MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II AND CLASS-III IN ADDISONS-DISEASE - MHC ALLELES DO NOT PREDICT AUTOANTIBODY SPECIFICITY AND 21-HYDROXYLASE GENE POLYMORPHISM HAS NO INDEPENDENT ROLE IN DISEASE SUSCEPTIBILITY

The major autoantigens in Addison's disease have recently been shown t o be members of the adrenal steroidogenic enzymes, such as 210H. The g enes encoding the 210H enzyme are located in the class III segment of the MHC complex. Therefore, its identification as an autoantigen provi des a novel link between MHC and susceptibility to this autoimmune dis ease. We have determined the MHC class II (DRB1, DQA1, DQB1, DPB1) and class III (TNF, HSP70, C4, 210H) gene polymorphism in patients with A ddison's disease. Also, we tested whether presence of autoantibodies a gainst 210H is associated with specific alleles in MHC. Our results sh ow that patients with Addison's disease in association with APS2 or Ad dison's disease as an isolated form share highly similar MHC class II and class III alleles. A very strong association with HLA DRB10301, D QA10501, DQB1*0201, and DPB1*0101, as well as with the C4A + 210HA ge ne deletion and TNFB1 allele was observed. However, identical gene ma rkers were observed also in controls matched for DRB10301, thus sugge sting that the patient group did not carry MHC gene segments specific for Addison's disease. The presence of autoantibodies against 210H was not found to be directly determined by the MHC alleles; rather it was associated with the clinical form of the disease.