Association of the RAVER2 gene with increased susceptibility for ulcerative colitis.

Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and autoimmune polyglandular syndromes (APS) are autoimmune diseases (ADs) that may share common susceptibility pathways. We examined ribonucleo-protein, polypyrimidine tract-binding protein (PTB)-binding 2 (RAVER2) loci for these diseases in a cohort of 39 CD cases, 67 UC cases, 93 SLE cases, 60 APS cases and 162 healthy control subjects of Tunisian origin. We genotyped 3 SNPs of RAVER2 (rs2780814, rs1333739 and rs2780889) and evaluated it genetic association with each ADs, using X2-test. For each association, odds ratio (OR) and 95% CI were calculated. We show that rs2780814 is significantly associated with UC (P = 0.00016, P(corr) = 0.00048, OR = 3.66 (1.82; 7.34)). We also observed a trend of possible association to SLE (P = 0.023, P(corr) = 0.69, OR = 2.19 (1.1; 4.36)). None of these RAVER2 SNPs were associated with CD and APS susceptibility. These findings establish RAVER2 as a new UC genetic susceptibility factor and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between ADs suggesting different immunopathological roles of RAVER2 in these diseases.

HLA-DRB1/DQB1 susceptibility for autoimmune polyglandular syndrome type II and III in south of Tunisia.

OBJECTIVES: The aim of our study was to investigate the association of HLA-DRB1 and HLA-DQB1 alleles with autoimmune polyglandular syndromes (APS) type II and III in a southern Tunisian population. PATIENTS AND METHODS: Sixty-two unrelated patients with APSII (n=20) and APSIII (n=42) and 146 healthy controls were genotyped for HLA class II alleles (DRB1*, DQB1*) by PCR-SSP technique. RESULTS: An increased frequencies of HLA-DQB1*03:02 (P=0,02; OR=2.98) in APSII patients, HLA-DRB1*03 (P=310(-6); OR=4.28) and HLA-DQB1*02:01 (P=0.04; OR=1.95) in APSIII patients were found compared to healthy controls. Study of the HLA-DRB1*;DQB1* haplotype frequencies showed a higher occurrence of DRB1*04;DQB1*03:02 and DRB1*03;DQB1*02:01 in APSII patients (P=410(-3); OR=3.31 and P=0.03; OR=2.74 respectively) whereas APSIII was only associated with DRB1*03;DQB1*02:01 (P=7.210(-8), OR=4.71). CONCLUSION: Our data suggest that the variation in class II HLA alleles and haplotypes could be a genetic factor involved in the susceptibility of APS syndrome.

Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients.

BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports. OBJECTIVES: To evaluate the presence of a broad spectrum of organ-specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients. PATIENTS AND METHODS: Serum samples were obtained from 105 pemphigus foliaceus (PF) patients, 51 pemphigus vulgaris (PV) patients and 50 controls. Both indirect immunofluorescence assay and ELISA were used to assess the presence of autoantibodies related to connective tissue diseases, autoimmune hepatitis, vasculitis, rheumatoid arthritis, coeliac disease, diabetes and thyroiditis. RESULTS: Significant difference was observed between the three groups for anti-thyroglobulin antibodies in the pemphigus foliaceus group (18% vs. 4%, P=0.03). A significantly higher occurrence of IgM anti-cardiolipin (P=0.03), IgG anti-reticulin (P=0.01) and IgG anti-gliadin antibodies (P=0.008) were observed in the PV group. Cases with more than four autoantibodies were frequently positives for both anti-desmoglein 1 and anti-desmoglein 3. CONCLUSION: Autoantibodies other than anti-desmoglein antibodies are not rare in pemphigus patients. Clinical and serological follow-up of pemphigus patients with positive autoantibodies are needed to clarify their impact in disease evolution.

Enhanced reactivity to malondialdehyde-modified proteins by systemic lupus erythematosus autoantibodies.

OBJECTIVE: Evaluation of the reactivity of autoantibodies of systemic lupus erythematosus (SLE) patients directed against malondialdehyde (MDA)-modified catalase, superoxide dismutase (SOD), and different Hep2 protein fractions (hydrophobic, hydrophilic, and nuclear). METHOD: Thiol groups and MDA-protein adducts were first assessed among 65 SLE patients and 60 healthy controls. Then, the reactivities of SLE immunoglobulin (Ig)G autoantibodies towards MDA-modified and unmodified proteins were compared using a standard enzyme-linked immunosorbent assay (ELISA). RESULTS: An increase in the levels of MDA-modified proteins and a decrease in the concentration of thiol groups among SLE patients (p < 0.05) were observed. IgG circulating autoantibodies in the sera of SLE patients exhibited a significant enhanced reactivity (p < 0.05) against catalase and SOD-modified proteins. The same data were observed in the different protein fractions extracted from cultured cells (p < 0.05). CONCLUSION: These data reinforce the role of oxidative stress and especially lipid peroxidation products in the progression of SLE disease.

[Benzylthiouracil induced ANCA-positive vasculitis: study of three cases and review of the literature]. / Vascularite à anticorps anticytoplasme des polynucléaires neutrophiles induite par le benzylthiouracile: étude de trois observations et revue de la littérature.

