22 results on '"D, Saadoun"'
Search Results
2. Antiphospholipid antibodies and thrombotic events in COVID-19 patients hospitalized in medicine ward.
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Le Joncour A, Frere C, Martin-Toutain I, Gougis P, Ghillani-Dalbin P, Maalouf G, Vieira M, Marcelin AG, Salem JE, Allenbach Y, Saadoun D, Benveniste O, and Cacoub P
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- Aged, Aged, 80 and over, Female, Hospitalization, Humans, Male, Middle Aged, Prospective Studies, Antibodies, Antiphospholipid blood, COVID-19 complications, Thrombosis epidemiology
- Published
- 2021
- Full Text
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3. Systemic lupus erythematosus associated with thymoma: A fifteen-year observational study in France.
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Noël N, Le Roy A, Hot A, Saadoun D, Lazaro E, Lévesque H, Le Gouellec N, Meaux-Ruault N, Nguyen T, Costedoat-Chalumeau N, Amieux B, Fontana A, De Gennes C, Fulpin J, Thomas PA, Bluthgen MV, Besse B, and Lambotte O more...
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- Adult, Aged, Female, France, Humans, Male, Middle Aged, Retrospective Studies, Lupus Erythematosus, Systemic complications, Thymoma complications, Thymus Neoplasms complications
- Abstract
Objective: To describe the clinical, biological and pathological characteristics of patients with the association of SLE and thymic epithelial tumors (TET) in a retrospective multicenter series., Methods: Cases diagnosed in France between 2000 and 2015 were collected after a call for observations from the French network for thymic epithelial tumors (RYTHMIC database) and the French National Society of Internal Medicine (SNFMI)., Results: Fourteen patients were identified, the majority were women (93%). The median age at diagnosis of lupus was 43.5 [range: 30-66] years and 43.5 [range: 26-73] years at diagnosis of thymoma. TET required chemotherapy and/or radiotherapy complementary to surgery in >90% cases. Lupus was diagnosed before, simultaneously, or after diagnosis of thymoma in 6, 3 and 5 cases, respectively. Among the lupus manifestations, joint involvement was predominant (78.6%), followed by autoimmune cytopenia (35.7%), cutaneous affections (28.6%), serositis (28.6%) and renal involvement (21.4%). SLE was associated with one or more AID in 5/14 patients. These characteristics were compared with those from 17 patients identified in the literature. Among them, joint and skin involvement as well as pleural/pericardial effusions occurred in >50%. SLE was controlled by prednisone and hydroxychloroquine in the majority of cases, but 7 out of 31 patients had an immunosuppressant., Conclusion: The association of SLE and TET is rare, and its clinical profile seems to be distinguished by the frequency of cytopenias. The management of these patients is complicated by the need to treat cancer, lupus and/or associated autoimmune diseases., Competing Interests: Declaration of Competing Interest Dr. NOEL reports speaker fees from MSD outside the submitted work. Prof. LAMBOTTE reports grants from Gilead, personal fees and non-financial support from BMS, personal fees from MSD, personal fees from Astra Zeneca, personal fees from Incyte, personal fees from Janssen, non-financial support from LFB, non-financial support from CSL Behring, outside the submitted work. Prof. Besse reports sponsored research at Gustave Roussy Cancer Center outside the submitted work; from Abbvie, Amgen, AstraZeneca, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Eli Lilly, GSK, Ignyta, IPSEN, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunopharmaceutics, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. All other authors: no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.) more...
- Published
- 2020
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4. Corticosteroids and immunosuppressive agents for idiopathic recurrent pericarditis.
