- Nisha Verma
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK
| | - Bodo Grimbacher
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK; Centre for Chronic Immunodeficiency, Medical Centre, University Hospital Freiburg, Freiburg, Germany
| | - John R Hurst
- UCL Respiratory, University College London, London, UK.
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Akaba T, Kondo M, Toriyama M, Kubo A, Hara K, Yamada T, Yoshinaga K, Tamaoki J. Common variable immunodeficiency diagnosed during the treatment of bronchial asthma: Unusual cause of wheezing. Respir Med Case Rep 2015; 16:41-4. [PMID: 26744651 PMCID: PMC4681971 DOI: 10.1016/j.rmcr.2015.07.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 07/07/2015] [Accepted: 07/08/2015] [Indexed: 11/20/2022] Open
Abstract
Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency in adults and children. We herein report a case of CVID, who was misdiagnosed with asthma due to wheezing episodes and relatively late onset. A 51-year-old woman had suffered from recurrent upper and lower airway infection for recent 2 years. She repeated wheezing attacks and was treated as asthma exacerbation triggered by infection. She was referred to our hospital for investigation and treatment. Lung function tests showed no reversibility of FEV1 by β-adrenergic agonist, but the increase of V50/V25. Chest CT showed slight to moderate bronchial wall thickening and bronchiectasis. After that, she suffered from pneumonia with wheezing attacks twice a month, and immunodeficiency was strongly suspected. Her blood tests showed marked decreases of all classes of immunoglobulin and nearly lack of memory B cells, NKT cells and plasmacytoid dendritic cells. She was diagnosed with CVID, and was treated with replacement of gammaglobulin. Thereafter, her wheezing episodes with infection were remarkably improved. Because the delay of diagnosis with CVID likely causes poor mortality and morbidity, a possibility of CVID should be considered in patients with frequent asthma-like symptoms due to recurrent airway infection.
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Affiliation(s)
- Tomohiro Akaba
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Mitsuko Kondo
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Midori Toriyama
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Ayako Kubo
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kaori Hara
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Takeshi Yamada
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kentaro Yoshinaga
- Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Jun Tamaoki
- First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan
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Qi Q, Wang W, Li T, Zhang Y, Li Y. Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population: A prospective study. Respirology 2015; 20:917-24. [PMID: 26096854 DOI: 10.1111/resp.12574] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 03/15/2015] [Accepted: 03/17/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVE Bronchiectasis is a chronic respiratory disease with diverse causes that may differ in clinical features and thus treatment options. However, few large-scale studies on the aetiology of bronchiectasis are currently available. This study aims to determine aetiology and clinical features of bronchiectasis in a Chinese Han population. METHODS This prospective study enrolled adult patients diagnosed with bronchiectasis as confirmed by high-resolution computed tomography at five general hospitals in Shandong from January 2010 to August 2014. Causes of bronchiectasis were sought by analysis of clinical history and auxiliary examinations (including serum immunoglobulin determination, saccharin test, Aspergillus skin prick test, autoantibody detection and electronic bronchoscopy). RESULTS A total of 476 adult patients with bronchiectasis were included, and all patients were of Chinese Han ethnicity. Idiopathic (66.0%) was the most common cause, followed by post-tuberculosis (16.0%). Other uncommon causes included post-infective (3.8%), immunodeficiency (3.8%), allergic bronchopulmonary aspergillosis (4.0%), rheumatic diseases (4.4%) and primary ciliary dyskinesia (0.9%). Patients with post-tuberculosis bronchiectasis had a higher frequency of upper lobe involvement (P < 0.05). Cylindrical bronchiectasis was the most common type of all causes, with varicose bronchiectasis occurring more frequently in post-tuberculosis bronchiectasis and allergic bronchopulmonary aspergillosis (P < 0.05). However, patients with different causes did not differ in lung function and sputum isolation rate of Pseudomonas aeruginosa (P > 0.05). CONCLUSIONS In a Chinese Han population in Shandong, idiopathic bronchiectasis is the most common form of bronchiectasis followed by post-tuberculosis bronchiectasis. Patients with different causes differ in distribution and pattern of bronchiectasis on computed tomography.
