Several reports of familial aggregation of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have been described although detailed genetic and immunological studies are scarce. Our aims were to investigate 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 GCA and PMR.
HLA-DRB1 typing was carried out using polymerase chain reaction amplification with specific primers. The study of the circulating T cell repertoire was performed by staining with specific monoclonal antibodies and flow cytometry analysis.
Patient 1 developed GCA at the age of 71, four years prior to the diagnosis of PMR in her older brother. The HLA-DRB1 typing of Patient 1 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 brother 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 showed a pronounced decrease of CD4+/CD45RA+ T cells with respect to her brother with PMR. Both patients carried a significant depletion of CD28 in both 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 but the specificities were different.
We describe an association of GCA and PMR between two first degree relatives with significant genetic and immunologic differences. Our results suggest that the pathogenic mechanisms leading to the development of GCA and PMR are probably multifactorial, and both genetic and environmental factors may contribute to the development of these diseases.