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Peiffer-Smadja N, Domont F, Saadoun D, and Cacoub P
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- Adult, Female, Humans, Recurrence, Retrospective Studies, Adrenal Cortex Hormones therapeutic use, Immunosuppressive Agents therapeutic use, Pericarditis drug therapy
- Abstract
Recurrent pericarditis is a frequent and troublesome complication of acute pericarditis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are the mainstay of therapy but few data is available on second-line treatment. We retrospectively analyzed 13 patients, 7 females (54%), median age 40 years, with a median of 4 (IQR 1-6) recurrences per patient despite a well conducted first-line treatment and a median follow-up of 59 months (IQR 38-70). Ten patients received corticosteroids as second-line therapy; 6 out of 10 responded to this therapy while 4 needed the addition of azathioprine. Three other patients received an immunosuppressive agent as second-line therapy (azathioprine, methotrexate, mycophenolate mofetyl). Overall, the mean frequency per month (± SD) of pericarditis recurrences was 0.69 (± 0.40) with aspirin/NSAIDs and colchicine, 0.22 (± 0.34) with corticosteroids alone and 0.01 (± 0.04) with immunosuppressive agents (p < 10
-4 ). Immunosuppressive agents including azathioprine, methotrexate and mycophenolate mofetyl seem efficacious and well tolerated in patients with idiopathic recurrent pericarditis unresponsive to corticosteroids, corticosteroids-dependent or when corticosteroids side effects are judged unacceptable., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...- Published
- 2019
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5. Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients.
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de Boysson H, Daumas A, Vautier M, Parienti JJ, Liozon E, Lambert M, Samson M, Ebbo M, Dumont A, Sultan A, Bonnotte B, Manrique A, Bienvenu B, Saadoun D, and Aouba A
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- Aged, Aortic Diseases pathology, Female, Humans, Male, Middle Aged, Retrospective Studies, Aortic Diseases diagnosis, Giant Cell Arteritis diagnosis
- Abstract
Objectives: Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA., Patients and Methods: A retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model., Results: The patients with LVI were younger (p<0.0001), more likely to be women (p=0.01), and showed fewer cephalic symptoms (p<0.0001) and polymyalgia rheumatica (p=0.001) but more extracranial vascular symptoms (p=0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p=0.0003). Repeated aortic imaging procedures were performed at 19months [range: 5-162months] and 17months [range: 6-168months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p=0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34-7.48], p=0.009)., Conclusions: LVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required., (Copyright © 2018 Elsevier B.V. All rights reserved.) more...
- Published
- 2018
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6. Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis).
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Grumet P, Kodjikian L, de Parisot A, Errera MH, Sedira N, Heron E, Pérard L, Cornut PL, Schneider C, Rivière S, Ollé P, Pugnet G, Cathébras P, Manoli P, Bodaghi B, Saadoun D, Baillif S, Tieulie N, Andre M, Chiambaretta F, Bonin N, Bielefeld P, Bron A, Mouriaux F, Bienvenu B, Vicente S, Bin S, Labetoulle M, Broussolle C, Jamilloux Y, Decullier E, and Sève P more...
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- Adult, Cohort Studies, Female, Humans, Male, Middle Aged, Prospective Studies, Uveitis pathology, Diagnostic Tests, Routine methods, Uveitis diagnosis, Uveitis etiology
- Abstract
Purpose: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance., Methods: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not., Results: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed., Conclusion: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations., (Copyright © 2018 Elsevier B.V. All rights reserved.) more...
- Published
- 2018
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7. Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee.
