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Ren ZF, Xiong RC, Wang LL, Chen ZH, Chen R, Liu ZF. The well-defined antiphospholipid syndrome induced by COVID-19: a rare case report and review of the literature. Thromb J 2024; 22:99. [PMID: 39516860 PMCID: PMC11549801 DOI: 10.1186/s12959-024-00669-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
COVID-19 may induce a state of hypercoagulability, particularly in critically ill patients, for reasons that remain unknown. Numerous studies have identified the presence of antiphospholipid antibodies in patients with COVID-19; however, the definitive diagnosis of antiphospholipid syndrome continues to pose challenges. Here, we present the case of a patient infected with SARS-CoV-2 who developed life-threatening severe thrombocytopenia, profound anaemia, acute pulmonary hypertension, right ventricular failure, and renal insufficiency. Laboratory investigations revealed significantly elevated levels of antiphospholipid antibodies. We conducted a one-year follow-up study with blood sampling performed every 12 weeks. The patient exhibited persistent high titres of antiphospholipid antibodies and ongoing renal dysfunction necessitating daily oral warfarin antithrombotic therapy. Antiphospholipid syndrome is a complex clinical condition that poses challenges for clinicians, particularly in critically ill patients, and is often associated with delayed and inaccurate diagnosis and treatment. Therefore, we extensively reviewed the literature and international guidelines to conduct a comprehensive analysis of the aetiology, pathogenesis, and treatment strategies of APS. We hope this work will provide a valuable reference for health care professionals.
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Affiliation(s)
- Zong-Fang Ren
- Department of Medical Critical Care Medicine, General Hospital of Southern Theatre Command of Peoples Liberation Army, Guangzhou, 510010, China
- Department of Critical Care Medicine, the Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, China
| | - Ri-Cheng Xiong
- Department of Medical Critical Care Medicine, General Hospital of Southern Theatre Command of Peoples Liberation Army, Guangzhou, 510010, China
| | - Ling-Ling Wang
- Department of Medical Critical Care Medicine, General Hospital of Southern Theatre Command of Peoples Liberation Army, Guangzhou, 510010, China
| | - Zhi-Huang Chen
- Department of Chinese Medicine, General Hospital of Southern Theater Command of Peoples Liberation Army, Guangzhou, 510010, China
| | - Rui Chen
- Department of Medical Critical Care Medicine, General Hospital of Southern Theatre Command of Peoples Liberation Army, Guangzhou, 510010, China
| | - Zhi-Feng Liu
- Department of Medical Critical Care Medicine, General Hospital of Southern Theatre Command of Peoples Liberation Army, Guangzhou, 510010, China.
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Salimi M, Mirghaderi P, Mosalamiaghili S, Mohammadi A, Salimi A. Joint replacement and human immunodeficiency virus. World J Virol 2023; 12:1-11. [PMID: 36743660 PMCID: PMC9896588 DOI: 10.5501/wjv.v12.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/19/2022] [Accepted: 12/08/2022] [Indexed: 01/18/2023] Open
Abstract
The incidence of human immunodeficiency virus (HIV)-infected cases that need total joint replacement (TJR) is generally rising. On the other hand, modern management of HIV-infected cases has enabled them to achieve longevity while increasing the need for arthroplasty procedures due to the augmented dege-nerative joint disease and fragility fractures, and the risk of osteonecrosis. Although initial investigations on joint replacement in HIV-infected cases showed a high risk of complications, the recent ones reported acceptable outcomes. It is a matter of debate whether HIV-infected cases are at advanced risk for adverse TJR consequences; however, the weak immune profile has been associated with an increased probability of complications. Likewise, surgeons and physicians should be aware of the complication rate after TJR in HIV-infected cases and include an honest discussion of the probable unwelcoming complication with their patients contemplating TJR. Therefore, a fundamental review and understanding of the interaction of HIV and arthroplasty are critical.
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Affiliation(s)
- Maryam Salimi
- Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz 71936-13311, Iran
| | - Peyman Mirghaderi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran 7138433608, Iran
| | | | - Ali Mohammadi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7136587666, Iran
| | - Amirhossein Salimi
- Department of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 7156893040, Iran
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Schapkaitz E, Jacobson BF, Libhaber E. Pregnancy Related Venous Thromboembolism-Associated with HIV Infection and Antiretroviral Therapy. Semin Thromb Hemost 2022; 49:355-363. [PMID: 36055274 DOI: 10.1055/s-0042-1754391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Human immunodeficiency virus (HIV) infection in pregnancy is associated with substantial morbidity and mortality. Improved access to effective antiretroviral therapy (ART) has shifted the spectrum of pregnancy-related complications among HIV-infected pregnant women. In addition to placental vascular complications and preterm delivery, increased rates of venous thromboembolism (VTE) have been described. HIV infection is characterized by immune activation, inflammation, and endothelial dysfunction, which contribute to the activation of coagulation and its prothrombotic consequences. Indeed, activated coagulation factors have been reported to be increased and natural anticoagulants reduced in HIV. Several mechanisms for this persistent prothrombotic balance on ART have been identified. These may include: co-infections, immune recovery, and loss of the gastrointestinal mucosal integrity with microbial translocation. In addition to the direct effects of HIV and ART, traditional venous and obstetric risk factors also contribute to the risk of VTE. A research priority has been to understand the mechanisms of VTE in HIV-infected pregnant women receiving suppressive ART and to translate this into HIV-specific thromboprophylaxis recommendations. Management requires a multidisciplinary approach and further studies are indicated to guide the prevention and management of pregnancy-associated VTE in this population. The current review describes the epidemiology, mechanisms, and management of VTE in HIV-infected women in pregnancy and the postpartum period.
