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Myasthenia gravis (MG) is an autoimmune disease associated with thymic abnormalities (hyperplasia and thymoma). With classical typing method, no clear association was observed between HLA class II and MG disease except in a subgroup of patients with hyperplasia. The aim of our work was to investigate a possible correlation between HLA class II alleles and MG disease using molecular typing which was proved to be much more informative in many diseases. Using polymerase chain reaction and 75 sequence-specific oligonucleotide probes, frequencies of HLA-DRB1, B3, B4, DQA1, DQB1 and DPB1 alleles were identified in 47 Caucasian MG patients and 105 healthy controls. None of the HLA class II alleles identified, was significantly increased in the group of patients compared to controls. However, further analysis of DQA1-DQB1 genotype demonstrated that susceptibility to the disease is associated with two trans DQ alpha beta heterodimers encoded by DQA1*01-DQB1*0201 or DQA1*01-DQB1*0301 combinations (72% in patients vs 29% in controls, RR = 6.2, Pc0.001). DQA1*01 group of alleles (DQA1*0101, 0102 or 0103 allele) encode DQ alpha chains sharing long polymorphic sequence including non-charged glycine and positively charged arginine residues at positions 55 and 64, respectively. DQB1*0301 and DQB1*0201 encode a DQ beta chain bearing a negatively charged glutamic acid at position 45 and 46, respectively. A combination of such DQ alpha and DQ beta chains may form susceptibility peptide-binding groove. In MG patients with thymic hyperplasia an additional association with DQA1*0501 in linkage disequilibrium with DQB1*0201 and DQB1*0301 alleles was observed (RR = 17.2, Pc0.001). Our data indicate that MG, like other autoimmune diseases, is associated with particular HLA-DQ alpha beta heterodimers, independently of clinical parameters. A role for DQA1*0501 allele in the manifestation of thymic hyperplasia disorders is suggested.

The marker association segregation chi-square (MASC) method was applied to a sample of 416 Caucasians affected with insulin-dependent diabetes mellitus (IDDM), for which information on the parental and sibship status was available, as well as HLA typing. We show that the model which best explains all the observations assumes a cis or trans complementation of two tightly linked genes within the HLA region, an additional maternal effect, and other familial factors. The HLA molecule corresponding to the complementation of Arg52(+) and Asp57(-) has been recently proposed as explaining susceptibility to IDDM. However, this hypothesis does not account for the overall observations made on the HLA marker in IDDM patients and their relatives. The MASC method may also be applied to evaluate the risk for relatives of an affected individual (the "index"). For example, the risk for a sib depends not only on the parental status and on the number of HLA haplotypes he shares with the index, but also on which haplotype the index himself inherited from his mother and father.

Relationships with retroviruses have recently been found in different human pathologies as autoimmune diseases which would be associated with the presence and eventually the expression of retroviral sequences. Detection of the presence of HTLV-1 and HIV-1 homologous sequences and their expression was realised on lymphocytes of 14 patients with polyendrocrinopathies (Basedow-Graves' disease and insulin-dependent diabetes) and four relatives of one index case. No antibodies to HTLV-1 and HIV-1 could be detected by Western blot and Elisa tests. HTLV-1 related sequences were revealed by Southern blot (SB) in 5 out of 18 subjects' DNA. Analyses of all DNA were performed by polymerase chain reaction (PCR). Seven DNA, including the 5 previously positive in SB, and two relatives (father and grandfather), negative in SB, contained HTLV-1-gag related sequences, but neither pol nor pX regions. Concerning HIV-1, all 18 DNA examined were negative by both methods. DNA of ten clinically healthy donors were found to be negative with the same tests.