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Sève P, Cacoub P, Bodaghi B, Trad S, Sellam J, Bellocq D, Bielefeld P, Sène D, Kaplanski G, Monnet D, Brézin A, Weber M, Saadoun D, Chiquet C, and Kodjikian L
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- Humans, Uveitis diagnostic imaging, Uveitis diagnosis
- Abstract
Purpose: Diagnosis of uveitis is difficult. Etiologic investigations should take into account the epidemiology of uveitis and should focus on the most severe forms of the disease and those which can be treated. This study was undertaken to establish recommendations for the diagnosis of uveitis., Methods: Recommendations were developed by a multidisciplinary panel of 14 experts, including internists, ophthalmologists, and rheumatologists, and are based on a review of the literature and the results of the ULISSE study, which was the first prospective study to assess the efficacy of a standardized strategy for the etiologic diagnosis of uveitis. The following groups of patients are not included in these recommendations: children, immunocompromised patients, patients with severe retinal vasculitis, and those with specific eye diseases diagnosed by ophthalmologic examination only., Results: Diagnosis should be guided by the medical history of the patient and physical examination. Serologic screening for syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at this stage, investigations oriented by the anatomic characteristics of uveitis are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma release, chest computed tomography (chronic uveitis), cerebral magnetic resonance imaging and anterior chamber tap with interleukin-10 analysis (intermediate or posterior uveitis in patients >40years-old). Other investigations prescribed in the absence of orientation are usually unhelpful., Conclusions: A strategy is proposed for the etiologic diagnosis of uveitis. The benefit of more invasive investigations remains to be determined., (Copyright © 2017 Elsevier B.V. All rights reserved.) more...
- Published
- 2017
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8. International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus.
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Kleinmann JF, Tubach F, Le Guern V, Mathian A, Richez C, Saadoun D, Sacre K, Sellam J, Seror R, Amoura Z, Andres E, Audia S, Bader-Meunier B, Blaison G, Bonnotte B, Cacoub P, Caillard S, Chiche L, Chosidow O, Costedoat-Chalumeau N, Daien C, Daugas E, Derdèche N, Doria A, Fain O, Fakhouri F, Farge D, Gabay C, Guillo S, Hachulla E, Hajjaj-Hassouni N, Hamidou M, Houssiau FA, Jourde-Chiche N, Koné-Paut I, Ladjouz-Rezig A, Lambotte O, Lipsker D, Mariette X, Martin-Silva N, Martin T, Maurier F, Meckenstock R, Mékinian A, Meyer O, Mohamed S, Morel J, Moulin B, Mulleman D, Papo T, Poindron V, Puéchal X, Punzi L, Quartier P, Sailler L, Smail A, Soubrier M, Sparsa A, Tazi-Mezalek Z, Zakraoui L, Zuily S, Sibilia J, and Gottenberg JE more...
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- Humans, Interdisciplinary Communication, Lupus Erythematosus, Systemic immunology, Biological Products therapeutic use, Lupus Erythematosus, Systemic drug therapy, Practice Guidelines as Topic
- Abstract
Background/purpose: Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE., Methods: The recommendations were developed by a formal consensus method. This method aims to formalize the degree of agreement among experts by identifying, through iterative ratings with feedback, the points on which experts agree, disagree or are undecided. Hence, the recommendations are based on the agreed-upon points. We gathered the opinion of 59 French-speaking SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco, Switzerland and Tunisia. Represented medical specialities were internal medicine (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups contributed to developing these recommendations: a steering group (SG) (n=9), an evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary recommendations were drafted by the SG, then proposed to the EG. Each EG member rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each recommendation. After 2 rating rounds, the SG submitted a new version of the recommendations to the RG. With comments from the RG, the SG finalised the recommendations., Results: A total of 17 final recommendations were formulated by the SG, considering all agreement scores and comments by the EG and RG members and the two methodologists. These recommendations define the subset of patients who require a biologic; the type of biologics to use (belimumab, rituximab, etc.) depending on the organ involvement and associated co-treatments; what information should be given to patients; and how to evaluate treatment efficacy and when to consider discontinuation., Conclusion: Overall, 17 recommendations for the good use of biologics in SLE were formulated by a large panel of SLE experts to provide guidance for clinicians in daily practice. These recommendations will be regularly updated according to the results of new randomized trials and increasing real life experience., (Copyright © 2017 Elsevier B.V. All rights reserved.) more...
- Published
- 2017
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9. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement.
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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, and Cacoub P
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- Humans, Antiviral Agents therapeutic use, Health Planning Guidelines, Hepacivirus metabolism, Hepatitis C complications
- 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., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2017
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10. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement.
