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Joint, bone, spine: revue du rhumatisme 05/2013; · 2.25 Impact Factor
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Chloe Comarmond,
Christian Pagnoux,
Mehdi Khellaf,
Jean-François Cordier,
Mohamed Hamidou,
Jean-François Viallard,
François Maurier,
Stéphane Jouneau,
Boris Bienvenu,
Xavier Puéchal, [......],
Olivier Fain,
Bertrand Godeau,
Raphaèle Seror,
Bertrand Dunogué,
Alfred Mahr, Philippe Guilpain,
Pascal Cohen,
Achille Aouba,
Luc Mouthon,
Loïc Guillevin
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ABSTRACT: OBJECTIVE: Earlier studies on eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome; EGPA), with limited patient numbers and follow-up durations, demonstrated that ANCA+ and ANCA- patients differed clinically at diagnosis but not in their outcomes. Our aims were to describe the main characteristics of a larger patient cohort and their long-term outcomes. METHODS.: Retrospective study on EGPA patients entered into the FVSG database and satisfying the American College of Rheumatology and/or Chapel Hill criteria. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis. RESULTS.: We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] diagnosed ≤1996) and followed for 66.8 ± 62.5 months. At diagnosis, mean age was 50.3 ± 15.7 years and 91.1% had asthma (since 9.3 ± 10.8 years). Main manifestations included peripheral neuropathy (51.4%), ENT signs (48.0%), skin lesions (39.7%), lung infiltrates (38.6%) and cardiomyopathy (16.4%). Among the 348 whose sera were tested at diagnosis for ANCA, the 108 (31.0%) ANCA+ patients had significantly more frequent ENT manifestations, peripheral neuropathy and/or renal involvement, but less frequent cardiac manifestations than ANCA- patients. Vasculitis relapses occurred in 35.2% of ANCA+ versus 22.5% of ANCA- patients (P = 0.01) and 5.6% versus 12.5%, respectively, died (P <0.05). Five-year relapse-free survival was 58.1% [95% CI; 45.6-68.6] for ANCA+ and 67.8% [95% CI; 59.8-74.5] for ANCA- patients (P = 0.35). Multivariable analysis identified cardiomyopathy, older age and diagnosis ≤1996 as independent risk factors for death, and lower eosinophil count at diagnosis as predictive of relapse. CONCLUSION.: EGPA patients differ according to their ANCA status, as do their long-term outcomes. Although EGPA relapses remain frequent, mortality has declined, at least since 1996. © 2012 American College of Rheumatology.
Arthritis & Rheumatism 10/2012; · 7.87 Impact Factor
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ABSTRACT: Objective. Churg-Strauss syndrome (CSS) cardiac involvement is associated with a poor prognosis. Recently cardiac MRI (CMRI) has emerged as a promising technique to detect early CSS cardiac involvement. However, CMRI-detected myocardial delayed enhancement (MDE) could correspond to fibrosis or inflammation. Fluoro-2-deoxyglucose PET (FDG-PET) was previously used in other systemic diseases to distinguish between them. To determine whether the CMRI-MDE detected in CSS patients reflected fibrosis or myocardial inflammation, patients in CSS remission underwent FDG-PET.Methods. Twenty consecutive CSS patients in remission (BVAS = 0) were recruited. Fourteen patients [eight men, six women; mean (s.d.) age 49 (9) years; mean disease duration 3.5 (2.9) years] with CMRI-detected MDE, and six patients [four men, two women; mean (s.d.) age 44 (15) years; mean disease duration 3.5 (5.3) years] with normal CMRI underwent FDG-PET. Segments with MDE on CMRI were analysed on FDG-PET images, with myocardial FDG hypofixation defining fibrosis and hyperfixation corresponding inflammation.Results. Among the 14 patients with MDE on CMRI, FDG-PET showed 10 had hypofixation, 2 had hyperfixation and 2 had normal scans. CSS duration at the time of CMRI was shorter for patients with myocardial inflammation than in those with fibrosis. The six patients with normal CMRI had normal FDG-PET images.Conclusion. For CSS patients in remission, CMRI detected subclinical active myocardial lesions and could be recommended to assess cardiac involvement. However, because CMRI-detected MDE can reflect fibrosis or inflammation, FDG-PET might help to distinguish between the two.