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Affiliation(s)
- Elise Schapkaitz
- Department of Molecular Medicine and Hematology, University of Witwatersrand, Johannesburg, South Africa
| | - Barry F Jacobson
- Department of Molecular Medicine and Hematology, University of Witwatersrand, Johannesburg, South Africa
| | - Elena Libhaber
- Department of Research Methodology and Statistics, University of Witwatersrand, Johannesburg, South Africa
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Anticardiolipin Autoantibodies as Useful Biomarkers for the Prediction of Mortality in Septic Patients. J Immunol Res 2022; 2022:9775111. [PMID: 35685432 PMCID: PMC9174012 DOI: 10.1155/2022/9775111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 03/30/2022] [Accepted: 05/11/2022] [Indexed: 11/17/2022] Open
Abstract
Background. The detection of antiphospholipid antibodies (aPL) is of interest because of their importance in the pathogenesis of arterial or venous thrombosis. They could be a “second hit” of an inflammatory event such as infection. The aim of our study was to assess the performance of antiphospholipid antibody biomarker to predict in-hospital mortality in intensive care unit (ICU) septic patients. Methods. We conducted a prospective single-center observational study including consecutive critically ill septic adults admitted to the intensive care unit. Clinical and laboratory data including enzyme-linked immunosorbent assay for antiphospholipid antibodies (anticardiolipin (aCL), antiphosphatidylserine (aPS)) were obtained. Blood samples were collected on days 1, 3, 5, 8, and 10 of hospitalization. The primary study endpoint was ICU mortality defined as death before ICU discharge. Secondary end points included correlation between SOFA score and biological parameters. Results. A total of 53 patients were enrolled. 18.8% of patients were aPL positive. In-hospital mortality rate was 60%. Multivariate analysis showed that age and aCL at days 3 and 5 along with SOFA at day 3 were independent outcome predictors. A significant positive correlation existed between SOFA at days 3, 5, and 8 and antiphospholipid antibody concentrations. Conclusions. Our data showed that antiphospholipid was useful biomarkers for the prediction of mortality in critically ill septic patients. We found a positive correlation between SOFA score and antiphospholipid antibodies.
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Schapkaitz E, Libhaber E, Jacobson BF, Gerber A, Rhemtula H, Büller HR. Profile of antiphospholipid antibodies in HIV-infected and HIV-uninfected women with a history of thrombosis. Int J Lab Hematol 2022; 44:635-642. [PMID: 35132770 DOI: 10.1111/ijlh.13805] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/14/2022] [Accepted: 01/22/2022] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Increased antiphospholipid antibodies (aPL) have been described in human immunodeficiency virus (HIV) infection. However, the association between aPL and the increased risk of thrombosis in HIV requires further clarification. METHODS We reviewed the medical records of 215 consecutive women with a history of thrombosis and/or obstetric complications (158 HIV-uninfected and 57 HIV-infected) between July 2017 and March 2021. Participants (n = 215) without clinical criteria manifestations for antiphospholipid syndrome were included as matched controls. Testing for lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2-glycoprotein1 (aβ2GP1) IgM and IgG was performed. RESULTS Thirty-two (10.1%) HIV-uninfected and 15 (13.2%) HIV-infected participants were positive at baseline for one of the five criteria aPL, with no statistically significant difference. The profile of the HIV-infected participants with thrombosis (n = 11) included LAC in 15.8%, aCL IgG in 3.5% and aβ2GP1 IgG in 1.8%. In contrast, the HIV-infected controls (n = 4), included aCL IgM in 1.8% and aβ2GP1 IgM in 5.3%. Only LAC was significantly associated with thrombosis (p < 0.003). On repeat testing, in a HIV-infected sub-population, 2/7 with thrombosis were positive, while 3/3 controls tested negative. CONCLUSION In contrast to earlier reports, the prevalence and expression of aPL in HIV-infected women with a history of thrombosis in the present study, in the era of antiretroviral therapy, were similar to HIV-uninfected women. Baseline LAC positivity was associated with a significantly increased risk for thrombosis in HIV. Future studies are recommended to explore additional coagulation abnormalities in HIV.
