Patients that carry both the PV-associated human leukocyte antigen (HLA) alleles DRB1*0402 and DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R.
We noticed an increased frequency of HLA-DRB1*04 and DRB1*14 alleles in patients with PV compared with healthy control subjects (67.0% vs. 26.3%; odds ratio [OR] = 5.7, corrected P < 0.0001 for DRB1*04; 54.9% vs. 11.0%; OR = 9.5, corrected P < 0.0001 for DRB1*14).
Dsg3-specific T-cell responses were detected in PV patients but also in healthy individuals who were either carriers of the PV-associated DRB1*0402 allele or alleles that share similar or identical peptide binding motifs to DRB1*0402.
Genetic factors are involved in the occurrence of PV; HLA-DRB1*04 and -DRB1*1401 alleles and the related haplotypes are suggestive to be two major PV susceptibility factors in our population study.
The association between pemphigus vulgaris and eosinophilic esophagitis in this case, although previously unreported, is explicable on the basis of dysregulation of desmoglein 1 (DSG1).
These data indicate that both pemphigus foliaceus and pemphigus vulgaris sera react with conformationally sensitive epitopes in the amino-terminal region of Dsg1.
Autoantibodies to the desmosomal proteins desmoglein 1 and 3 cause pemphigus foliaceus and pemphigus vulgaris, which are characterised by keratinocyte dissociation (acantholysis) and intraepidermal blister formation.
Our findings suggest that HLA DRB1*04 and DRB1*14 alleles, and HLA DRB1*04/DQB1*03 and HLA DRB1*14/DQB1*05 haplotypes are genetic markers for general susceptibility to PV in the Turkish population.
Since 86% (19 of 22) of DRw6+ patients contain the DQB1.3 allele (vs. 3% of controls), whereas 64% (14 of 22) contain the DRB1 allele 6B (vs. 6% of the controls), we conclude that most of the DRw6 susceptibility to PV can be accounted for by the DQ beta chain.
Subjects were typed for HLA class II DRB1 and DQB1 alleles, and categorized as HLA-matched if homozygous or heterozygous for either one of the known PV-susceptibility alleles, DRB1*0402 and DQB1*0503.
Our results support the hypothesis that the DRB1*0402 without DQB1*0302 is the most relevant HLA-DRB1 allele responsible for the pathogenesis of pemphigus in Venezuelan patients with PV and discard the DQB1*0302 influence observed in other populations.
The strength of the allele associations to PV is in agreement with the view that the main PV susceptibility genes are the DRB1*0402 and DQB1*0503 alleles.
The DRB1*04:02 and DQB1*03:02 alleles were associated with severe PV (P = 0.001); DRB1*04:02 was associated with the mucocutaneous type (P = 0.024), and DQB1*03:02 was found more frequently in female than in male patients (P = 0.016).
Thus our findings, together with previous HLA studies on pemphigus vulgaris patients of different ethnic groups, suggest that HLA-DRB1*04 and DRB1*14 alleles are commonly associated with pemphigus vulgaris across racial barriers.
Taking together these data, we can conclude that, in the Spanish population, PV is preferentially and strongly associated with HLA-DRB1*0402, whereas DRB1*13 seems to confer a protective effect in our population.
All DRB1*04 and DRB1*14 alleles carried by PV patients with different ethnic backgrounds reported to date, including DRB1*0402, which confers strong susceptibility to PV among Jewish populations, have amino acid residues Phe26, Leu67 or Ile67, and Val86, as well as hydrophilic amino acid residues at positions 70 and 71 of the DRB1 beta chain.