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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, and Cacoub P
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- Health Planning Guidelines, Humans, Hepacivirus metabolism, Hepatitis C complications
- 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., (Copyright © 2016. Published by Elsevier B.V.) more...
- Published
- 2016
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11. Shrinking lung syndrome associated with systemic lupus erythematosus: A multicenter collaborative study of 15 new cases and a review of the 155 cases in the literature focusing on treatment response and long-term outcomes.
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Duron L, Cohen-Aubart F, Diot E, Borie R, Abad S, Richez C, Banse C, Vittecoq O, Saadoun D, Haroche J, and Amoura Z
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- Adolescent, Adult, Aged, Female, Humans, Lung Diseases drug therapy, Lung Diseases immunology, Lupus Erythematosus, Systemic drug therapy, Middle Aged, Multicenter Studies as Topic, Retrospective Studies, Syndrome, Treatment Outcome, Young Adult, Immunosuppressive Agents therapeutic use, Lung Diseases etiology, Lupus Erythematosus, Systemic complications
- Abstract
Introduction: Shrinking lung syndrome (SLS) is a rare respiratory manifestation of systemic lupus erythematosus (SLE), characterized by dyspnea, chest pain, elevated hemidiaphragm and a restrictive pattern on pulmonary function tests. Here, we report 15 new observations of SLS during SLE and provide a systematic literature review. We studied the clinical, biological, functional and morphologic characteristics, the treatments used and their efficacy., Methods: The inclusion criteria were all patients with SLE defined by the American College of Rheumatology criteria Hochberg (1997) , associated with a restrictive pattern on pulmonary function tests. The exclusion criteria were all differential diagnoses of restrictive patterns, including obesity and pulmonary fibrosis. The patients were recruited from local databases through chest physicians, rheumatologists and internists. The data for the literature review were extracted from the Medline database using "shrinking lung syndrome" and "lupus" as key words., Results: All 15 new cases were women with a median age at SLS onset of 27years old (range 17-67years). All of them complained of dyspnea and all but one of chest pain. The antibodies were similar to those found in SLE, although the anti-SS-A was positive in 10 of 13 cases. Thoracic imaging showed elevated hemidiaphragm (12/15) and/or basal atelectasia (8/15). All of the patients had an isolated restrictive pattern on PFT, with a median decrease >50% of lung volume. All of the patients were treated, using corticosteroids (11/15), immunosuppressive drugs (8/15), beta-mimetics (2/15), physiotherapy (3/15) and/or colchicine (1/15). Improvement was described in 9 of 12 patients and stability in 3 of 12. We extracted 155 cases of SLE-associated SLS from the Medline database. The clinical, biological and functional parameters were similar to our cases. Clinical improvement was described in 48 of 52 cases (94%) and PFT improvement in 36 of 47 cases. Worsening occurred in 4 cases., Conclusion: SLS is a rare SLE manifestation. Pain and parietal inflammation seem to play important pathogenic roles. Steroids and antalgics are the most commonly used therapies with good responses. There is no proof of efficacy with immunosuppressive drugs for this entity. Rituximab can be discussed after failure of corticosteroids, as well as antalgics, theophylline and beta-mimetics., (Copyright © 2016 Elsevier B.V. All rights reserved.) more...
- Published
- 2016
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12. Biotherapies in large vessel vasculitis.
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Ferfar Y, Mirault T, Desbois AC, Comarmond C, Messas E, Savey L, Domont F, Cacoub P, and Saadoun D
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- Humans, Behcet Syndrome drug therapy, Biological Therapy methods, Giant Cell Arteritis drug therapy, Immunosuppressive Agents therapeutic use, Polychondritis, Relapsing drug therapy, Takayasu Arteritis drug therapy
- Abstract
Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV., (Copyright © 2016 Elsevier B.V. All rights reserved.) more...
- Published
- 2016
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13. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome.