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Affiliation(s)
- Elise Schapkaitz
- Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of Witwatersrand Medical School, Johannesburg, South Africa
| | - Elena Libhaber
- HS Research Office and School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand Medical School, Johannesburg, South Africa
| | - Barry F Jacobson
- Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of Witwatersrand Medical School, Johannesburg, South Africa
| | - Annika Gerber
- Department of Obstetrics, Faculty of Health Sciences, University of Witwatersrand Medical School, Johannesburg, South Africa
| | - Haroun Rhemtula
- Department of Obstetrics, Faculty of Health Sciences, University of Witwatersrand Medical School, Johannesburg, South Africa
| | - Harry R Büller
- Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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Analysis of the Coagulation Profile in Children with HIV Infection-Effect of Disease and Anti Retroviral Therapy. Indian J Hematol Blood Transfus 2022; 38:132-137. [PMID: 35125721 PMCID: PMC8804129 DOI: 10.1007/s12288-021-01440-x] [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: 01/13/2021] [Accepted: 04/25/2021] [Indexed: 01/03/2023] Open
Abstract
The pathogenesis of hypercoagulability in HIV infection is multifactorial and usually more than one factor is responsible for a thromboembolic episode. The present study was conducted to evaluate the effect of HIV infection and antiretroviral therapy on various coagulation parameters in paediatric patients. Forty two newly diagnosed paediatric patients with HIV infection who were enrolled at the Anti-Retro viral Therapy (ART) centre of Kalawati Saran Children's Hospital were included in the study. The patients were grouped into 4 clinical stages according to the WHO clinical staging of HIV disease. Coagulation tests [PT, aPTT, fibrinogen, D-Dimer and coagulation inhibitors i.e. Protein C (PC), Protein S (PS) and antithrombin III (AT III), Lupus anticoagulant (LA) and Anti phospholipid antibody (APLA)] were performed in all the patients at the time of diagnosis and repeated after 6 months. All the patients were started on antiretroviral therapy within 2 months of their diagnosis. At the time of diagnosis, prolonged PT and aPTT were observed in 30.9% and 23% of the cases respectively. Hyperfibinogenemia was seen in 11.9% of patients. D-Dimer was raised in 83.3% of patients. PS, PC & AT activities were reduced in 90.4%, 42.8% & 11.9% of cases respectively. A reduction in the PC and AT activity was seen from clinical stage 1 to 4, but the change was not statistically significant. On follow up after 6 months, a statistically significant reduction in the level of fibrinogen and D-Dimer was seen. Even though there was improvement in the activity of all the coagulation inhibitor after 6 months, statistically significant improvement was seen only for PS. The current study shows that HIV produces a hypercoagulable state in children. Raised d-dimer level and deficiency of natural anticoagulants contribute to the thrombophilic state.
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Dong RJ, Lei SY, Li J, Yang XP, Li YY, Zhang YG. Thrombotic antiphospholipid syndrome in a child with human immunodeficiency virus: a rare case report. Thromb J 2021; 19:20. [PMID: 33766024 PMCID: PMC7992315 DOI: 10.1186/s12959-021-00273-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 03/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disorder induced by antiphospholipid antibodies, which occurs exceedingly rarely in pediatric population and even more rarely reported in HIV positive children. A case of 11 years old boy had a sudden onset of swelling in his left lower leg along with pain which were worsening gradually. Initially, topical ointment was applied for 1 month which were ineffective in reducing pain and swelling. Instead, the symptoms were aggravated and suddenly spread to the proximal thigh, accompanied by dyskinesia of left lower leg. Both color doppler ultrasonography and vascular CT scan of left lower leg revealed deep venous thrombosis. His serum anti-phospholipid antibodies (aPLs) were tested positive. He was a known case of HIV virological failure with substantial HIV viral load (VL) despite receiving regular antiretroviral therapy (ART). His symptoms improved after giving aggressive antithrombotic and high dose corticosteroid treatments. CONCLUSION When pediatric patients develop thrombotic disease, APS also needs to be ruled out. The autoantibodies levels should be routinely tested to look for recurrent thrombosis in children with HIV/AIDS.
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Affiliation(s)
- Rong-Jing Dong
- Yunnan Provincial Hospital of Infectious Disease/Yunnan AIDS Care Center, Kunming, 650301, China.,Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Su-Yun Lei
- Yunnan Provincial Hospital of Infectious Disease/Yunnan AIDS Care Center, Kunming, 650301, China
| | - Jun Li
- College of Pharmaceutical Sciences, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, China
| | - Xin-Ping Yang
- Yunnan Provincial Hospital of Infectious Disease/Yunnan AIDS Care Center, Kunming, 650301, China
| | - Yu-Ye Li
- Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
| | - Yun-Gui Zhang
- Yunnan Provincial Hospital of Infectious Disease/Yunnan AIDS Care Center, Kunming, 650301, China.
