PT  - JOURNAL ARTICLE
AU  - Stefan Edginton
AU  - Carol Hitchon
AU  - Warren Froese
AU  - Hani El-Gabalawy
TI  - Effects of Rituximab and Infliximab Treatment on Carboxypeptidase B and Its Substrates in RA Synovium
AID  - 10.3899/jrheum.150869
DP  - 2016 Mar 01
TA  - The Journal of Rheumatology
PG  - jrheum.150869
4099  - http://www.jrheum.org/content/early/2016/02/24/jrheum.150869.short
4100  - http://www.jrheum.org/content/early/2016/02/24/jrheum.150869.full
AB  - Objective We evaluated the synovial effects of 2 potent biologic rheumatoid arthritis (RA) therapies, focusing on their effect on the expression level of carboxypeptidase B (CPB) and its substrates. Methods Patients with RA receiving infliximab (IFX; n = 9) or rituximab (RTX; n = 5) had an arthroscopic synovial biopsy at baseline and 16 weeks posttherapy. Expression of CPB, C5a, osteopontin (OPN), CD3, CD20, CD55, and CD68 was assessed by immunohistochemistry and image analysis, and compared with OA synovium. RA disease activity score was assessed at multiple timepoints. Serial serum samples were analyzed for soluble CPB and C5a levels. Results The baseline clinical characteristics of patients receiving IFX and RTX were similar. At the time of the second biopsy, 50% of patients had achieved a European League Against Rheumatism good or moderate response. At baseline, expression of CPB, C5a, and OPN was markedly higher in RA compared with OA synovium and correlated with mononuclear cell infiltration. There was an overall reduction in synovial expression of CPB, C5a, and OPN paralleling a reduction in mononuclear cell infiltration, but these changes were not associated with clinical response. After an early reduction in serum C5a levels, these returned to baseline levels at later timepoints. Conclusion In response to IFX and RTX treatment, RA synovial expression of CPB, C5a, and OPN decrease independently of the clinical response, reflecting the complex proinflammatory and antiinflammatory effects of this pathway.