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Noel N, Dutasta F, Costedoat-Chalumeau N, Bienvenu B, Mariette X, Geffray L, Sene D, Chaidi RB, Michot JM, Fain O, Darnige L, Ankri A, Cacoub P, Piette JC, and Saadoun D
- Subjects
- Administration, Oral, Anticoagulants therapeutic use, Factor Xa metabolism, Factor Xa Inhibitors administration & dosage, Factor Xa Inhibitors adverse effects, Hemorrhage chemically induced, Humans, Antiphospholipid Syndrome drug therapy, Factor Xa Inhibitors therapeutic use, Thrombin antagonists & inhibitors
- Abstract
Background: Long-term anticoagulation is recommended in antiphospholipid syndrome with thrombosis in order to prevent recurrences. While the current mainstay relies on vitamin K antagonists, their long-term maintenance may remain challenging., Objectives: To report on the safety and the efficacy of oral direct inhibitors of thrombin and factor Xa (ODIs) in antiphospholipid syndrome (APS)., Methods: We performed a descriptive analysis of patients with APS enrolled in a French multicentre observational cohort between January 2012 and March 2014 and receiving ODIs. The main outcomes were the occurrence of a thrombotic recurrence or bleeding events., Results: Twenty-six patients with APS (primary in 12) received ODIs. Twenty patients had been previously treated with VKA (n=19), or fondaparinux (n=1) for a median duration of 3years. ODIs were introduced as second-line therapy because of INR lability/therapeutic simplification (n=17), recurrent thrombosis (n=1), VKA's associated bleeding event (n=1), and atrial fibrillation (n=1). Six patients received ODIs as first-line therapy. After a median [IQR] follow-up of 19 [8-29] months, one relapse of arterial thrombosis, two bleeding events (hypermenorrhea and rectal bleeding under rivaroxaban) and one recurrent migraine were reported, leading to discontinuation of therapy in these 4 patients., Conclusion: ODIs might be an alternative therapeutic option in APS. Prospective studies are warranted to evaluate their safety in this condition., (Copyright © 2015 Elsevier B.V. All rights reserved.) more...
- Published
- 2015
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14. IFN-α induces IL-10 production and tilt the balance between Th1 and Th17 in Behçet disease.
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Touzot M, Cacoub P, Bodaghi B, Soumelis V, and Saadoun D
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- Humans, Immunologic Memory, Interleukin-10 immunology, Behcet Syndrome immunology, Interferon-alpha immunology, Interleukin-10 biosynthesis, Th1 Cells immunology, Th17 Cells immunology
- Abstract
Background and Aims: Interferon alpha (IFN-α) is an effective treatment for patients with active Behçet disease (BD). Besides its antiviral property, IFN-α is a cytokine with pleiotropic effects that can generate an anti-inflammatory environment or inhibit specific inflammatory T cells such as Th1 and Th17 cells. However, it is not known, in BD patients, whether IFN-α inhibits pro inflammatory T cells, or induces anti-inflammatory properties in T cells., Methods: Total memory CD45RO(+) T cells purified from peripheral blood mononuclear cells (PBMCs) obtained from patients with active BD (N=5), systemic lupus erythematosus (SLE, N=5) or healthy control (HC, N=6) were cultured in vitro with or without IFN-α. Levels of IFN-γ, IL-17, IL-10, IL-6, and TNF-α in the supernatants were analyzed by ELISA, Cytometric Beads Array (CBA) or intracellular cytokine staining. We analyzed the production of IL-10 on the memory subsets Th1 (mTh1), Th2 (mTh2) and Th17 (mTh17)., Results: IFN-α significantly increased IFN-γ level in memory CD4(+) T cells in BD patients and HC, but not SLE patients. IL17 was not inhibited by IFN-α in BD or in SLE patients. However, IFN-α modulated the pro- and anti-inflammatory cytokines secreted by T cells as it increased the IL-10/IL-6 ratio in BD and HC, but not SLE patients. We further demonstrated that IFN-α increased IL-10 secretion in each memory subset mTh1, mTh2 and mTh17., Conclusions: In BD, IFN-α promotes a regulatory Th1 response through IL-10 secretion. This effect may explain the efficacy of IFN-α in inflammatory disease., (Copyright © 2014. Published by Elsevier B.V.) more...