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Hamadé A, Woehl B, Harzallah I, Talbot M, Tousch J, Jambert L. Antiphospholipid antibodies in patients with coronavirus disease 2019 infection hospitalized in conventional unit. Blood Coagul Fibrinolysis 2021; 32:73-79. [PMID: 33273262 DOI: 10.1097/mbc.0000000000000963] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Antiphospholipid (aPL) antibodies can arise transiently at times of viral diseases. The objective of this work was to evaluate the incidence of aPL antibodies in patients hospitalized in conventional unit for coronavirus disease 2019 (COVID-19) infection and confirmed venous thromboembolic events (VTE) associated with aPL antibodies. 41 patients infected with COVID-19 were tested for aPL antibodies. None had reported history of aPL syndrome. Arterial and venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using lower molecular weight heparin with Enoxaparin. Biological parameters were collected and analyzed. Nine patients (22%) developed VTE and seven (17%) were positive for aPL antibodies of which five had isolated positive lupus anticoagulant. The sixth patient was double aPL positive IgM anticardiolipin (147.8 U/ml) and anti-Beta2 Glyco protein 1 (97.3 U/ml) antibodies. The seventh was triple positive, IgM anticardiolipin 85.6 UI/ml, IgM anti-Beta2 Glyco protein 1 63.0 U/ml and positive lupus anticoagulant. Among the seven patients with aPL antibodies 2 (28.60%) had VTE. However, the incidence of VTE in patients negative for aPL antibodies was also significant as 20.6% (seven of 34). aPL antibodies were significantly associated with the transfer to ICUs of, P = 0.018. Not only the incidence of aPL antibodies was quite significant within our cohort, but also we observed 28.6% of VTE in aPL-positive patients. We strongly recommend routine testing for aPL antibodies in COVID-19 patients and systematic screening with duplex ultrasound search of vascular complications.
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Affiliation(s)
| | | | - Ines Harzallah
- Service d'Hémétologie, GHR Mulhouse Sud-Alsace, Hôpital Emile Muller, Mulhouse, France
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Du F, Liu B, Zhang S. COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness. J Thromb Thrombolysis 2021; 51:313-329. [PMID: 32676883 PMCID: PMC7365308 DOI: 10.1007/s11239-020-02224-2] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The novel coronavirus disease (COVID-19) has become a universally prevalent infectious disease. The causative virus of COVID-19 is severe acute respiratory syndrome coronavirus type 2. Recent retrospective clinical studies have established a significant association between the incidence of vascular thrombotic events and the severity of COVID-19. The enhancement in serum levels of markers that reflect a hypercoagulable state has been suggested to indicate a poor prognosis. Therefore, at present, it is crucial to understand the mechanisms that foster the hypercoagulable state in COVID-19. Over-activated inflammatory response, which is manifested as excessive cytokine release in COVID-19 patients, is also associated with COVID-19 severity. This review discusses the immuno-pathological basis of the excessive cytokine release in COVID-19. Besides, this article reviews the role of pro-inflammatory or anti-inflammatory cytokines, whose significant elevations in their serum levels have been consistently detected in multiple different clinical studies, in promoting the hypercoagulable state. Since the expression of angiotensin-converting enzyme 2 (ACE2) is potentially down-regulated in COVID-19, as proposed by a recent bio-informatic analysis, mechanisms through which reduced ACE2 expressions promote vascular thrombosis are summarized. In addition, the reciprocal-enhancing effects of the excessive cytokine release and the downregulated ACE2 expression on their pro-thrombotic activities are further discussed. Here, based on currently available evidence, we review the pathogenic mechanisms of the hypercoagulable state associated with severe cases of COVID-19 to give insights into prevention and treatment of the vascular thrombotic events in COVID-19.
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Affiliation(s)
- Fenghe Du
- Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1st, Dongcheng District, Beijing, 100730, China.,Four-Year Program of Clinical Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Bao Liu
- Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1st, Dongcheng District, Beijing, 100730, China.
| | - Shuyang Zhang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1st, Dongcheng District, Beijing, 100730, China.
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Agrati C, Mazzotta V, Pinnetti C, Biava G, Bibas M. Venous thromboembolism in people living with HIV infection (PWH). Transl Res 2021; 227:89-99. [PMID: 32693031 DOI: 10.1016/j.trsl.2020.07.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 10/23/2022]
Abstract
The risk of venous thromboembolism (VTE) and of recurrent VTE remain elevated in people living with HIV compared to controls still with contemporary antiretroviral therapy (ART). The pathophysiology of VTE in HIV is multi factorial and includes an interplay among traditional risk factors, HIV-specific factors, behavioral factors, exposure to ART and other therapies, coinfections, and co-morbidities.
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Affiliation(s)
- Chiara Agrati
- Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases 'Lazzaro Spallanzani'-IRCCS, Rome, Italy
| | - Valentina Mazzotta
- The Clinical and Research Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani'-IRCCS, Rome, Italy
| | - Carmela Pinnetti
- The Clinical and Research Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani'-IRCCS, Rome, Italy
| | - Gianluigi Biava
- The Clinical and Research Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani'-IRCCS, Rome, Italy
| | - Michele Bibas
- The Clinical and Research Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani'-IRCCS, Rome, Italy.
