Prognostic significance of CD40 expression in malignant lymphoma developing in rheumatoid arthritis

CD40, a member of tumor necrosis factor receptor superfamily, is expressed in synovial fluid B cells in rheumatoid arthritis (RA) and is postulated to contribute to RA progression. In this study, prognostic significance of CD40 expression was analyzed in B cell lymphoproliferative disorders (LPD) developing in RA. CD40 expression was immunohistochemically examined in 35 cases of B-cell LPD developing in RA and in 32 of sporadic B-cell LPD as control. CD40 expression at mRNA level evaluated by quantitative reverse transcription-PCR and at protein level evaluated by immunohistochemistry correlated. Frequency of diffuse large B-cell lymphoma (DLBCL) in RA- and sporadic-LPD was 71.4 and 59.3%, respectively. CD40 positive rate in RA-LPD (62.9%) was significantly higher than that in sporadic LPD (37.5%) (P = 0.015). Interval between onset of RA and LPD development was shorter in CD40 positive cases than in negative cases (median 120 and 204 months, respectively) (P < 0.07). Five-year survival rate in CD40 positive DLBCL cases (75%) was significantly better than that in negative cases (25%) (P < 0.05). RA-LPD is characterized by the higher frequency of CD40 expression compared to sporadic LPD and CD40 positive cases which showed more favorable prognosis than those without CD40 expression.