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Affiliation(s)
- Qian Qi
- Department of Pulmonary Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Wen Wang
- Department of Pulmonary Disease, Chengdu Second People's Hospital, Chengdu, China
| | - Tao Li
- Department of Pulmonary Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Yan Zhang
- Department of Pulmonary Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Yu Li
- Department of Pulmonary Disease, Qilu Hospital of Shandong University, Jinan, China
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Milliron B, Henry TS, Veeraraghavan S, Little BP. Bronchiectasis: Mechanisms and Imaging Clues of Associated Common and Uncommon Diseases. Radiographics 2015; 35:1011-30. [PMID: 26024063 DOI: 10.1148/rg.2015140214] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Bronchiectasis is permanent irreversible dilatation of the airways and occurs in a variety of pathologic processes. Recurrent infection and inflammation and the resulting chemical and cellular cascade lead to permanent architectural changes in the airways. Bronchiectasis can confer substantial potential morbidity, usually secondary to recurrent infection. In severe cases of bronchiectasis, massive hemoptysis can lead to death. Thin-section computed tomography is the most sensitive imaging modality for the detection of bronchiectasis; findings include bronchial diameter exceeding that of the adjacent pulmonary artery and lack of normal tapering of terminal bronchioles as they course toward the lung periphery. The authors will review various causes of bronchiectasis, including common causes, such as recurrent infection or aspiration, and uncommon causes, such as congenital immunodeficiencies and disorders of cartilage development. The authors will also present an approach emphasizing the distribution (apical versus basal and central versus peripheral) and concomitant findings, such as nodules, cavities, and/or lymphadenopathy, that can assist in narrowing the differential diagnosis. Although an adequate understanding of these underlying causes in conjunction with their specific imaging appearances will allow radiologists to more confidently determine the process causing this common radiologic finding, clinical history and patient demographic characteristics play an integral role in determining a pertinent and concise differential diagnosis.
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Affiliation(s)
- Bethany Milliron
- From the Department of Radiology and Imaging Sciences, Division of Cardiothoracic Imaging (B.M., T.S.H., B.P.L.), and Division of Pulmonary, Allergy, and Critical Care Medicine (S.V.), Emory University School of Medicine, 1364 Clifton Rd NE, Room D125A, Atlanta, GA 30322
| | - Travis S Henry
- From the Department of Radiology and Imaging Sciences, Division of Cardiothoracic Imaging (B.M., T.S.H., B.P.L.), and Division of Pulmonary, Allergy, and Critical Care Medicine (S.V.), Emory University School of Medicine, 1364 Clifton Rd NE, Room D125A, Atlanta, GA 30322
| | - Srihari Veeraraghavan
- From the Department of Radiology and Imaging Sciences, Division of Cardiothoracic Imaging (B.M., T.S.H., B.P.L.), and Division of Pulmonary, Allergy, and Critical Care Medicine (S.V.), Emory University School of Medicine, 1364 Clifton Rd NE, Room D125A, Atlanta, GA 30322
| | - Brent P Little
- From the Department of Radiology and Imaging Sciences, Division of Cardiothoracic Imaging (B.M., T.S.H., B.P.L.), and Division of Pulmonary, Allergy, and Critical Care Medicine (S.V.), Emory University School of Medicine, 1364 Clifton Rd NE, Room D125A, Atlanta, GA 30322
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Ebadi M, Aghamohammadi A, Rezaei N. Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics. Expert Rev Clin Immunol 2014; 11:117-39. [DOI: 10.1586/1744666x.2015.995096] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Aghamohammadi A, Abolhassani H, Latif A, Tabassomi F, Shokuhfar T, Torabi Sagvand B, Shahinpour S, Mirminachi B, Parvaneh N, Movahedi M, Gharagozlou M, Sherkat R, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Cheraghi T, Eslamian MH, Khalili A, Kalantari N, Shafiei A, Dabbaghzade A, Khayatzadeh A, Ebrahimi M, Razavinejad D, Bazregari S, Ebrahimi M, Ghaffari J, Bemanian MH, Behniafard N, Kashef S, Mohammadzadeh I, Hammarström L, Rezaei N. Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients. Expert Rev Clin Immunol 2014; 10:1405-17. [DOI: 10.1586/1744666x.2014.958469] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, Yel L, Sullivan KE. Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol 2014; 34:627-32. [PMID: 24909997 DOI: 10.1007/s10875-014-0056-x] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 05/09/2014] [Indexed: 12/30/2022]
Abstract
PURPOSE In the past, XLA was described as associated with several inflammatory conditions, but with adequate immune globulin treatment, these are presumed to have diminished. The actual prevalence is not known. METHODS A web-based patient survey was conducted December 2011- February 2012. Respondents were recruited from the Immune Deficiency Foundation (IDF) patient database, online patient discussion forums and physician recruitment of patients. The questionnaire was developed jointly by IDF and by members of the USIDNET-XLA Disease Specific Working Group. Information regarding inflammatory conditions in patients with XLA was also obtained from the United States Immune Deficiency Network (USIDNET) Registry. RESULTS Based on 128 unique patient survey responses, the majority of respondents (69%) reported having at least one inflammatory symptom, with 53% reporting multiple symptoms. However, only 28% had actually been formally diagnosed with an inflammatory condition. Although 20% reported painful joints and 11% reported swelling of the joints, only 7% were given a diagnosis of arthritis. Similarly, 21% reported symptoms of chronic diarrhea and 17% reported abdominal pain, however only 4% had been diagnosed with Crohn's disease. Data from the USIDNET Registry on 149 patients with XLA, revealed that 12% had pain, swelling or arthralgias, while 18% had been diagnosed with arthritis. Similarly, 7% of these patients had abdominal pain and 9% chronic diarrhea. CONCLUSIONS Although patients with XLA are generally considered to have a low risk of autoimmune or inflammatory disease compared to other PIDD cohorts, data from this patient survey and a national registry indicate that a significant proportion of patients with XLA have symptoms that are consistent with a diagnosis of arthritis, inflammatory bowel disease or other inflammatory condition. Documented diagnoses of inflammatory diseases were less common but still increased over the general population. Additional data is required to begin implementation of careful monitoring of patients with XLA for these conditions. Early diagnosis and proper treatment may optimize clinical outcomes for these patients.