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Martirosyan A, Aminov R, Manukyan G. Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation. Front Immunol 2019; 10:1609. [PMID: 31354742 PMCID: PMC6635959 DOI: 10.3389/fimmu.2019.01609] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 06/27/2019] [Indexed: 12/19/2022] Open
Abstract
Antiphospholipid antibodies (aPLs) comprise a diverse family of autoantibodies targeted against proteins with the affinity toward negatively charged phospholipids or protein-phospholipid complexes. Their clinical significance, including prothrombotic potential of anti-cardiolipin antibodies (aCLs), anti-β2-glycoprotein I antibodies (aβ2-GPIs), and lupus anti-coagulant (LA), is well-established. However, the ontogeny of these pathogenic aPLs remains less clear. While transient appearance of aPLs could be induced by various environmental factors, in genetically predisposed individuals these factors may eventually lead to the development of the antiphospholipid syndrome (APS). Since the first description of APS, it has been found that a wide variety of microbial and viral agents influence aPLs production and contribute to clinical manifestations of APS. Many theories attempted to explain the pathogenic potential of different environmental factors as well as a phenomenon termed molecular mimicry between β2-GPI molecule and infection-relevant structures. In this review, we summarize and critically assess the pathogenic and non-pathogenic formation of aPLs and its contribution to the development of APS.
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Affiliation(s)
- Anush Martirosyan
- Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology, Yerevan, Armenia.,Russian-Armenian (Slavonic) University, Yerevan, Armenia
| | - Rustam Aminov
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Gayane Manukyan
- Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology, Yerevan, Armenia.,Russian-Armenian (Slavonic) University, Yerevan, Armenia
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12
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Christoforidou A, Galanopoulos N. Diffuse connective tissue disorders in HIV-infected patients. Mediterr J Rheumatol 2018; 29:148-155. [PMID: 32185316 PMCID: PMC7046049 DOI: 10.31138/mjr.29.3.148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 08/29/2018] [Accepted: 09/15/2018] [Indexed: 01/19/2023] Open
Abstract
Background: Human immunodeficiency virus (HIV) infection has been associated with various autoimmune disorders. Aim: To review the spectrum of diffuse connective tissue disorders (dCTD) in HIV-infected patients, in the context of highly active anti-retroviral therapy. Methods: Electronic search of the literature was performed using the terms HIV, AIDS, autoimmune, rheumatic/rheumatological, immune reconstitution inflammatory syndrome, Systemic Lupus Erythematosus, Diffuse Infiltrative Lymphocytosis Syndrome, Sjogren’s syndrome, vasculitis, Behçet’s disease, cryoglobulins, Henoch-Schönlein purpura, and antiphospholipid syndrome. Results: We reviewed the clinical manifestations, natural history and treatment of dCTDs, since the implementation of Highly Active Anti-Retroviral Therapy (HAART), and the emergence of new pathogenic mechanisms, such as the immune reconstitution inflammatory syndrome. Conclusions: Caution in differentiating clinical and laboratory findings of dCTDs from non-specific manifestations of acute and chronic HIV infection is warranted due to the common presentation. Patients with chronic infection and access to HAART have a normal life expectancy and dCTDs, although rare, must be correctly addressed. HAART alone or combined with immunosuppressive therapy result in favourable outcomes.
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Affiliation(s)
- Anna Christoforidou
- Department of Haematology, University General Hospital of Alexandroupolis, Thrace, Greece
| | - Nikolaos Galanopoulos
- Outpatient Department of Rheumatology, University General Hospital of Alexandroupolis, Thrace, Greece
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13
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Kaleidoscope of autoimmune diseases in HIV infection. Rheumatol Int 2016; 36:1481-1491. [DOI: 10.1007/s00296-016-3555-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 08/13/2016] [Indexed: 12/23/2022]
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14
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Peterson LK, Willis R, Harris EN, Branch WD, Tebo AE. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives. Adv Clin Chem 2016; 73:1-28. [PMID: 26975968 DOI: 10.1016/bs.acc.2015.10.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts.
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Affiliation(s)
- Lisa K Peterson
- Department of Pathology, University of Utah, Salt Lake City, Utah, USA
| | - Rohan Willis
- Rheumatology/Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| | | | - Ware D Branch
- Maternal Fetal Medicine, University of Utah and Intermountain Healthcare, Salt Lake City, Utah, USA
| | - Anne E Tebo
- Department of Pathology, University of Utah, Salt Lake City, Utah, USA; ARUP Laboratories, Institute of Clinical and Experimental Pathology, Salt Lake City, Utah, USA.
