Demographic and clinical data of our patient population are summarized in . Briefly, a moderate majority of females (58%) over males was observed. This difference was due to a large preponderance of females with early-onset disease, whereas a late onset was more common among males. Twelve (16%) patients had a thymoma. Other categories of MG patients were represented by those with anti-MuSK-Ab (9%), by early-onset patients with (EOAb, 17%) or without (EO, 13%) AChR-Ab, and late-onset patients with (LOAb, 36%) or without (LO, 9%) AChR-Ab.
Demographic and clinical features of the MG patient population.
We did not find any association between MG and HLA class I alleles, neither in the entire survey or in the LOAb subgroup of 27 patients. On the contrary, a strong positive association was found for the HLA class II alleles DQB1*05:02, (Pc
= 0.00768) and DRB1*16 (Pc
= 0.0211) among the 27 patients belonging to the LOAb subgroup ().
HLA class II allele frequency analysis in the LOAb-MG patients subgroup.
In this study, a positive association between the DQB1*05:02 and DRB1*16 alleles with MG was found in a subset of patients, stratified for age at onset higher than 50 years, absence of thymoma, and presence of AChR-Ab. Several associations have been found between HLA antigens or alleles and MG in various ethnic groups, in which the highest risk for MG was consistently conferred to the class II HLA loci. In particular, the DQB1*05:02 has been found to be associated with MG in various populations such as different types of Italian MG patients (except for those with LO) [5
] or male Turkish patients [7
] or with anti-MuSK-positive MG [9
]. Moreover, DQ5, the serologic equivalent of DQB1*05:02, has been shown to be strongly associated with anti-MuSK MG in a Dutch cohort [8
]. Our findings revealed associations between DQB1*05:02 and DRB1*16 with a previously unreported subgroup of patients, representing the most common MG subtype diagnosed in the last two decades [1
Although this hypothesis needs to be confirmed, the lack of association with MG in the whole survey may be due to the presence of patient subgroups not sharing the same HLA alleles, such as the AChR-Ab-negative or the thymomatous patients. Therefore, the apparent discrepancy between our and other results may be ascribed to the variability of different MG subsets and to the changing pattern of incidence of MG [2
]. Interestingly, the occurrence of MG with different antibody specificity (AChR and MuSK) has been described in a mother and daughter sharing the DQ5 antigen [11
We might assume that the DRB1*16-DQB1*05:02 haplotype is at increased risk for MG, since the linkage disequilibrium between these alleles is known; it is, however, possible that only DQB1*05:02 is a susceptibility marker for some forms of MG, considering the higher statistical significance of its association. On the other hand, it must be considered that the HLA genes involved might merely be markers of nearby non-HLA genes responsible for the susceptibility or resistance effects. Further studies in this direction need to be carried out in order to elucidate the full spectrum of immunogenetics of myasthenia gravis.