HLA-C*17, DQB1*03:01, DQA1*01:03 and DQA1*05:05 Alleles Associated to Bullous Pemphigoid in Brazilian Population

Abstract

BackgroundBullous pemphigoid (BP) is an autoimmune disease with bullous vesicles and an incidence of 0.2 to 1.4 per 100,000 inhabitants. Many studies have been published demonstrating the association of pemphigoid with HLA class II system alleles in different populations, however there are no data on the BP, one of the most heterogeneous in the world.ObjectiveTo typify HLA alleles in Brazilians with Bullous pemphigoid.MethodsThe study group included 17 Brazilian patients with a confirmed diagnosis of BP from a hospital in Sao Paulo city, southeast Brazil. DNA was extracted from peripheral blood using Qiagen kits and HLA A, B, C, DR and DQ typing was performed using polymerase chain reaction. The control group was composed of a database of 297 deceased donors from the city of Sao Paulo. The statistical significance level was adjusted using the Bonferroni correction depending on the phenotypic frequencies evaluated for HLA class I (A, B and C) and class II (DRB1, DQB1 and DQA1).ResultsOur findings show that alleles HLA C*17, DQB1*03:01, DQA1*01:03 and DQA1*05:05 are associated with the onset of the disease in the Brazilian population, with relative risks of 8.31 (2.46 to 28.16), 3.76 (1.81 to 7.79), 3.57 (1.53 to 8.33), and 4.02 (1.87 to 8.64), respectively (p<0.005).ConclusionOur data indicate that Brazilian patients with BP present the same genetic predisposition linked to HLA-DQB1*03:01 previously reported in Caucasian and Iranian individuals and our study introduces three new alleles (C*17, DQA1*01:03 and DQA1*05:05) involved in the pathophysiology of BP.

The pathogenesis of bullous skin diseases

“…Research has also shown that HLA-DQB1*0301 is related to BP and mucous membrane pemphigoid (MMP) [ [82] , [83] , [84] , [85] ]. Dipeptidyl peptidase-4 (DPP-4) inhibitor, a class of drugs commonly used for the treatment of type 2 diabetes, is considered as to be an inducer of BP.…”

Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

“…Interestingly, DQB1 *03:01 has been reported as a susceptibility allele in another dermatological disease: bullous pemphigoid, an organ-specific autoantibody-mediated autoimmune blistering skin disorder in normal patients and in type 2 diabetes mellitus patients receiving dipeptidyl peptidase-IV inhibitors [ 22 , 39 , 40 , 41 , 42 ]. The mechanism of this association is still unclear, but it has been proposed that DQB1 *03:01 could bind bullous pemphigoid 180 (BP180, BP antigen 2, collagen XVII), which may lead to cutaneous disease [ 42 , 43 , 44 ].…”

Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

“…The HLA class II DQB1*03:01 allele is more prevalent in Caucasian patients with BP than in the general population and has also been associated with neurological diseases. 37,38…”