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Abstract
At the end of 2013, 35 million people worldwide were infected with HIV. The prognosis of HIV has been transformed by combination antiretroviral therapy (cART). Providing compliance is good, the use of cART has normalised the life expectancy of HIV-infected people leading to a growing population of people with chronic infection. Management of HIV patients has therefore needed to adapt in order to not only control viral activity but also manage long-term complications of HIV and cART. Rheumatological manifestations of HIV were first described in 1989. Since then, there have been case reports, case series and epidemiological studies describing different clinical manifestations of HIV in the musculoskeletal system. This review will encompass musculoskeletal pain, fibromyalgia, systemic lupus erythematosus (SLE) and inflammatory arthritis in HIV. We will aim to report on the prevalence of these conditions and the risk factors, explore the impact of the virus on the clinical presentations and discuss implications for diagnosis and management.
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Affiliation(s)
- Christine Fox
- Department of Rheumatology, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
| | - Karen Walker-Bone
- Arthritis Research-UK/MRC Centre for Musculoskeletal Health and Work, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
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Finton KAK, Larimore K, Larman HB, Friend D, Correnti C, Rupert PB, Elledge SJ, Greenberg PD, Strong RK. Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10. PLoS Pathog 2013; 9:e1003639. [PMID: 24086134 PMCID: PMC3784475 DOI: 10.1371/journal.ppat.1003639] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Accepted: 08/04/2013] [Indexed: 01/19/2023] Open
Abstract
The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies.
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Affiliation(s)
- Kathryn A K Finton
- Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
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Singer EJ, Valdes-Sueiras M, Commins DL, Yong W, Carlson M. HIV stroke risk: evidence and implications. Ther Adv Chronic Dis 2013; 4:61-70. [PMID: 23556125 DOI: 10.1177/2040622312471840] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
An estimated 34 million men, women, and children are infected with human immunodeficiency virus type 1 (HIV-1), the virus that causes acquired immunodeficiency syndrome (AIDS). Current technology cannot eradicate HIV-1, and most patients with HIV-1-infection (HIV+) will require lifelong treatment with combined antiretroviral therapy (cART). Stroke was recognized as a complication of HIV-1 infection since the early days of the epidemic. Potential causes of stroke in HIV-1 include opportunistic infections, tumors, atherosclerosis, diabetes, hypertension, autoimmunity, coagulopathies, cardiovascular disease, and direct HIV-1 infection of the arterial wall. Ischemic stroke has emerged as a particularly significant neurological complication of HIV-1 and its treatment due to the aging of the HIV+ population, chronic HIV-1 infection, inflammation, and prolonged exposure to cART. New prevention and treatment strategies tailored to the needs of the HIV+ population are needed to address this issue.
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Affiliation(s)
- Elyse J Singer
- National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine at UCLA, 11645 Wilshire Blvd, Suite 770, Los Angeles, CA 90025, USA
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Swensen S, Schwarzkopf R. Total joint arthroplasty in human immunodeficiency virus positive patients. Orthop Surg 2013; 4:211-5. [PMID: 23109304 DOI: 10.1111/os.12001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Recent advances in the medical management of patients with human immunodeficiency virus (HIV) have led to improvement in their life expectancy. The growing numbers of HIV-positive patients are now living long enough to develop end-stage arthritis, as well as other long-term musculoskeletal complications of HIV infection and treatment. This has resulted in an increased demand for total joint arthroplasty among these individuals. However, the safety and outcomes of such procedures are frequently questioned in published reports. Although increased complication rates have often been reported, most studies have reported on joint arthroplasties in HIV patients with hemophilia. The most widely reported complications in both HIV-negative and positive hemophiliac patients are aseptic loosening and postoperative infection. A possible relationship between the rate of these complications and cluster of differentiation (CD4) lymphocyte count has also been proposed. In addition to hemophilia, other factors frequently comorbid with HIV infection, such as intravenous drug use, can further complicate the clinical outcomes of these individuals following total joint replacement procedures. Physicians treating HIV positive patients must remain aware of the risks and outcomes of total joint surgery in this group when counseling them on treatment options.
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Affiliation(s)
- Stephanie Swensen
- Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, New York, New York, USA
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Abdollahi A, Shoar TS. Hyperhomocysteinemia in HIV-Infected Individuals: Correlation of a Frequent Prothrombotic Factor with CD4+ Cell Count. Oman Med J 2012; 27:224-7. [PMID: 22811772 DOI: 10.5001/omj.2012.50] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Accepted: 04/24/2012] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE This study was aimed at providing an analysis of the correlation between CD4/CD8 counts and some coagulation factors in HIV-Positive Iranian patients. METHODS A case-control study on 58 HIV-infected patients and control group (58 healthy individuals). Patients and controls were matched for sex and age. In this study, several blood parameters were measured in 58 HIV-infected patients and the controls. Laboratory data were then measured including hemoglobin, platelets, homocysteine, serum levels of IgM and IgG antiphospholipid antibodies (aPL), IgM and IgG anticardiolipin antibotdies (aCL), and CD4(+) and CD8(+) cell count. RESULTS The HIV-infected patients, compared to healthy controls, showed a significant decline in platelets, CD4 count and CD8 count (p<0.0001), and an increase of homocysteine (p<0.0001) and IgG aPL levels (p<0.0001). No statistical difference was found between patients with CD4 count ≤200 and CD4 count >200 in the evaluated variables. CONCLUSION The results showed that thrombophilic abnormality in the form of hyperhomocysteinemia is more frequent in HIV-infected patients and should be considered by clinicians in view of an early diagnosis of the hypercoagulability state to prevent thrombotic complications.
