HLA-DQ ASSOCIATIONS AND T-CELL RECEPTOR V-GENE USAGE IN PERIPHERAL-BLOOD OF SWEDISH MYASTHENIA-GRAVIS PATIENTS

To characterize better the functional aspects of the HLA class II asso ciations with myasthenia gravis (MG), T-cell receptor (TCR) V alpha'be ta elements were studied in peripheral blood in 29 Swedish MG patients . HLA typing had previously been done using polymerase chain reaction with sequence-specific primers (PCR-SSP) or combined with sequence-spe cific oligonucleotide probes (PCR-SSO). The TCR V gene expression was determined by fluorescence-activated cell sorter (FAGS) analysis using 12 monoclonal antibodies (mAb) that detected 30-40% of CD4(+) and CD8 (+) T cells,No correlation between HLA-DQ genotype and TCR V elements could be found, nor was any restricted V gene usage seen. Fourteen (48 %) of the patients had T cells showing signs of abnormal expansion in peripheral blood. There was an increased expression of TCR V gene elem ents in CD8(+) T cells in patients (13/29) compared with CD4(+) T cell s in patients (5/29) (P < 0.05) and in unthymectomized patients compar ed with controls (14/56) (P < 0.005). TCR V gene expression was also i ncreased in the CD8(+) population in unthymectomized (7/8) compared wi th thymectomized patients (6/21) (P < 0.01). There was an increased ex pression in both CD4(+) and CD8(+) populations in unthymectomized pati ents (7/8, 88%), compared with thymectomized patients (7/21) (P < 0.05 ). We conclude that the abnormal T-cell expansion in peripheral blood could be a reflection of non-specific pathogenic processes in the musc le and thymus.