Rheumatology (Oxford, England) 07/2012; · 4.24 Impact Factor
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Cécile Espy,
Willy Morelle,
Niloufar Kavian,
Philippe Grange,
Claire Goulvestre,
Vivian Viallon,
Christiane Chéreau,
Christian Pagnoux,
Jean-Claude Michalski,
Loïc Guillevin,
Bernard Weill,
Frédéric Batteux, Philippe Guilpain
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ABSTRACT: To investigate whether the glycosylation and sialylation levels of anti-proteinase 3 (anti-PR3) antibodies could affect their pathogenicity, and whether these levels could be correlated with the activity of granulomatosis with polyangiitis (Wegener's) (GPA).
Forty-two serum samples positive for anti-PR3 antibodies from 42 patients with active or weakly active/inactive GPA were included. Anti-PR3 antibodies were assayed by enzyme-linked immunosorbent assay, and their levels of glycosylation and sialylation were assessed by enzyme-linked lectin assay. The glycosylation and sialylation levels of IgG purified from the serum of healthy donors and patients with active, remitted, or weakly active disease were assessed by permethylation and mass spectrometry analysis of glycans, following neuraminidase digestion. The neutrophil oxidative burst induced by purified IgG was assayed by spectrofluorimetry.
The mean sialylation ratio of anti-PR3 antibodies was significantly lower in patients with active disease than in patients with weakly active or inactive disease, and this was inversely correlated with the Birmingham Vasculitis Activity Score (BVAS) (P < 0.0001). Similar results were obtained using the BVAS/GPA. The area under the receiver operating characteristic curve for the sialylation ratio of anti-PR3 antibodies, as a test to determine the activity of GPA, was 0.82 (P = 0.0006). The characterization of N-glycans showed a decrease in 2,6-linked sialylated N-glycans and an increase in dHex₁ Hex₃ HexNAc₄ (mass/charge 1,836) agalactosylated structures in purified IgG from patients with active disease compared with controls. The anti-PR3 antibody-induced oxidative burst of neutrophils was inversely correlated with the sialylation levels of anti-PR3 IgG.
The sialylation level of anti-PR3 antibodies contributes to the clinical activity of GPA, by modulating the oxidative burst of neutrophils induced by these autoantibodies.
Arthritis & Rheumatism 03/2011; 63(7):2105-15. · 7.87 Impact Factor
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Acta Dermato-Venereologica 07/2010; 90(4):433-4.
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ABSTRACT: To evaluate the influenza vaccination rate and factors influencing it in patients with SSc.
A total of 177 SSc patients fulfilling the ACR and/or LeRoy and Medsger criteria were evaluated during annual meetings of the French patient association in 2006 (n = 71) and 2007 (n = 70) or during hospitalization in the Internal Medicine Department of Cochin Hospital in 2007 (n = 36). Information on influenza vaccination was collected by a standardized form.
Mean (s.d.) age and disease duration were 58.7 (12.6) and 10.5 (9.5) years, respectively. Overall, 69 (39%) patients received an influenza vaccination during the previous year. Among the 108 patients who were not vaccinated, 78 (72.2%) presented at least one indication for vaccination. The most frequent reasons for non-vaccination were absence of physician recommendation and fear of side effects. Patients who were and were not vaccinated did not differ in anxiety, depression, global disability or quality of life. Vaccination rate was significantly higher (59%) for patients who remembered receiving a letter from the French National Health Insurance Agency encouraging vaccination than among those who did not (26%, P = 0.0001). Multivariate analysis revealed the year of the last vaccination and age as two independent parameters associated with vaccination.
Influenza vaccination coverage is low in SSc patients. Lack of information and fear of adverse effects are the most common reasons for non-vaccination. Efforts are needed to increase the influenza vaccination coverage in this population.
Rheumatology (Oxford, England) 03/2010; 49(3):600-6. · 4.24 Impact Factor
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ABSTRACT: Fanconi syndrome (FS) is a generalized transport defect in the proximal renal tubule leading to renal losses of phosphate, calcium, uric acid, bicarbonates as well as glucose, amino acids and other organic compounds. It is caused by inherited or acquired disorders including low mass or high mass multiple myeloma.
To report the first case series of patients with lymphoma and FS.
Patients with lymphoma and FS were identified in the nephrology department of two teaching hospitals in Paris, France and Ghent, Belgium. FS was defined by the presence of at least three out of the four following criteria: hypophosphataemia, metabolic acidosis, normoglycaemic glucosuria and hypokalaemia. Patients files were reviewed and relevant data were collected.
