The increased frequency of DRB1*07:01 in North Indian and Gujarat populations with generalized and localized vitiligo and in several vitiligo populations studied previously suggests that it contributes to autoimmunity and destruction of melanocytes.
Preliminary results showed increased frequencies of DRB1*11- and DRB*16-associated haplotypes that were found to be protective for autoimmune diseases in some populations.
On the basis of these results, the HLA alleles DRB1*0101 and DRB1*0404 and the PTPN22 R620W variant are consistently associated with autoimmunity in the T1DGC Autoantibody Workshop data.
NCA-LEMS was strongly associated with DRB1*0301 (p<0.0001) and DQB1*0201 (p<0.0001), suggesting that NCA-LEMS is an autoimmune disorder associated with the DR3-DQ2 extended haplotype.
We hypothesized that nonislet autoimmunity might be expressed in a similar manner in Korean as well as in Caucasian patients and correlated with the DRB1-DQB1 haplotypes.
A gene dosage effect was observed in the associations of DRB1*13:02 with the protection from systemic autoimmune diseases; thus homozygous individuals are more effectively protected from the systemic autoimmune diseases than heterozygotes.
Our data indicated that there was a generalized genetic factor within or associated with the DRB1*0301/DQA1*0501/DQB1*0201 haplotype, and a more restricted effect with the DRB1*0405/DQA1*0301/DQB1*0401 haplotype which led to thyroid autoimmunity in patients with insulin-dependent diabetes mellitus.
These data suggest that the interaction between VDR and HLA alleles is mediated by VDRE present in the promoter region of HLA-DRB1 0301 allele, which may be detrimental for the manifestation of T1D in the absence of 1,25-(OH)(2)D(3) in early childhood due to poor expression of DRB1 0301 in the thymus resulting in autoimmunity.
In family A, all MS patients and two of five individuals with MS immunopathic trait had HLA DRB1*(15) and in family B, all blood relatives had the rare HLA type DRB1*0103, which is associated with other autoimmune diseases.
In pemphigus vulgaris, a dermatological autoimmune disease, specific human leukocyte antigen (HLA) class II alleles, DR4 (DRB1*0402) and DRw14 (DRB1*1401, in linkage disequilibrium with DQB1*0503), are thought to be susceptibility genes involved in the onset of the disease.
The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general.
Since the DRB1*0301 allele is part of the extended ancestral 8.1 haplotype, it carries with it additional risk factors for autoimmunity, including TNFA*2 and C4A*Q0.
While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS.