CD 38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthritis synovial tissues

Summary The purpose of the current study was to find novel rheumatoid arthritis ( RA )‐specific gene expression by simultaneously comparing the expression profiles of the synovial tissues from patients with RA , osteoarthritis ( OA ) and ankylosing spondylitis ( AS ). The I llumina H uman HT ‐12 v4 E xpression B ead C hip was used to investigate the global gene expression profiles in synovial tissues from RA ( n  = 12), OA ( n  = 14) and AS ( n  = 7) patients. By comparing the profiles in synovial tissues from RA , OA and AS , we identified the CD 38, ankyrin repeat domain 38 ( ANKRD 38), E2F transcription factor 2 ( E 2 F 2), craniofacial development protein 1 ( CFDP 1), cluster of differentiation ( CD )7, interferon‐stimulated exonuclease gene 20 kDa ( ISG 20) and interleukin‐2 receptor gamma ( IL )‐2 RG genes as differentially expressed gene expression in RA synovial tissues. The increased expression of CD 38, E 2 F 2 and IL ‐2 RG , as revealed using real‐time polymerase chain reaction ( PCR ) with synovial tissues from RA ( n  = 30), OA ( n  = 26) and AS patients ( n  = 20), was in agreement with the microarray data. Immunohistochemistry revealed significant CD 38 expression and E 2 F 2 in synovial membranes from RA patients ( n  = 5). The CD 38 + cells had high a percentage in the RA patients' blood ( n  = 103) and in the CD 3 + and CD 56 + subsets. The CD 38 + cell percentage was correlated significantly with RF level ( P  = 0·026) in RA patients. The IL ‐1α and IL ‐β levels were depressed significantly in the culture medium of RA synovial fibroblast cells ( n  = 5) following treatment with siRNA s targeting the E 2 F 2 or CD 38 genes. This study suggests that the uniquely increased expression of CD 38 and E 2 F 2 in RA synovial tissues contribute to the immunoactivation of the disease.