Analysis of HLA DRB1-DQB1 haplotypes prevalence and their association with severe and refractory pemphigus in Russian population

Introduction. Pemphigus is known to be a life-threatening genetically predisposed autoimmune condition characterized by the formation of IgG antibodies to desmogleins 1 and 3 (Dsg 1, 3) in stratum spinosum and granulosum resulting in blister formation. HLA I and II class antigens express on a vast variety of immune cells including dendritic cells, macrophages, monocytes, Langerhans cells, endothelial cells, and thymic epithelial cells and, therefore play a crucial role in disease’ pathogenesis. The association of pemphigus with HLA alleles has been confirmed through sequencing and genotype analysis across various ethnic groups. In global population the disease development is significantly influenced by specific genetic factors, particularly the HLA alleles DRB1*04:02, DRB1*14:01, DRB1*14:04, and DQB1*05:04. A significant role in the development of pemphigus is attributed to haplotypes, which are combinations of alleles (gene variants). Notably, that the prevalence of DRB 1/DQB 1 haplotypes among patients with pemphigus, as well as their potential association with the disease severity and steroid-resistance in Russian population, has yet to be investigated.

The aim of study. To evaluate the prevalence of HLA-DRB1-HLA-DQB1 haplotypes at low-resolution level in pemphigus patients and their potential association with the disease severity and reluctance to systemic steroid therapy.

Materials and methods. A total of 106 patients with confirmed diagnosis of pemphigus were genotyped for HLA class II genotypes. HLA frequencies were compared with unrelated healthy blood donors (n=92). Disease severity was assessed by PDAI index. The presence of steroid resistance was analyzed using the Murrell consensus from 2008. HLA typing was performed via PCR reaction. The statistical significance of differences between patients and controls was evaluated using Fisher’s exact test.

Results. We found that DRB1*04/DQB1*05 and DRB1*14/DQB1*03 haplotypes predisposed to disease progression in Russian population (p<0,00067; p<0,008643). Moreover, patients who carried these haplotypes showed a tendency towards moderate and severe disease course. However, no statistically significant differences were found for these characteristics. It is also important to highlight that DRB1*11/DQB1*03 haplotype was found exclusively in healthy volunteers indicating its protective role against pemphigus in Russian population.

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