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Affiliation(s)
- Vivian P Hernandez-Trujillo
- Division of Allergy and Immunology, Department of Pediatrics, Miami Children's Hospital, 3100 SW 62 Avenue, Miami, FL, 33155, USA,
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Latif AH, Tabassomi F, Abolhassani H, Hammarström L. Molecular diagnosis of primary immunodeficiency diseases in a developing country: Iran as an example. Expert Rev Clin Immunol 2014; 10:385-96. [DOI: 10.1586/1744666x.2014.880654] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr 2014; 2:77. [PMID: 25121077 PMCID: PMC4110629 DOI: 10.3389/fped.2014.00077] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 07/07/2014] [Indexed: 12/17/2022] Open
Abstract
Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of immune system are decreased, missing, or of non-appropriate function. These diseases affect the development, function, or morphology of the immune system. The group of PID comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. Their clinical presentation and complications depend on the type of defects and there is a great variability in the relationship between genotypes and phenotypes. A variation of clinical presentation across various age categories is also presented and children could widely differ from adult patients with PID. Respiratory symptoms and complications present a significant cause of morbidity and also mortality among patients suffering from different forms of PIDs and they are observed both in children and adults. They can affect primarily either upper airways (e.g., sinusitis and otitis media) or lower respiratory tract [e.g., pneumonia, bronchitis, bronchiectasis, and interstitial lung diseases (ILDs)]. The complications from lower respiratory tract are usually considered to be more important and also more specific for PIDs and they determinate patients' prognosis. The spectrum of the causal pathogens usually demonstrates typical pattern characteristic for each PID category. The respiratory signs of PIDs can be divided into infectious (upper and lower respiratory tract infections and complications) and non-infectious (ILDs, bronchial abnormalities - especially bronchiectasis, malignancies, and benign lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at least slow down the development and course of respiratory complications of PIDs.
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Affiliation(s)
- Milos Jesenak
- Center for Diagnosis and Treatment of Primary Immunodeficiencies, Department of Pediatrics, Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia
| | - Peter Banovcin
- Center for Diagnosis and Treatment of Primary Immunodeficiencies, Department of Pediatrics, Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia
| | - Barbora Jesenakova
- Center for Diagnosis and Treatment of Primary Immunodeficiencies, Department of Pediatrics, Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia
| | - Eva Babusikova
- Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava , Martin , Slovakia
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Activity, severity and impact of respiratory disease in primary antibody deficiency syndromes. J Clin Immunol 2013; 34:68-75. [PMID: 24136152 DOI: 10.1007/s10875-013-9942-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 09/30/2013] [Indexed: 01/22/2023]
Abstract
PURPOSE Some patients with primary antibody deficiency (PAD) syndromes develop bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico-pathophysiological relationships exist between exacerbation frequency, lung function, health-status, infection and inflammation. It is not known whether such relationships are present in PAD. It is also not known how local and systemic inflammation in PAD compares with that in immunocompetent (non-PAD) bronchiectasis patients. METHOD We assessed symptoms, exacerbation frequency, health-status, lung function, CT, airway and systemic inflammation and infection in 33 PAD patients and 20 immunocompetent controls with bronchiectasis. RESULTS Despite less severe airflow obstruction, PAD patients had similar health-status impairment and greater airway (sputum log10 IL-6 2.71 vs. 1.81 pg/ml, p = 0.001) and greater systemic inflammation than immunocompetent bronchiectasis controls (serum log10 CRP 0.77 vs. 0.36 mg/l, p = 0.001). In PAD, cross-sectional markers of disease severity (CT and lung function) did not relate to inflammatory markers of disease activity, however there was a relationship between FEV1 decline rate and systemic inflammation (IL-6; r = 0.42, p = 0.036) and the magnitude of the systemic inflammatory response was related to that in the airway. Correlation between generic SF36 and respiratory SGRQ questionnaires (r = -0.79, p < 0.001) suggests that much health-status impairment in PAD relates to respiratory involvement. Health-status was associated with dyspnoea (rho = 0.77, p < 0.001), respiratory infection frequency (rho = 0.48, p = 0.016), lung function (FEV1: r = -0.60, p = 0.001) and rate of lung function decline (r = 0.41, p = 0.047). CONCLUSION The major findings of this analysis are that in patients with PAD, cross-sectional markers of disease severity such as lung function and CT extent of disease do not reflect disease activity as assessed by airway and systemic inflammation. In addition, there is a relationship between the rate of progression of lung disease and the severity of the systemic inflammatory response which itself is related to that in the airway. Much of the quality of life impact in PAD relates to respiratory involvement, specifically the severity of airflow obstruction, respiratory exacerbation frequency and dyspnoea. Finally, patients with PAD had greater airway and systemic inflammation than a control population with non-PAD bronchiectasis which may suggest a dysregulated airway immune response.