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Anderson AM, Chane T, Patel M, Chen S, Xue W, Easley KA. Warfarin therapy in the HIV medical home model: low rates of therapeutic anticoagulation despite adherence and differences in dosing based on specific antiretrovirals. AIDS Patient Care STDS 2012; 26:454-62. [PMID: 22742455 DOI: 10.1089/apc.2012.0068] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
To determine the indications for, rates of therapeutic anticoagulation during, and complications of warfarin therapy in HIV-infected individuals, in whom long-term anticoagulation is frequently indicated. To identify risk factors for nonoptimal anticoagulation and to determine if warfarin dosing is differentially affected by specific antiretroviral agents. Retrospective study of a dedicated anticoagulation program at one of the largest clinics for HIV-infected individuals in the United States. Seventy-three HIV-infected individuals on warfarin were followed for a total of 911 visits. The rate of therapeutic internation normalized ratio (INR) levels was 34.5% when including only visits at which patients were assessed to be adherent with warfarin. In multivariable analysis, injection drug use at baseline was an independent risk factor for subtherapeutic INR (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3-4.7, p=0.01). Additionally, warfarin adherence was protective of both subtherapeutic (OR 0.4, 95% CI 0.2-0.6, p<0.0001) and supratherapeutic (OR 0.5, 95% CI 0.3-0.9, p=0.02) INR status. Efavirenz-based antiretroviral regimens were associated with lower weekly warfarin doses (46 mg) to maintain therapeutic INR compared to lopinavir/ritonavir-based regimens (68 mg; p=0.01) and atazanavir/ritonavir-based regimens (71 mg; p=0.007). Consistently therapeutic warfarin therapy is difficult to achieve in HIV-infected individuals, even with a dedicated anticoagulation program. Adherence to warfarin therapy is important but rates of therapeutic INR levels are nonetheless low. Lower warfarin dosing was required for efavirenz compared to two commonly used protease inhibitor-based regimens. Because of these factors, the emergence of new oral anticoagulants is an important development for HIV-infected individuals who require long term anticoagulation therapy.
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Affiliation(s)
- Albert M. Anderson
- Emory University Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia
- Grady Health System Infectious Diseases Program, Atlanta, Georgia
| | - Tanea Chane
- Grady Health System Infectious Diseases Program, Atlanta, Georgia
| | - Manish Patel
- Grady Health System Infectious Diseases Program, Atlanta, Georgia
| | - Shuo Chen
- Emory University Rollins School of Public Health, Department of Biostatistics and Bioinformatics, Atlanta, Georgia
| | - Wenqiong Xue
- Emory University Rollins School of Public Health, Department of Biostatistics and Bioinformatics, Atlanta, Georgia
| | - Kirk A. Easley
- Emory University Rollins School of Public Health, Department of Biostatistics and Bioinformatics, Atlanta, Georgia
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Franco Moreno AI, de Ancos Aracil CL, Cabello Clotet N, San Martín López JV. [Venous thromboembolism in patients with HIV: A case series]. Enferm Infecc Microbiol Clin 2012; 30:216-7. [PMID: 22365182 DOI: 10.1016/j.eimc.2011.11.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2011] [Revised: 10/19/2011] [Accepted: 11/11/2011] [Indexed: 11/30/2022]
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van Os GMA, Meijers JCM, Agar Ç, Seron MV, Marquart JA, Åkesson P, Urbanus RT, Derksen RHWM, Herwald H, Mörgelin M, D E Groot PG. Induction of anti-β2 -glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes. J Thromb Haemost 2011; 9:2447-56. [PMID: 21985124 DOI: 10.1111/j.1538-7836.2011.04532.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti-β(2) -glycoprotein I (β(2) -GPI) autoantibodies. β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook conformation after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. OBJECTIVE To evaluate the potential of S. pyogenes-derived proteins to induce anti-β(2) -GPI autoantibodies. METHODS AND RESULTS Four S. pyogenes surface proteins (M1 protein, protein H, streptococcal collagen-like protein A [SclA], and streptococcal collagen-like protein B [SclB]) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2) -GPI, thereby exposing a cryptic epitope for APS-related autoantibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody-related epitope in domain I of β(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed anti-protein H antibodies also generated anti-β(2) -GPI antibodies. CONCLUSIONS Our study has demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI, resulting in the formation of antiβ(2) -GPI autoantibodies. This constitutes a novel mechanism for the formation of anti-β(2) -GPI autoantibodies.