Eight patients with lymphoma and FS were identified. In six patients, the lymphoma was of the acute T cell leukaemia/lymphoma (ATLL) type, related to human T cell lymphotropic virus 1 (HTLV1) infection. In all patients, FS was severe requiring supplementation. A kidney biopsy performed in a patient with post-transplantation primary renal lymphoma disclosed intense proximal tubule infiltration by lymphomatous cells. In one patient with ATLL, FS features regressed following the successful treatment of lymphoma.
Patients with lymphoma require careful monitoring for features of FS; lymphoma should also be added to the spectrum of disorders associated to FS. Prospective studies are needed to ascertain the implication of HTLV1 in the genesis of FS.
Nephrology Dialysis Transplantation 02/2010; 25(8):2516-20. · 3.40 Impact Factor
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Merav Lidar,
Noga Lipschitz,
Pnina Langevitz,
Ori Barzilai,
Maya Ram,
Bat-Sheba Porat-Katz,
Christian Pagnoux, Philippe Guilpain,
Renato Alberto Sinico,
Antonella Radice,
Nicola Bizzaro,
Jan Damoiseaux,
Jan Willem Cohen Tervaert,
Javier Martin,
Loïc Guillevin,
Stefano Bombardieri,
Yehuda Shoenfeld
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ABSTRACT: In this study we assess the presence of antibodies against infectious agents as well as for a variety of autoantibodies in an attempt to establish associations between various vasculitides and infections in order to shed light on the etiopathogenesis of these diseases and perhaps implicate a potential cure. Sera from patients with Wegener's granulomatosis (WG), polyarteritis nodosa, microscopic polyangiitis, Churg Strauss, and giant cell arteritis were compared to healthy control sera. Serum samples were assessed, using the Bio-Rad BioPlex 2200, for the presence of Toxoplama gondii, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus (HBV), hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. The prevalence of antibodies toward HCV and H. pylori was significantly higher among patients with WG. IgG antibodies toward T. gondii and IgM antibodies toward CMV were significantly more common among WG patients than among controls. WG patients exhibited more antibodies toward EBV viral capsid antigen IgG and EBV early antigen IgG compared to sera from healthy controls. In WG, positive associations were disclosed between CMV IgG antibodies and the presence of gastrointestinal manifestations and renal involvement, and there was a higher Birmingham vasculitis activity score in association with elevated titers of EBV viral capsid antigen IgG antibodies. Otorhinolaryngeal manifestations were more common in those with positive IgG antibodies for EBV early antigen. Our results unveil novel associations between WG and various infectious agents, including HCV, H. pylori, T. gondii, CMV, and EBV. In addition to putative roles in initiation and exacerbation of the vasculitic process, it seems that these infectious agents also modulate the clinical phenotype of the disease.
Annals of the New York Academy of Sciences 09/2009; 1173:649-57. · 3.15 Impact Factor
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Merav Lidar,
Noga Lipschitz,
Pnina Langevitz,
Ori Barzilai,
Maya Ram,
Bat-Sheba Porat-Katz,
Christian Pagnoux, Philippe Guilpain,
Renato Alberto Sinico,
Antonella Radice,
Nicola Bizzaro,
Jan Damoiseaux,
Jan Willem Cohen Tervaert,
Javier Martin,
Loïc Guillevin,
Stefano Bombardieri,
Yehuda Shoenfeld
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ABSTRACT: In this study we assess the presence of antibodies against infectious agents as well as for a variety of autoantibodies in an attempt to establish associations between various vasculitides and infections in order to shed light on the etiopathogenesis of these diseases and perhaps implicate a potential cure. Sera from patients with Wegener's granulomatosis (WG), polyarteritis nodosa, microscopic polyangiitis, Churg Strauss, and giant cell arteritis were compared to healthy control sera. Serum samples were assessed, using the Bio-Rad BioPlex 2200, for the presence of Toxoplama gondii, cytomegalovirus (CMV), Epstein–Barr virus (EBV), Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus (HBV), hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. The prevalence of antibodies toward HCV and H. pylori was significantly higher among patients with WG. IgG antibodies toward T. gondii and IgM antibodies toward CMV were significantly more common among WG patients than among controls. WG patients exhibited more antibodies toward EBV viral capsid antigen IgG and EBV early antigen IgG compared to sera from healthy controls. In WG, positive associations were disclosed between CMV IgG antibodies and the presence of gastrointestinal manifestations and renal involvement, and there was a higher Birmingham vasculitis activity score in association with elevated titers of EBV viral capsid antigen IgG antibodies. Otorhinolaryngeal manifestations were more common in those with positive IgG antibodies for EBV early antigen. Our results unveil novel associations between WG and various infectious agents, including HCV, H. pylori, T. gondii, CMV, and EBV. In addition to putative roles in initiation and exacerbation of the vasculitic process, it seems that these infectious agents also modulate the clinical phenotype of the disease.