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Maglione PJ, Ko HM, Beasley MB, Strauchen JA, Cunningham-Rundles C. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency. J Allergy Clin Immunol 2013; 133:535-42. [PMID: 24131823 DOI: 10.1016/j.jaci.2013.08.022] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Revised: 07/09/2013] [Accepted: 08/16/2013] [Indexed: 01/07/2023]
Abstract
BACKGROUND Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. OBJECTIVE We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. METHODS We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. RESULTS In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. CONCLUSION Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia.
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Affiliation(s)
- Paul J Maglione
- Immunology Institute, Mount Sinai School of Medicine, New York, NY; Department of Medicine, Mount Sinai School of Medicine, New York, NY
| | - Huaibin M Ko
- Department of Pathology, Mount Sinai School of Medicine, New York, NY
| | - Mary B Beasley
- Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pathology, Mount Sinai School of Medicine, New York, NY
| | - James A Strauchen
- Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pathology, Mount Sinai School of Medicine, New York, NY
| | - Charlotte Cunningham-Rundles
- Immunology Institute, Mount Sinai School of Medicine, New York, NY; Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pediatrics, Mount Sinai School of Medicine, New York, NY.
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Truong T. The overlap of bronchiectasis and immunodeficiency with asthma. Immunol Allergy Clin North Am 2012; 33:61-78. [PMID: 23337065 DOI: 10.1016/j.iac.2012.10.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Bronchiectasis should be considered as a differential diagnosis for, as well as a comorbidity in, patients with asthma, especially severe or long-standing asthma. Chronic airway inflammation is thought to be the primary cause, as with chronic or recurrent pulmonary infection and autoimmune conditions that involve the airways. Consequently, immunodeficiencies with associated increased susceptibility to respiratory tract infections or chronic inflammatory airways also increase the risk of developing bronchiectasis. Chronic bronchiectasis is associated with impaired mucociliary clearance and increased bronchial secretions, leading to airway obstruction and airflow limitation, which can lead to exacerbation of underlying asthma or increased asthma symptoms.
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Affiliation(s)
- Tho Truong
- Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA.
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Aghamohammadi A, Abolhassani H, Hirbod-Mobarakeh A, Ghassemi F, Shahinpour S, Behniafard N, Naghibzadeh G, Imanzadeh A, Rezaei N. The Uncommon Combination of Common Variable Immunodeficiency, Macrophage Activation Syndrome, and Cytomegalovirus Retinitis. Viral Immunol 2012; 25:161-5. [DOI: 10.1089/vim.2011.0060] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Asghar Aghamohammadi
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hassan Abolhassani
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Armin Hirbod-Mobarakeh
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Fariba Ghassemi
- Eye Research Center, Farabi Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shervin Shahinpour
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasrin Behniafard
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazal Naghibzadeh
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Imanzadeh
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Molecular Immunology Research Center, and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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46
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Aghamohammadi A, Abolhassani H, Eibl MM, Espanol T, Kanegane H, Miyawaki T, Mohammadinejad P, Pourhamdi S, Wolf HM, Parvaneh N, Al-Herz W, Durandy A, Stiehm ER, Plebani A. Predominantly Antibody Deficiency. CLINICAL CASES IN PRIMARY IMMUNODEFICIENCY DISEASES 2012:113-192. [DOI: 10.1007/978-3-642-31785-9_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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