Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis

With an Italian case series of 81 Italian patients and 130 controls, we ana lysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestra l haplotype, were maximal in females with early onset (EO) MG vs. controls [p < 0.05, relative risk (RR) = 9.9]. These patients showed neither a signi ficantly high frequency of thymic hyperplasia, nor high levels of serum ant i-acethylcholine receptor antibodies. The DRB1*03 allele was absent in pati ents with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p < 0.005; RR = 6.2), more-frequent in females (p < 0.005; RR = 7.8) and most frequent in EOMG female patients (p < 0.005; RR = 15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supra type. and its recombinants showed that the MHC region between C4 and TNF mi ght contain genes that influence susceptibility to MG in females. Polymorph ic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subs et of female MG patients, The combined effect of other intervening genes ca nnot be excluded. (C) 2001 Elsevier Science B.V. All rights reserved.