- Published
- 2015
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15. Systemic sclerosis and prevalence of monoclonal immunoglobulin.
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Trad S, Nosbaum A, Musset L, Ghillani-Dalbin P, Launay D, Costedoat-Chalumeau N, Saadoun D, Cabane J, Hachulla E, Hanslik T, and Frances C
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- Antibodies, Monoclonal analysis, Capillaries, Humans, Phenotype, Prevalence, Retrospective Studies, Scleroderma, Systemic epidemiology, Antibodies, Monoclonal immunology, Scleroderma, Systemic immunology
- Abstract
Introduction: The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations., Patients and Methods: Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg., Results: The study included 244 SSc patients (216 women and 28 men, mean age: 55±14 years). Median time since SSc diagnosis was 51 months [0-320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n=1) and multiple myeloma (n=3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p=0.002), had a lower diffusing capacity (p=0.002), a higher prevalence of pulmonary hypertension and cancer (p=0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p=0.03 and p=0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00-1.07, p=0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6-12.4, p=0.004)] were associated with MIg., Conclusion: Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer., (Copyright © 2014 Elsevier B.V. All rights reserved.) more...
- Published
- 2014
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16. Biotherapies in Behçet's disease.
- Author
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Comarmond C, Wechsler B, Bodaghi B, Cacoub P, and Saadoun D
- Subjects
- Behcet Syndrome immunology, Behcet Syndrome pathology, Cytokines immunology, Cytokines metabolism, Cytotoxicity, Immunologic, Humans, Signal Transduction drug effects, T-Lymphocytes, Helper-Inducer immunology, Behcet Syndrome therapy, Biological Therapy
- Abstract
Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD., (Copyright © 2014 Elsevier B.V. All rights reserved.) more...
- Published
- 2014
- Full Text
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17. Serum biomarker signature identifies patients with B-cell non-Hodgkin lymphoma associated with cryoglobulinemia vasculitis in chronic HCV infection.
- Author
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Terrier B, Chaara W, Dufat L, Geri G, Rosenzwajg M, Musset L, Sène D, Saadoun D, Six A, Klatzmann D, and Cacoub P
- Subjects
- Biomarkers blood, Cryoglobulinemia etiology, Cryoglobulinemia pathology, Hepatitis C, Chronic complications, Humans, Lymphoma, B-Cell etiology, Lymphoma, Non-Hodgkin etiology, Vasculitis etiology, Cryoglobulinemia blood, Hepatitis C, Chronic blood, Lymphoma, B-Cell blood, Lymphoma, Non-Hodgkin blood, Vasculitis blood
- Abstract
Background: Hepatitis C virus (HCV) is associated with B-cell disorders, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). We hypothesized that combination of serum biomarkers could be used to identify B-NHL in HCV patients., Methods: We measured in 155 HCV infected patients, with and without MC and/or B-NHL, serum levels of eight markers previously described to be increased in patients with B-NHL, i.e. sCD22, sCD27, sIL-2Rα, sCD137, free-light chains of Ig (ratio κ/λ), heavy chains of Ig (ratio IgMκ/IgMλ), gammaglobulins and C4. We used a multiparametric analysis to determine a signature that identifies patients with overt B-NHL., Results: Serum levels were significantly different between patients without MC, patients with asymptomatic MC, patients with MC vasculitis and those with MC vasculitis and B-NHL for all biomarkers except for sCD137. Using multiparametric analysis, we identified a signature involving sCD27, sIL-2Rα, gammaglobulins and C4 levels associated with the presence of overt B-NHL in HCV-infected patients. This signature had a sensitivity of 100%, a specificity of 90%, and positive and negative predictive values of 97 and 100%, respectively for discriminating patients with overt B-NHL and those without B-NHL., Conclusion: Our data indicate that serum biomarker signature allows identifying HCV-infected patients presenting with overt B-NHL., (Copyright © 2013. Published by Elsevier B.V.) more...
