Human leukocyte antigen class II (DRB1 and DQB1) alleles frequencies in patients with bullous pemphigoid, Stevens–Johnson syndrome and toxic epidermal necrolysis in Russian population

Abstract

BACKGROUND: Bullous pemphigoid is known to be an autoimmune, life-threatening blistering skin disorder characterized by subepidermal blister formation. In bullous pemphigoid activation of B-cell immunity depends on the interaction between T-cell receptors and classic HLA II molecules. Similar interrelation has been revealed in a vast variety of studies on severe allergic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. It was also suggested that Stevens-Johnson syndrome and toxic epidermal necrolysis might be associated both with HLA I and II classes. AIM: To assess the prevalence of HLA-DRB1 and DQB1 alleles at a low and high-resolution levels in patients with bullous pemphigoid and Stevens-Johnson syndrome / toxic epidermal necrolysis. MATERIALS AND METHODS: 29 Bullous pemphigoid, 14 Stevens-Johnson syndrome / toxic epidermal necrolysis patients and 92 health volunteers were included in the study. HLA-DRB1 and DQB1 alleles were assessed by polymerase chain reaction using specific primers. RESULTS: At a low-resolution level, HLA-DRB1*4 (p 0.02) and DRB1*14 (p 0.0015) alleles were statistically significantly revealed in bullous pemphigoid patients compared to health controls. Additionally, at the high-resolution level the predisposing to bullous pemphigoid HLA-DRB1*04:02 allele was also identified (p 0.01). At the low-resolution level of HLA-DQB1 typing we displayed protective and predisposing to bullous pemphigoid alleles HLA-DQB1*1 (p 0.01) and HLA-DQB1*2 (p 0.039) respectively. At the low-resolution level of HLA-DQB1 typing, the chances to obtain DQB1*03:02 allele were 3.71 times higher compared to healthy volunteers (p 0.01). In patients with Stevens-Johnson syndrome / toxic epidermal necrolysis, HLA-DRB1*4 allele was shown to be predisposing (p 0.03). For all other types of HLA alleles (DRB1 and DQB1) at the high-resolution level no any statistically significant results have been observed in these patients. CONCLUSION: We identified HLA-DRB1*4, DRB1*14, DRB1*04:02 alleles predisposing to the development of bullous pemphigoid, with the HLA-DQB1*1 allele being protective for the development of bullous pemphigoid and HLA-DRB1*4 allele predisposing to the development of severe drug reactions of Stevens-Johnson syndrome / toxic epidermal necrolysis. No any protective alleles in Stevens-Johnson syndrome / toxic epidermal necrolysis patients were detected.