Annals of the New York Academy of Sciences 08/2009; 1173(1):649 - 657. · 3.15 Impact Factor
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Amélie Servettaz,
Claire Goulvestre,
Niloufar Kavian,
Carole Nicco, Philippe Guilpain,
Christiane Chéreau,
Vincent Vuiblet,
Loïc Guillevin,
Luc Mouthon,
Bernard Weill,
Frédéric Batteux
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ABSTRACT: Systemic sclerosis (SSc) is a connective tissue disorder of great clinical heterogeneity. Its pathophysiology remains unclear. Our aim was to evaluate the relative roles of reactive oxygen species (ROS) and of the immune system using an original model of SSc. BALB/c and immunodeficient BALB/c SCID mice were injected s.c. with prooxidative agents (hydroxyl radicals, hypochlorous acid, peroxynitrites, superoxide anions), bleomycin, or PBS everyday for 6 wk. Skin and lung fibrosis were assessed by histological and biochemical methods. Autoantibodies were detected by ELISA. The effects of mouse sera on H(2)O(2) production by endothelial cells and on fibroblast proliferation, and serum concentrations in advanced oxidation protein products (AOPP) were compared with sera from patients with limited or diffuse SSc. We observed that s.c. peroxynitrites induced skin fibrosis and serum anti-CENP-B Abs that characterize limited SSc, whereas hypochlorite or hydroxyl radicals induced cutaneous and lung fibrosis and anti-DNA topoisomerase 1 autoantibodies that characterize human diffuse SSc. Sera from hypochlorite- or hydroxyl radical-treated mice and of patients with diffuse SSc contained high levels of AOPP that triggered endothelial production of H(2)O(2) and fibroblast hyperproliferation. Oxidized topoisomerase 1 recapitulated the effects of whole serum AOPP. SCID mice developed an attenuated form of SSc, demonstrating the synergistic role of the immune system with AOPP in disease propagation. We demonstrate a direct role for ROS in SSc and show that the nature of the ROS dictates the form of SSc. Moreover, this demonstration is the first that shows the specific oxidation of an autoantigen directly participates in the pathogenesis of an autoimmune disease.
The Journal of Immunology 06/2009; 182(9):5855-64. · 5.79 Impact Factor
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La Presse Médicale 04/2009; 38(5):844-6. · 0.67 Impact Factor
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B Terrier,
M C Tamby,
L Camoin, P Guilpain,
A Bérezné,
N Tamas,
C Broussard,
F Hotellier,
M Humbert,
G Simonneau,
L Guillevin,
L Mouthon
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ABSTRACT: To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients. Patients and
In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against alpha-enolase from Saccharomyces cerevisiae and recombinant human (rHu) alpha-enolase, respectively, on ELISA.
In the first part, alpha-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae alpha-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu alpha-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae alpha-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu alpha-enolase testing.
In SSc, AFA recognise alpha-enolase and are associated with ILD and antitopoisomerase antibodies.
Annals of the rheumatic diseases 03/2009; 69(2):428-33. · 8.11 Impact Factor
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International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2009; 13(5):e325. · 2.17 Impact Factor
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ABSTRACT: To assess the impact of digital ulcers (DUs) on disability and health-related quality of life (HRQoL) in systemic sclerosis (SSc).
Two hundred and thirteen patients with SSc were evaluated at four annual meetings of a patient society between 2004 and 2007 (n = 177) or during hospital stay (n = 36). HRQoL was assessed by the SF-36, global disability by the health assessment questionnaire (HAQ), hand disability by the Cochin Hand Function Scale (CHFS) and global hand and wrist mobility by the Kapandji index.
