Immunogenetic markers in patients with Graves' disease

Abstract

110 carefully characterized Caucasoid patients with Graves' disease were tested for HLA class I and class II antigens. Compared with Caucasian controls (n = 193), the frequencies of HLA B8, Cw7 and DR3 were significantly increased (pc less than 0.05). In the subgroups with and without exophthalmos, HLA A3 exhibited a negative but insignificant association with the eye involvement, while A19 and Cw2 showed positive, however even weaker correlations with eye disease. HLA DR5 was associated with relapsing thyrotoxicosis, whereas HLA DR7 and B12 were negatively correlated with relapse. These results confirm the positive correlation of HLA B8 and DR3 with Graves' disease and reveal a not yet observed association with Cw7. Reported correlations of antigen frequencies with eye disease and relapsing thyrotoxicosis could not be confirmed. Other previously unknown, however subtle differences in disease subgroups were observed.

HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors

“…In our analysis, the HLA specificities that have 224 been found to be significantly increased in patients with autoimmune thyroid disease were also observed at an increased prevalence in subjects who were mic-TPO positive. Interestingly, also the HLA-DR5 specificity was found with a high prevalence in the autoantibody positives, as has been reported in those with Graves' disease by Schleusner and coworkers and by our group [19,20,24].…”

HLA-DRB3 gene alleles in Caucasian patients with Graves' disease

“…and hypersecretion of thyroxine and tri-iodothyronine [7,8,15,21,22]. The disease is characterized by an undulating course of remission and relapse [71.…”

“…In Caucasians the strongest association is reported for the serologically defined HLA-DR specificities HLA-DR3 and HLA-DR5 [15,21,22]. These HLA specificities belong to the HLADRw52 family characterized by the presence of the HLA-DRB3 gene [3,24].…”

HLA Haplotypes and Susceptibility to Graves’ Disease

“…The association of HLA antigens in various ethnic groups is different: in Cauca sians, Graves' disease has been associated more fre quently with the B8, DR3 and DR5 HLA antigens [4,5]: in Japanese populations, it has been described as an asso ciation with the Bw35 HLA antigen; in the Chinese, with the Bw46 HLA antigen; in northern Nigerians and Black Americans, Graves' disease has been associated more fre quently with the B17 HLA antigen, and in South Africa, the association is more frequent with the B8 HLA antigen [2,6].…”

“…The first immunological studies sug gested that eye involvement in patients with Graves' dis ease was associated with the A 1 and B8 HLA antigens [4], but subsequent studies did not confirm this association [7], Analogous associations were formulated with the DR3 [1] or the Cw3 [8] HLA antigens. It also seems that patients that present B8 on one haplotype and DR7 on another have a higher risk for developing an ophthalmop athy.…”