- Published
- 2014
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18. Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies.
- Author
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Saadoun D, Bodaghi B, Bienvenu B, Wechsler B, Sene D, Trad S, Abad S, Cacoub P, Kodjikian L, and Sève P
- Subjects
- Animals, Antibodies, Monoclonal immunology, Eye Diseases immunology, Humans, Immunoglobulins, Intravenous immunology, Inflammation immunology, Antibodies, Monoclonal therapeutic use, Biological Therapy, Eye Diseases therapy, Immunoglobulins, Intravenous therapeutic use, Inflammation therapy, Interferons therapeutic use
- Abstract
Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcet's disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcet's disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis., (Copyright © 2013 Elsevier B.V. All rights reserved.) more...
- Published
- 2013
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19. Small vessel involvement in Takayasu's arteritis.
- Author
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Noel N, Butel N, Le Hoang P, Koskas F, Costedoat-Chalumeau N, Wechsler B, Amoura Z, Bodaghi B, Cacoub P, and Saadoun D
- Subjects
- Adolescent, Adult, Female, Fluorescein Angiography, Humans, Male, Middle Aged, Ophthalmoscopes, Young Adult, Retinal Vessels pathology, Takayasu Arteritis diagnosis
- Abstract
Objectives: To describe the small retinal and systemic vessel involvement in Takayasu's arteritis., Methods: We described 3 patients with Takayasu's arteritis and small retinal vessel occlusion seen in our department between 2004 and 2011. We performed an extensive literature review and provided a global analysis of small retinal vessel involvement in Takayasu arteritis (i.e., total number of patients analyzed=9)., Results: Seven patients had small retinal artery occlusion, and two had venous involvement. Four cases were inaugural of the disease (44.4%). Takayasu's arteritis was extended (Type V) in the majority of patients presenting with small retinal vessel occlusion (5/9, 55.6%), and 8/9 reported cases (88.9%) presented with involvement of the supra-aortic branches. Immunosuppressive regimen allowed an improvement in 5/9 patients and stabilization in 1/9, but the situation worsened in 3/9 patients. The visual outcome was severe, and 3/9 patients (33.3%) experienced irreversible blindness., Conclusion: Occlusion of small retinal vessels is a rare and severe microcirculatory complication in Takayasu's arteritis, as well as necrotizing cutaneous vasculitis or myocarditis. Small retinal vessel involvement can be inaugural of the disease and seriously impact the visual prognosis in TA patients., (Copyright © 2012 Elsevier B.V. All rights reserved.) more...
- Published
- 2013
- Full Text
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20. New insights into the pathogenesis of Behçet's disease.
- Author
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Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, and Saadoun D
- Subjects
- Autoantibodies biosynthesis, Behcet Syndrome pathology, HLA-B51 Antigen physiology, Humans, Inflammation genetics, Inflammation immunology, Inflammation pathology, Receptors, Antigen, T-Cell, gamma-delta physiology, Recurrence, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, T-Lymphocyte Subsets pathology, Behcet Syndrome genetics, Behcet Syndrome immunology, Genetic Predisposition to Disease
- Abstract
Behçet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic [1,2] and immunology [3] of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy., (Copyright © 2011 Elsevier B.V. All rights reserved.) more...
- Published
- 2012
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21. Anti TNF-α in refractory Takayasu's arteritis: cases series and review of the literature.