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Affiliation(s)
- G M A van Os
- Department of Clinical Chemistry and Hematology, University Medical Center, CX, Utrecht, the Netherlands
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Stricker RB, Johnson L. Antiphospholipid antibodies in patients with persistent Lyme disease symptoms. Lupus 2011; 21:346-7. [PMID: 22040690 DOI: 10.1177/0961203311425531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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HIV-Associated Venous Thromboembolism. Mediterr J Hematol Infect Dis 2011; 3:e2011030. [PMID: 21869916 PMCID: PMC3152452 DOI: 10.4084/mjhid.2011.030] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Accepted: 06/24/2011] [Indexed: 01/31/2023] Open
Abstract
HIV infection has been recognized as a prothrombotic condition and this association has now been proven by a large number of studies with a reported VTE frequency among HIV-infected patients ranging from 0.19% to 7,63 %/year. HIV infection is associated with a two to tenfold increased risk of venous thrombosis in comparison with a general population of the same age. Some risk factors demonstrated a strongest association with VTE such as, low CD4+ cell count especially in the presence of clinical AIDS, protein S deficiency, and protein C deficiency. Whereas other risk factors are still controversial like protease inhibitor therapy, presence of active opportunistic infections and presence of antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. Physicians caring for HIV positive patients should be able to recognize and treat not only the well-known opportunistic infections and malignancies associated with this chronic disease, but also be alert to the less well-known complications such as thromboses. Pulmonary embolism should be included in the differential diagnosis when patients with HIV/AIDS have unexplained dyspnea or hypoxemia. In younger individuals with VTE, especially men, without other identifiable risk factors for VTE, HIV should be considered. Because interactions between warfarin and antiretrovirals is possible, health care providers should also be alert to the potential of dangerously high or low INRs when they are giving anticoagulants to patients with HIV infection who are undergoing antiretroviral therapy.
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Abdollahi A, Morteza A. Serum concentrations of antiphospholipid and anticardiolipin antibodies are higher in HIV-infected women. Rheumatol Int 2011; 32:1927-32. [DOI: 10.1007/s00296-011-1859-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2010] [Accepted: 02/18/2011] [Indexed: 10/18/2022]
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Diaz JS, Octavio JG, Fernandez-Guerrero ML. Antiphospholipid syndrome and acute HIV infection. Emerg Infect Dis 2010; 16:360-1. [PMID: 20113589 PMCID: PMC2958003 DOI: 10.3201/eid1602.090728] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Abstract
Currently, the origin of autoimmune diseases is considered to be multifactorial. Genetic predisposition, immune system malfunction or even backfire, hormonal regulation, and environmental factors, i.e. infections, all play important roles in the pathogenesis of autoimmune diseases such as the antiphospholipid syndrome (APS). New drugs and strategies aimed at preventing infections could further improve the outcome of APS and other autoimmune diseases.
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Morales E, Gutierrez-Solis E, Gutierrez E, Gonzalez R, Martinez MA, Praga M. Malignant hypertension in HIV-associated glomerulonephritis. Nephrol Dial Transplant 2008; 23:3901-7. [DOI: 10.1093/ndt/gfn407] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Atta A, Estevam P, Paraná R, Pereira C, Leite B, Sousa-Atta M. Antiphospholipid antibodies in Brazilian hepatitis C virus carriers. Braz J Med Biol Res 2008; 41:489-92. [DOI: 10.1590/s0100-879x2008005000024] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2007] [Accepted: 05/26/2008] [Indexed: 12/23/2022] Open
Affiliation(s)
| | | | - R. Paraná
- Universidade Federal da Bahia, Brasil
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Walker UA, Tyndall A, Daikeler T. Rheumatic conditions in human immunodeficiency virus infection. Rheumatology (Oxford) 2008; 47:952-9. [PMID: 18413346 DOI: 10.1093/rheumatology/ken132] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Many rheumatic diseases have been observed in HIV-infected persons. We, therefore, conducted a comprehensive literature search in order to review the prevalence, presentation and pathogenesis of rheumatic manifestations in HIV-infected subjects. Articular conditions (arthralgia, arthritis and SpAs) are either caused by the HIV infection itself, triggered by adaptive changes in the immune system, or secondary to microbial infections. Muscular symptoms may result from rhabdomyolysis, myositis or from side-effects of highly active anti-retroviral therapy (HAART). Osseous complications include osteonecrosis, osteoporosis and osteomyelitis. Some conditions such as the diffuse infiltrative lymphocytosis syndrome and sarcoidosis affect multiple organ systems. SLE may be observed but may be difficult to differentiate from HIV infection. Some anti-retroviral agents can precipitate hyperuricaemia and are associated with arthralgia. When indicated, immunosuppressants and even anti-TNF-alpha agents can be used in the carefully monitored HIV patient. Thus, rheumatic diseases and asymptomatic immune phenomena remain prevalent in HIV-infected persons even after the widespread implementation of highly active anti-retroviral therapy.
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Affiliation(s)
- U A Walker
- Department of Rheumatology, Basel University, Basel, Switzerland.
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Host factors and rheumatic features in HIV/AIDS. INDIAN JOURNAL OF RHEUMATOLOGY 2008. [DOI: 10.1016/s0973-3698(10)60071-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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