Abstract

Objective: To assess changes in macrophage phenotype and function following rituximab-induced B cell depletion in rheumatoid arthritis (RA) patients.

Patients: Ten patients suffering from RA were treated with rituximab achieving significant B cell depletion four months later. Clinical improvement, rheumatoid factor [RF], anti-cyclic citrullinated peptide [anti-CCP] antibodies, mRNA of BAFF, IL10 and CD86 in human monocyte derived macrophages (HMDM) and TNF-á secretion from cultured HMDM were assessed at baseline and following depletion.

Results: A clinical response of ACR 50 was noted in six patients, and another 2 patients responded with moderate improvement, equivalent to ACR 20-50. RF and anti-CCP antibodies were positive at baseline in seven out of ten patients. Four months following therapy, RF disappeared or declined in 6 patients, correlating with clinical improvement. In contrast, anti-CCP remained unchanged in six. Following rituximab treatment, and in association with clinical improvement, BAFF, IL-10, and CD86 mRNA expression in HMDM, was significantly up- regulated compared with values at baseline. A significant decrease in TNF-á in the supernatant of cultured HMDM was also noted.

Conclusions: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab treated RA patients occurred in association with macrophage function changes.