1
|
Abstract
The human organism is a very complex system. To be in good health, its components must function properly. One of the most important systems of an organism is the immune system. It protects the body from the harmful effects of various external and internal agents. Sometimes, however, the immune system starts attacking its own healthy cells, tissues and organs. Then autoimmune diseases arise. They are widespread in recent decades. There is evidence that often autoimmune responses occur due to viral infections. In this paper, a new mathematical model of a general autoimmune disease is proposed. It describes the interactions between viral particles and host cells. The model is formulated by using integro-differential equations of Boltzmann type. This approach is typical for the nonequilibrium statistical mechanics. A preliminary qualitative and quantitative analysis of the model is presented.
Collapse
|
2
|
Abstract
A new mathematical model of a general autoimmune disease is presented. Basic information about autoimmune diseases is given and illustrated with examples. The model is developed by using ideas from the kinetic theory describing individuals expressing certain functions. The modeled problem is formulated by ordinary and partial equations involving a variable for a functional state. Numerical results are presented and discussed from a medical view point.
Collapse
|
3
|
Amirsardari Z, Rahmani F, Rezaei N. Cognitive impairments in HCV infection: From pathogenesis to neuroimaging. J Clin Exp Neuropsychol 2019; 41:987-1000. [PMID: 31405320 DOI: 10.1080/13803395.2019.1652728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
Collapse
Affiliation(s)
- Zahra Amirsardari
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Farzaneh Rahmani
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran
| |
Collapse
|
4
|
Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
Collapse
Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| |
Collapse
|
5
|
Ferri C, Ramos-Casals M, Zignego AL, Arcaini L, Roccatello D, Antonelli A, Saadoun D, Desbois AC, Sebastiani M, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement. Autoimmun Rev 2016; 15:1145-1160. [PMID: 27640316 DOI: 10.1016/j.autrev.2016.09.006] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 07/19/2016] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic conditions. Given the clinical heterogeneity of HCV-EHDs, HCV-infected individuals are inevitably referred to different specialists according to the presenting/prevalent symptom(s); therefore, the availability of comprehensive diagnostic guidelines is necessary for a patient's whole assessment that is decisive for early diagnosis and correct therapeutic approach of various hepatic and HCV-EHDs, regardless of the specific competencies of different physicians or referral centers. In this respect, a multidisciplinary network of experts, the International Study Group of Extrahepatic Manifestations Related to Hepatitis C Virus Infection (ISG-EHCV), was organized with the intention to formulate diagnostic guidelines for the work-up of possible HCV-EHDs. There was a broad consensus among ISG-EHCV members on the proposed guidelines, which essentially are based on two main levels of patient's assessment. At the referral stage, it is proposed that all patients with HCV infection should be invariably examined by means of first-line diagnostic procedures including virological and hepatic parameter evaluation, as well as the detection of clinical findings that may suggest one or more HCV-EHDs. This preliminary assessment should reveal specific HCV-EHDs, which will be deeper analyzed by means of second-line, targeted investigations. The proposed multidisciplinary expert statement represents the first attempt to draw comprehensive diagnostic guidelines for HCV-infected individuals encompassing the entire spectrum of HCV-related disorders, namely typical hepatic manifestations along with less common, often unpredictable HCV-EHDs. The HCV-EHDs may compromise to a substantial degree the overall disease outcome in a significant number of HCV-infected individuals that renders their timely identification and treatment an imperative. In conclusion, the application of standardized but thorough diagnostic guidelines of HCV-EHDs is advisable at the referral stage as well as during the follow-up period of HCV infected patients. It is envisioned that the proposed strategy will result in improvement of clinical outcomes in such patients.
Collapse
Affiliation(s)
- Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Italy; Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Dario Roccatello
- Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Marco Sebastiani
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Department of Rheumatology & Vasculitis Center, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room 32, 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | | |
Collapse
|
6
|
Abstract
Uncommon or orphan diseases are less frequently addressed in mainstream medical journals and, as a consequence, their understanding and clinical recognition may rely on case series or anecdotal data with limited guidelines and management directions. The study of selected underrepresented autoimmune and allergy conditions is the subject of the present issue of Clinical Reviews in Allergy and Immunology to provide peculiar perspectives on common and rare themes. First, allergy remains a major concern for physicians worldwide despite the limited developments over the past years, particularly for antigens such as mite or Alternaria alternata, and due to the increasing incidence of drug hypersensitivity. Second, the female predominance of autoimmune diseases such as systemic sclerosis is well recognized but enigmatic, and a unifying hypothesis remains elusive. Third, the management of conditions triggered by infectious agents as in Guillain-Barre syndrome or mixed cryoglobulinemia is challenging, and clinical guidelines are needed in the setting of infections and autoimmunity. Fourth, gamma-delta T cells represent major players in innate immunity and are the subject of extensive studies in autoimmune diseases to provide new therapeutic targets for disease prevention or modulation in the near future. Ultimately, we acknowledge the major developments in the broad fields of rheumatology and immunology and expect that microbiota definition, epigenetics studies, and microRNA analysis will provide new exciting avenues toward the understanding and treatment of chronic and acute inflammation.
