Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases

Chromosomal aberrations were comparatively assessed in nuclei extracted fro m synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases, Peripheral blood lymphocytes (PBL) a nd skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n=4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centrom ere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 IRA patients (19%), with inv olvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 2 1 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomi es of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were dete cted in SFB of OA and spondylarthropathy patients. No aberrations were dete cted in i) PBL or skin FB from the same patients (except for one CA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long -term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joi nts or of patients with joint trauma. In conclusion, qualitatively comparab le chromosomal aberrations were observed in synovial tissue and early-passa ge SFB of patients with RA, OA, and other inflammatory joint diseases. Thus , although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic infl ammatory stress in rheumatic diseases.