Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population

Abstract

The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population.

A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity

“…Therefore, we only included studies where the frequency was given in absolute and relative numbers and data for allele and genotype frequency was analyzed individually. Several studies used a single control group for two different datasets, and to avoid overestimating the number of controls, data of these studies was pooled where possible 74 – 77 (exception: two studies from Serbia 78 , 79 ). All studies included in the meta-analysis reported that the controls and patients derived from the same geographic location or that the controls were ethnically matched to the patients, but most studies did not provide further details on the ethnical matching.…”

A Systematic Review and Meta-Analysis of HLA-Class-II Associations in Patients with IgG4 Autoimmunity

“…Therefore, we only included studies where the frequency was given in absolute and relative numbers and data for allele and genotype frequency were analyzed individually. Several studies used a single control group for two different datasets, and to avoid overestimating the number of controls, data of these studies were pooled where possible [51][52][53][54] (exception: two studies from Serbia 55,56 ). All studies included in the meta-analysis reported that the controls and patients derived from the same geographic location or that the controls were ethnically matched to the controls, but most studies did not provide further details on the ethnical matching.…”

Genetic risk factors for pathogenic IgG4 autoantibodies: a systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmune diseases

“…Therefore, we only included studies where the frequency was given in absolute and relative numbers and data for allele and genotype frequency were analyzed individually. Several studies used a single control group for two different datasets, and to avoid overestimating the number of controls, data of these studies were pooled where possible (52-55) (exception: two studies from Serbia (56,57)). All studies included in the meta-analysis reported that the controls and patients derived from the same geographic location or that the controls were ethnically matched to the controls, but most studies did not provide further details on the ethnical matching.…”