INTRODUCTION: Vasculitis with antineutrophilic cytoplasmic antibodies (ANCA) have been reported in patients treated with anti-thyroid drugs, especially propylthiouracil. Benzylthiouracil, which exhibits similar structural likeness with propylthiouracil, has been recently observed to be associated with Anca-positive vasculitis. CASES REPORT: We present a study of three women with Grave's disease aged 21, 37 and 40 years, who were treated with benzylthiouracil. These patients developed vasculitis characterized by constitutional symptoms (two patients), joint pain (two patients), renal involvement (two patients), pulmonary hemorrhage (one patient) and multiple neuropathy (one patient). All patients presented p-ANCA with anti-MPO pattern. Discontinuation of benzylthiouracil and treatment with corticosteroids improved systemic involvement in all patients. CONCLUSION: Much like other anti-thyroid drugs, benzylthiouracil can be associated with ANCA-positive vasculitis. Because of the gravity of this complication, clinical monitoring is recommended in patients taking benzylthiouracil. If vasculitis develops, the anti-thyroid drug should be discontinued and corticosteroid treatment, with immunosuppressors in some cases, is initiated.

Pancreatic autoantibodies in Tunisian children with newly diagnosed type 1 diabetes.

We analyzed 86 children with newly diagnosed type 1 diabetes for antibodies to islet cells (ICA), glutamic acid decarboxylase (GADA), second-islet antigen (IA-2A), and insulin (IAA) in order to evaluate the prevalence of immune-mediated type 1 diabetes, as well as to recognize which autoantibody combination is more frequently associated with the disease. A positive result for one or more diabetes-related antibodies evaluated was found in 78 children (90.7%). With regard to single autoantibody testing, ICA were found to be positive in 49 patients (57%), GADA in 56 (65.1%), IA-2A in 37 (43%), and IAA in 43 (50%) patients. Combining the determination of at least two autoantibodies, GADA and/or IAA were better detectable than other antibody combination, being positive in 70 patients (81.4%). GADA and IA-2A represent also a useful screening combination; being positive in 65 patients (75.6%). Our data indicate that the vast majority of cases of type 1 diabetes in children may be considered as immune-mediated and that multiple autoantibody analysis improves identification of the disease.

[Autoantibodies in systemic lupus erythematosus: spectrum and clinical associations]. / Autoanticorps dans le lupus érythémateux systémique: profil et corrélations cliniques.

We have analysed the clinical features and autoantibody profile of 84 tunisian patients with newly diagnosed systemic lupus erythematosus (SLE). Antinuclear antibodies (ANA) were detected by an immunofluorescence method, anti-dsDNA and anti-cardiolipin (aCL) antibodies by ELISA, antinucleosome and anti-extractible nuclear antigens (or anti-ENA: anti-Sm, anti-RNP, anti-SSA and anti-SSB) by immunodot. The mean age of the patients was 29,9 years and the sex-ratio F/M was 6. The most common initial features were haematological (80%), rheumatological (78%) and cutaneous (75%) disorders. 59% of the patients had glomerular nephropathy. ANA were detected in 97.6%, antinucleosome in 78.6%, anti-dsDNA in 75%, anti-histones in 44%, anti-Sm in 36.9%, anti-RNP in 32.1%, anti-SSA in 54.8% and anti-SSB in 14.3% of patients. IgG and IgM aCL were detected in 45 and 40% of the patients respectively. The significant clinical associations were those of nephropathy and disease activity with anti-dsDNA and antinucleosome antibodies. Our results confirm the clinical polymorphism of SLE, the high frequency of antinucleosome antibodies at time of diagnosis and the predominance of anti-SSA among anti-ENA antibodies.

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients.

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.

[Monoclonal gammapathies in Tunisia: epidemiological, immunochemical and etiological analysis of 288 cases]. / Gammapathies monoclonales en Tunisie: analyse épidémiologique, immunochimique et étiologique d'une série de 288 cas.

From July 1992 to December 2000, 288 cases of monoclonal gammapathy (MG) were collected at the university hospital of Sfax. The middle age of the patients at the time of the diagnosis was 62 years and 7 months with extremes to 18 months and 99 years and median to 64 years. One hundred and eighty-two patients were men and 106 women. Among the 270 observations for which aetiology has been established, 73 were classified MG of undetermined significance (MGUS), 160 myeloma (or plasmocytoma) and 37 other malignant MG (Waldenstrom's macroglobulinemia: 13, lymphoma: 9, alpha heavy chains disease: 6, primary amyloidosis: 5, chronic lymphocytic leukaemia: 4). Rheumatological affections (19.2%), infections and renal failure (10% each), haematological and autoimmune diseases (9.6% each) were pathologies most often associated with MGUS. Agarose gel electrophoresis did not show a monoclonal peak in 16% of the cases. In the 242 patients with a peak on electrophoresis, the peak was in the beta zone in 22% of cases and in the gamma zone in 78% of cases. The IgG isotype represents more than the half of the cases of our set (51.7%). IgG is even more predominant in the MGUS group (65.8%). The IgA isotype counts for 20.8% of the cases in our set and the free light chains (kappa or lambda) for 13.6% of the cases whereas the IgM represents 8.7% only of the 288 cases of our set which involves three cases of IgD myeloma and six cases of biclonal gammapathy.