Collapse
Affiliation(s)
- Carlos Dias
- Department of Internal Medicine, Centro Hospitalar São João, 4200-319, Porto, Portugal,
| | | |
Collapse
|
7
|
Damoiseaux J, Cohen Tervaert JW. Diagnostics and treatment of cryoglobulinaemia: it takes two to tango. Clin Rev Allergy Immunol 2015; 47:299-310. [PMID: 24068540 DOI: 10.1007/s12016-013-8390-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Cryoglobulins are immunoglobulins that reversibly precipitate in the cold. They come in different flavours and, as such, are differentially associated with lymphoproliferative diseases (type I), or systemic autoimmune diseases, and/or infectious diseases (type II/III). The clinical manifestations of cryoglobulinaemia result from either hyper-viscosity or small vessel vasculitis. Hepatitis C virus (HCV) is a well-known factor in the aetiology of cryoglobulinaemia, but substantial geographical differences exist in the association between cryoglobulins and HCV. In the absence of any underlying disease, cryoglobulinaemia is referred to as 'idiopathic' or 'essential'. Detection of cryoglobulins in the laboratory is hampered by several pitfalls, in particular in the pre-analytical stage as well as in the quantification. In addition, our personal experience reveals that the detection of rheumatoid factor, most often present in high concentrations in patients with mixed cryoglobulinaemia, relies on the choice of the test system. Hence, interpretation of the laboratory results in relation to the clinical manifestations requires a partnership between the clinician and the laboratory specialist in order to make a correct diagnosis. Treatment options are primarily directed by identification of underlying diseases, i.e. infections or systemic autoimmune diseases. Idiopathic cryoglobulinaemia is treated with corticosteroids and immunosuppression, or B cell depleting anti-CD20 biologicals. In this overview, the recent literature on current laboratory and clinical practice of cryoglobulinaemia is discussed from a personal perspective.
Collapse
Affiliation(s)
- Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands,
| | | |
Collapse
|
8
|
Renauer P, Coit P, Sawalha AH. Epigenetics and Vasculitis: a Comprehensive Review. Clin Rev Allergy Immunol 2015; 50:357-66. [DOI: 10.1007/s12016-015-8495-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
9
|
Tsuneyama K, Baba H, Kikuchi K, Nishida T, Nomoto K, Hayashi S, Miwa S, Nakajima T, Nakanishi Y, Masuda S, Terada M, Imura J, Selmi C. Autoimmune features in metabolic liver disease: a single-center experience and review of the literature. Clin Rev Allergy Immunol 2014; 45:143-8. [PMID: 23842720 DOI: 10.1007/s12016-013-8383-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of non-alcoholic fatty liver disease associated with the metabolic syndrome. The existence of autoimmune features in NASH has been reported, but its significance remains unclear. We herein report the autoantibody profile of 54 patients with histologically proven NASH and further determined the development of autoimmunity in three different murine NASH models (monosodium glutamate, CDAA (choline-deficient L-amino acid-defined), and TSOD (Tsumura Suzuki, Obese Diabetes)) at 48 weeks of age. Forty-eight percent (26/54) of NASH cases were positive for antinuclear (ANA) or antimitochondrial antibody and manifested histological signs of overlap with autoimmune hepatitis and primary biliary cirrhosis, respectively. These patients were significantly older (60 ± 10 versus 50 ± 16 years), more frequently women (81 % versus 43 %), and with more severe portal inflammatory infiltrate compared with patients without autoimmunity. In one third of mice, regardless of the model, we observed a marked lymphoid infiltrate with non-suppurative cholangitis, and several cases were ANA-positive, but none AMA-positive. Our data suggest that autoimmunity may share some pathogenetic traits with the chronic inflammation of NASH, possibly related to advanced age.
