Familial aggregation of polymyalgia rheumatica and giant cell arteritis: Genetic and T cell repertoire analysis

Objective: Several reports of familial aggregation of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have been described although detaile d genetic and immunological studies are scarce. Our aims were to investigat e the influence of HLA-DRB1 alleles and to analyze the phenotype and T cell receptor (TCR) usage of circulating T lymphocytes in a familial case of CC A and PMR. Methods: HLA-DRB1 typing was carried our using polymerase chain reaction am plification with specific primers. The study of the circulating T cell repe rtoire was performed by staining with specific monoclonal antibodies and fl ow cytometry; analysis. Results: patient I developed GCA at the age of 71, four years prior to the diagnosis of PMR in her older brother. The HLA-DRBI typing of Patient I was DRB1 *04 (DRB1 *0401)/DRB1 *12 and in patient 2 was DRB1 *07/DRB1 *12. In our patient population, GCA was associated with an increased frequency, of HLA-DRB1 *04 compared with PMR patients. Regarding T cell phenotype, the br other with active PMR had a higher expression of surface markers indicating activation in both T cell subsets (CD25 and HLA-DR). The sister with GCA s howed a pronounced decrease of CD4+/CD45RA+ T cells with respect to her bro ther with PMR. Both patients carried a significant depletion of CD28 in bot h subsets, specially within the CD8+ T cell compartment. The BV gene usage differed from one patient to the other T cell expansions were identified in both patients bur the specificities were different. Conclusion: We describe an association of GCA and PMR between two first deg ree relatives with significant generic and immunologic differences. Our res ults suggest that the pathogenic mechanisms leading to the development of C CA and PMR are probably multifactorial, and both generic and environmental factors map contribute to the development of these diseases.