- Author
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Comarmond C, Plaisier E, Dahan K, Mirault T, Emmerich J, Amoura Z, Cacoub P, and Saadoun D
- Subjects
- Adolescent, Adult, Anti-Inflammatory Agents adverse effects, Antibodies, Monoclonal adverse effects, Child, Etanercept, Female, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Humans, Immunoglobulin G administration & dosage, Immunoglobulin G therapeutic use, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents therapeutic use, Infliximab, Male, Middle Aged, Receptors, Tumor Necrosis Factor administration & dosage, Receptors, Tumor Necrosis Factor therapeutic use, Takayasu Arteritis immunology, Tumor Necrosis Factor-alpha immunology, Young Adult, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Takayasu Arteritis drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Takayasu arteritis (TA) is a rare large vessels vasculitis. Conventional therapy consists of glucocorticoids which may be associated with other immunosuppressive drugs. However, some patients fail to achieve remission with conventional treatment. The use of anti-tumor necrosis factor-α (TNF-α) in patients with difficult to treat TA could be useful. We report here the main characteristics, treatment and outcome of 84 patients (5 personal cases and 79 patients from the literature) with refractory Takayasu arteritis treated with anti TNF-α. The mean age was 28.5years [median 26.0years, range 7-61years], with 74/83 (89%) of female. All patients, except one, were inadequately controlled with other immunosuppressive regimens before anti TNF-α therapy. First line of anti-TNF-α included infliximab (IFX) in 81% (68/84) and etanercept (ETA) in 19% (16/84). Most patients received IFX at 5mg/kg associated to methotrexate or azathioprine. Thirty one out of 84 (37%) patients achieved a complete remission, and 45 (53.5%) were partial responders. There were 8 (9.5%) non responders at all. Twenty seven out of 84 (32%) patients needed to increase the dose of anti TNF-α because of uncontrolled disease and 15 (18%) needed to change of anti TNF-α. Glucocorticoids have been tapered in 41/79 (52%) [from 20mg (13.1-60) to 2.5mg (0-10) daily, at baseline and after anti-TNF, respectively, p<0.0001] and discontinued in 31/77 (40%). After a median follow-up of 10months [range 3-82], 17 (20%) side effects were recorded leading to discontinuation of anti TNF-α in 8 cases. They included mainly infections, and hypersensitivity reactions. In conclusion, anti-TNF-α are an efficient therapy in refractory TA patients although side effects are observed in 20% of cases. Further studies are warranted to assess the long term efficacy and safety of anti-TNF in TA and to better define if they should be prescribed earlier in the course of TA., (Copyright © 2011 Elsevier B.V. All rights reserved.) more...
- Published
- 2012
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22. The pathophysiology of HCV induced B-cell clonal disorders.
- Author
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Landau DA, Saadoun D, Calabrese LH, and Cacoub P
- Subjects
- Cryoglobulinemia virology, Hepatitis C epidemiology, Hepatitis C physiopathology, Humans, Lymphoma, Non-Hodgkin immunology, Lymphoma, Non-Hodgkin virology, B-Lymphocytes immunology, Cryoglobulinemia immunology, Hepacivirus immunology, Hepatitis C immunology
- Abstract
Hepatitis C virus (HCV) has been shown in epidemiologic studies to be associated with immune system disorders. Primarily disorders that stem from B-cell regulatory control disturbance, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL). The causative role of HCV in these disorders is supported by the response to anti-viral treatment. The understanding of the pathophysiological process leading from HCV infection to B-cell clonal expansion has improved significantly. Data supports an antigen-driven indirect stimulation of clonal expansion model, leading from oligoclonal to monoclonal expansion and in some instances to frank malignancy. HCV-E2 antigen has been suggested as a candidate antigen as well as NS3. Binding of the B-cell receptor by viral antigens coupled with direct binding of CD-81 by HCV-E2 has been shown to provide a strong proliferative signal. Additional regulatory elements are also affected in HCV-related B-cell clonal expansion, including the Fas and BLyS signaling mechanisms. Finally, genetic events such as bcl-2 rearrangement may also be involved in clonal expansion. In this review, evidence linking HCV with MC and NHL, as well as known events in the pathophysiological process are described. more...
- Published
- 2007
- Full Text
- View/download PDF
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