Collapse
Affiliation(s)
- Koichi Tsuneyama
- Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
10
|
Probst C, Radzimski C, Blöcker IM, Teegen B, Bogdanos DP, Stöcker W, Komorowski L. Development of a recombinant cell-based indirect immunofluorescence assay (RC-IFA) for the determination of autoantibodies against "rings and rods"-associated inosine-5'-monophosphate dehydrogenase 2 in viral hepatitis C. Clin Chim Acta 2013; 418:91-6. [PMID: 23333419 DOI: 10.1016/j.cca.2013.01.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2012] [Revised: 01/08/2013] [Accepted: 01/08/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Autoantibodies against so-called "rings and rods" structures, as determined by indirect immunofluorescence assay (IFA) using the human cell line HEp-2, have been described in chronic hepatitis C virus (HCV) infected patients treated with interferon/ribavirin. Recently, cytidine triphosphate synthase (CTPS) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the enzyme inhibited by ribavirin, were proposed as the target antigens. We wanted to confirm the identification and setup a robust system for autoantibody testing in routine laboratories. METHODS CTPS and IMPDH2 were individually expressed in HEK293 cells and the recombinant cells were used in IFA (RC-IFA) to analyze sera from 33 anti-"rings and rods" antibody positive individuals with unknown diagnosis, 50 patients with chronic HCV infection, 100 with autoimmune hepatitis, 50 with primary biliary cirrhosis and 50 healthy blood donors. RESULTS We found that all sera with anti-"rings and rods" reacted with recombinant IMPDH2 but none with CTPS. In western blot or ELISA, anti-IMPDH2 positive sera reacted only weakly, if at all, with Escherichia coli derived recombinant IMPDH2 indicating that the autoantibody reaction probably depends on the 3-dimensional conformation of the antigen. A rabbit hyperimmune serum raised against bacterially expressed IMPDH2 produced the ring/rods pattern in IFA using HEp-2. CONCLUSIONS We conclude, that IMPDH2 is indeed the main target of anti-"rings and rods" while CTPS is an unlikely target. Moreover, the novel RC-IFA test system allows a standardized semi-quantitative determination of anti-IMPDH2 basing on a defined recombinant antigen.
Collapse
Affiliation(s)
- Christian Probst
- Institute of Experimental Immunology, EUROIMMUN AG, Lübeck, Germany
| | | | | | | | | | | | | |
Collapse
|
11
|
Achenza MIS, Meda F, Brunetta E, Selmi C. Serum autoantibodies for the diagnosis and management of autoimmune liver diseases. Expert Rev Gastroenterol Hepatol 2012; 6:717-29. [PMID: 23237257 DOI: 10.1586/egh.12.58] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The spectrum of autoimmune liver diseases (AILD) includes primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. The immunological mechanisms triggering the initiation and perpetuation of AILD remains unknown, while autoantigens are now recognized in most cases, and are generally nontraditional in their widespread distribution. Sensitive and specific methods for the detection of serum autoantibodies in patients affected by AILD represent a challenge for researchers and clinicians who desire to obtain an early and certain diagnosis as well as markers of disease control. To this regard, the use and interpretation of serum autoantibodies in AILD may be seen as paradigmatic for the large gaps in our knowledge based on the lack of true population-based studies. The present review article will critically discuss the available evidence on the use of autoantibody findings in the diagnosis or management of autoimmune liver disease.
Collapse
Affiliation(s)
- Maria I S Achenza
- Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | | | | | | |
Collapse
|
12
|
Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
|
13
|
Himoto T, Masaki T. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012; 2012:871401. [PMID: 22988469 PMCID: PMC3440923 DOI: 10.1155/2012/871401] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Revised: 06/13/2012] [Accepted: 06/13/2012] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
Affiliation(s)
- Takashi Himoto
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan.
| | | |
Collapse
|
14
|
Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401].] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
|
15
|
Hassan M, Selimovic D, El-Khattouti A, Ghozlan H, Haikel Y, Abdelkader O. Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies. World J Exp Med 2012; 2:7-25. [PMID: 24520529 PMCID: PMC3905577 DOI: 10.5493/wjem.v2.i2.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2012] [Revised: 04/16/2012] [Accepted: 04/18/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.
Collapse
Affiliation(s)
- Mohamed Hassan
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Denis Selimovic
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Abdelouahid El-Khattouti
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Hanan Ghozlan
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Youssef Haikel
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| | - Ola Abdelkader
- Mohamed Hassan, Denis Selimovic, Youssef Haikel, National Institute of Health and Medical Research, U 977, Faculty of Medicine, and Dental Faculty, 11 Rue Humann, 67085 Strasbourg Cedex, France
| |
Collapse
|