Numerous studies in various populations have confirmed the role of genetic factors in the pathogenesis of pemphigus vulgaris. The association of human leukocyte antigen (HLA) class II genes with susceptibility to pemphigus are studied extensively. Identifying other contributing genes is also crucial for explaining the mechanisms that can cause pemphigus vulgaris and help develop novel targeted therapeutic modalities. 

There have been fewer studies in the Indian population to find the association of HLA and non-HLA genes with susceptibility and severity of pemphigus vulgaris. Genomic microarray analysis is a systematic, convenient and innovative technique to explore the genome, effectively explaining various genetic diseases. 

A recent case-control study carried out genomic microarray analysis in a small number of pemphigus vulgaris patients to evaluate their genetic basis using a global screening array.

The study recruited 8 patients with an established diagnosis of pemphigus vulgaris (based on clinical, histopathological and direct immunofluorescence findings) along with healthy controls and noted their clinicodemographic details. It performed venesection and withdrew 5 mL of peripheral blood from both cases and controls for genomic microarray analysis.

The mean age of the patients (2 males and 6 females) was 42.6 ± 9.3 years compared to 33.4 ± 9.4 years among controls (4 males and 4 females). The mean disease duration was 12.0 ± 15.1 months. Among the enrolled patients, 2 had severe disease and 6 had mild-to-moderate pemphigus (the severity was calculated based on the Pemphigus Disease Area Index score).

The study found HLA-DQA1, HLA-DPB2, HLA-DMB and HLA-DQB1 genes to be significantly associated with pemphigus. It also explored the single nucleotide polymorphisms associated with severe pemphigus. The study described HLA-DOB to be significantly associated with severe pemphigus.

The observations in the present study reaffirm the significance of these alleles in disease pathogenesis, along with explaining the new single nucleotide polymorphisms – rs12722039 and rs12722042 in HLA-DQA1 and rs6689 in HLA-DQB1 – whose association with pemphigus is first time explained. Yet another novel observation in this study was the association of pseudogenes HLA-DPB2 – rs2395349, rs9277642, rs9277643 and rs9277657 and HLA-DMB – rs194675 with pemphigus. 

The HLA loci associations found in this study are novel and explain the genetic association of pemphigus. 

Source: Handa S, Mahajan R, Kumar S, et al. Novel HLA alleles associated with pemphigus Vulgaris in Indian population detected by DNA microarray analysis. Indian J Dermatol Venereol Leprol. 2021;87(6):867-9.