Sequential removal of human leukocyte antigen B (HLA-B) alleles when relative predispositional effects (RPEs) were looked for demonstrated that B*08 is the allele group with the largest contribution in the overall MG patients followed by B*39 and B*40.
We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes.
The HLA-B*08 allele (12.9% in the controls), previously described associated with early onset adult MG, was most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also increased among prepubertal onset MG (23.5%, P = 0.05).
Since DQB1*03 and DPB1*0201 are not in linkage disequilibrium, both these alleles are supposed to be synergistically involved in disease development in early-onset female MG.
These results indicate that both the DPB1*0201 allele and DR53 play key roles in the disease process of MG in early-onset females, and that the genetic background of Japanese females with early-onset MG is different from that of other patients with MG.
In contrast to findings in other autoimmune diseases, the distribution of the PTPN22 polymorphism in this population provides a susceptibility marker for AChR-MG.
Within the MG patients, there was a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG patients, and the value of odds ratios (OR) decreased as the disease became more severe and the age of onset increased.
We confirmed previously established associations of HLA-DRB1(∗)15 (OR = 2.17) and HLA-DRB1(∗)03 (OR = 1.81) alleles with MS, HLA-DRB1(∗)03 with SLE (OR = 2.49), HLA-DRB1(∗)01 (OR = 1.79) and HLA-DRB1(∗)04 (OR = 2.81) with RA, HLA-DRB1(∗)07 with Ps + PsA (OR = 1.79), HLA-DRB1(∗)01 (OR = 2.28) and HLA-DRB1(∗)08 (OR = 3.01) with SSc, and HLA-DRB1(∗)03 with MG (OR = 2.98).
This study provides novel information about HLA susceptibility alleles in Norwegian juvenile MG where HLA-DRB1*04:04 was associated with prepubertal onset.
Among the subgroups, DQB1*02 was significantly more frequent in EOMG (OR: 1.8), in women with MG (OR: 2.4), and in women with EOMG (OR: 2.8), whereas DQA1*0102 and DQB1*502 (OR: 2.3 for both) were increased and DQA1*0103 (OR: 0.04) was decreased in men with MG. Seropositivity was associated with both DQA1*03 (OR: 12.1) and DQB1*0302 (OR: 14.2) in the patient group.
Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4<sup>+</sup> T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression.
Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG.
The meta-analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK-MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05).
These date suggest that LG type of MG may present a particular subset of childhood-onset MG, which is associated with the specific HLA subtypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303.
Association of the AChRalpha-subunit gene (CHRNA), DQA1*0101, and the DR3 haplotype in myasthenia gravis. Evidence for a three-gene disease model in a subgroup of patients.