Sixty-seven patients (31.4%) had at least one DU at the time of evaluation. Patients with DUs showed significantly more pitting scars (p<0.001) and calcinosis (p<0.0001) than others. Patients with DU had significantly greater HAQ (mean (SD) 1.218 (0.723) vs 0.930 (0.717), p = 0.008), CHFS (mean (SD) 27.38 (20.68) vs 16.73 (18.19), p<0.0001) and aesthetic prejudice (mean (SD) 6.1 (2.2) vs 3.9 (2.5), p<0.0001) scores than others. Hand and wrist mobility were significantly diminished in patients with DU (mean (SD) Kapandji score 75.3 (22.8) vs 81.7 (19.2), p<0.0001). The presence of a DU did not significantly alter the physical component but influenced the mental component (mean (SD) 43.38 (12.53) vs 39.58 (9.54), p = 0.026) of the SF36.
Patients with SSc with DUs have reduced wrist and hand mobility, increased global and hand disabilities and decreased mental component of HRQoL.
Annals of the rheumatic diseases 02/2009; 69(1):214-7. · 8.11 Impact Factor
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La Presse Médicale 12/2008; 38(1):146-8. · 0.67 Impact Factor
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ABSTRACT: To assess patient priorities concerning disability in systemic sclerosis (SSc).
A total of 150 SSc patients (22 men) fulfilling the American College of Rheumatology and/or LeRoy and Medsger criteria for SSc were evaluated by the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), Karnofsky performance status (KPS), Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale, Mouth Handicap in SSc (MHISS) scale, and global perception regarding their health status. Correlations between scores were analyzed using Spearman's coefficient. Logistic regression analysis was used to determine factors associated with patients' global perception of their health.
Of the patients investigated, 81 (54%) had limited cutaneous SSc, 65 (43.3%) diffuse SSc, and 4 (2.7%) limited SSc. The 3 disability domains most often cited were walking (82 patients [54.6%]), housekeeping (67 patients [44.6%]), and sport activities (59 patients [39.3%]). The MACTAR score correlated moderately with KPS (r = 0.58) but only weakly with the HAQ score (r = 0.38). In multivariate analysis, 2 factors were associated with patients' negative global perception of their health status: KPS (odds ratio [OR] 1.07, 95% confidence interval [95% CI] 1.00-1.15) and MHISS score (OR 0.93, 95% CI 0.88-0.99).
For assessing SSc patient priorities concerning disability, the MACTAR has acceptable construct validity. Its weak correlation with the HAQ suggests that it adds useful information on disability.
Arthritis & Rheumatism 08/2008; 59(7):968-73. · 7.87 Impact Factor
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ABSTRACT: Anti-endothelial cell antibodies (AECA) are detectable in a heterogenous group of autoimmune and inflammatory conditions. These antibodies have also been detected in healthy individuals. Nevertheless, most of the literature focuses on AECA in pathological conditions and their targets and functions in healthy individuals remain to be clarified. Recently, proteome-based technologies have been successfully used for the identification of antigens targeted by natural AECA. Thus, it has been shown that IgG AECA can be detected in sera from healthy individuals that recognize a restricted set of proteins among a whole protein extract of umbilical vein endothelial cells. These proteins correspond to ubiquitous proteins belonging to highly conserved protein families and exerting pivotal roles in cell physiology, including cytoskeletal proteins (beta actin, vimentin, alpha tubulin) and glycolytic enzymes (glyceraldehyde-3-phosphate-deshydrogenase and alpha-enolase). As reported for other types of natural autoantibodies, natural AECA could exert anti-inflammatory and anti-thrombotic functions. In addition, they could play a role in the control of EC activation.
Autoimmunity Reviews 07/2008; 7(6):426-30. · 6.62 Impact Factor
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ABSTRACT: Myeloperoxidase (MPO) is a cationic protein present in primary azurophilic granules of neutrophils and monocytes. MPO produces a highly deleterious reactive oxygen species, the hypochlorous acid (HOCl), using hydrogen peroxide (H(2)O(2)) and chloride ions as substrate. Anti-MPO antibodies (Abs) are present in 70% of the cases in patients with microscopic polyangiitis (MPA), a small-sized vessel vasculitis. Anti-MPO Abs from patients with MPA can trigger the release of MPO by neutrophils and monocytes. Anti-MPO Abs can activate MPO to generate an oxidative stress deleterious for the endothelium. Thus, we recently demonstrated that MPA sera with anti-MPO Abs activated MPO in vitro, and generated hypochlorous acid, whereas sera from MPA patients with no anti-MPO Abs or healthy individuals did not. Both hypochlorous acid production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule. Thus, anti-MPO Abs could play a pathogenic role in vivo by triggering an oxidative burst leading to severe endothelial damages.
Autoimmunity Reviews 07/2008; 7(6):421-5. · 6.62 Impact Factor
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Benjamin Terrier,
Mathieu C Tamby,
Luc Camoin, Philippe Guilpain,
Cédric Broussard,
Guillaume Bussone,
Azzedine Yaïci,
Françoise Hotellier,
Gérald Simonneau,
Loïc Guillevin,
Marc Humbert,
Luc Mouthon
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ABSTRACT: Pulmonary arterial hypertension (PAH) may be classified as idiopathic (IPAH) or familial (FPAH) or associated with various conditions and exposures such as dexfenfluramine intake (Dex-PAH) or systemic sclerosis (SSc-PAH). Because fibroblast dysfunction has been identified in SSc and IPAH and antifibroblast antibodies (AFAs) with a pathogenic role have been detected in the serum of SSc patients, we used a proteomic approach combining two-dimensional electrophoresis and immunoblotting to identify the target antigens of AFAs in such patients.
To identify target antigens of antifibroblast antibodies in pulmonary arterial hypertension.
Sera from 24 patients with IPAH, 6 with FPAH, 6 with Dex-PAH, and 12 with SSc-PAH were collected. We pooled sera from sets of three patients with PAH classification and SSc-PAH based on autoantibody profile. Sera from 14 healthy blood donors were also pooled and used as a control.
Serum IgG antibodies in the pools of patients with IPAH (n = 8), FPAH (n = 2), Dex-PAH (n = 2), and SSc-PAH (n = 4) recognized 103 +/- 31, 63 +/- 20, 78 +/- 11, and 81 +/- 12 protein spots, respectively, whereas serum IgG antibodies from healthy control subjects recognized 43 +/- 22 protein spots. Twenty-one protein spots were specifically recognized by the serum IgG antibodies from patients with PAH. We identified 16 of the protein spots as vimentin, calumenin, tropomyosin 1, heat shock proteins 27 and 70, glucose-6-phosphate-dehydrogenase, phosphatidylinositol 3-kinase, DAP kinase, and others. These proteins are involved in regulation of cytoskeletal function, cell contraction, oxidative stress, cell energy metabolism, and other key cellular pathways.
AFAs detected in patients with PAH recognize cellular targets playing key roles in cell biology and maintenance of homeostasis.
American Journal of Respiratory and Critical Care Medicine 06/2008; 177(10):1128-34. · 11.08 Impact Factor
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ABSTRACT: Churg-Strauss syndrome is a systemic and pulmonary vasculitis, defined by its association with severe asthma and with hypereosinophilia of the blood and tissues. The systemic vasculitis is a small-vessel vasculitis frequently associated with purpura, mononeuritis multiplex, and, more rarely, with rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage. Its prevalence of 7 to 13 per million population makes it one of the rarest of the systemic vasculitides. Anti-MPO (antimyeloperoxydase) pANCA (ANCA with a perinuclear fluorescence pattern) are present in 35-40% of cases and appear to determine a subgroup of patients with a higher frequency of renal damage, alveolar hemorrhage, and central nervous system involvement. The diagnosis of Churg-Strauss syndrome is made on the basis of clinical features. In patients with late onset asthma the presence of constitutional symptoms, eosinophilia (> 1000/mm3), the appearance of a systemic illness characterized by monoreutis multiplex, purpura, cardiomyopathy or pulmonary infiltrates should lead to consider the diagnosis of Churg-Strauss syndrome. Cardiac involvement is an important cause of morbidity and the leading cause of specific mortality in Churg-Strauss syndrome. Treatment is based on corticosteroid therapy and immunosuppressive drugs (cyclophosphamide and azathioprine) and is determined according to validated prognostic criteria (Five Factors Score). Complete remission occurs in almost 90% of cases, and the 10-year survival rate has reached 79.4%. Relapses are frequent (25% of cases) and even after recovery from vasculitis, most patients (90%) still have asthma requiring corticosteroid treatment.
La Revue du praticien 06/2008; 58(11):1165-74.
