alexa HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome.
Immunology

Immunology

Immunome Research

Author(s): Vaglio A, Martorana D, Maggiore U, Grasselli C, Zanetti A, , Vaglio A, Martorana D, Maggiore U, Grasselli C, Zanetti A,

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Abstract OBJECTIVE: To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease. METHODS: Low-resolution genotyping of HLA-A, HLA-B, and HLA-DR loci and genotyping of TNFA -238A/G and TNFA -308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls. RESULTS: The frequency of the HLA-DRB1*07 allele was higher in the CSS patients than in controls (27.1\% versus 13.3\%; chi(2) = 12.64, P = 0.0003, corrected P [P(corr)] = 0.0042, odds ratio [OR] 2.42, 95\% confidence interval [95\% CI] 1.47-3.99). The HLA-DRB4 gene, present in subjects carrying either HLA-DRB1*04, HLA-DRB1*07, or HLA-DRB1*09 alleles, was also far more frequent in patients than in controls (38.5\% versus 20.1\%; chi(2) = 16.46, P = 0.000058, P(corr) = 0.000232, OR 2.49, 95\% CI 1.58-3.09). Conversely, the frequency of the HLA-DRB3 gene was lower in patients than in controls (35.4\% versus 50.4\%; chi(2) = 7.62, P = 0.0057, P(corr) = 0.0228, OR 0.54, 95\% CI 0.35-0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)-positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA-DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001). CONCLUSION: These findings indicate that HLA-DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease. This article was published in Arthritis Rheum and referenced in Immunome Research

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