Background Tumor necrosis factor (TNF)-α is a major pathologic cytokine in rheumatoid arthritis (RA) and the current target of RA treatment has been on blocking the TNF-α. iRHOM2 is a regulator of TNF-α convertase that mediate the release of TNF-α from immune cells. Moreover, immune complexes (ICs) are known to induce expression of iRHOM2 via Fc receptors (FcλRIIIa/CD16) in monocytes, regulating the production of TNF-α.
Objectives We hypothesized that the expression of iRHOM2 and Fc receptors are up regulated in seropositive RA patients, that is mediated by immune complex.
Methods The level of TNF-α was measured in the serum of seropositive (+) and seronegative (−) RA patients by ELISA. Messenger RNA expression of iRHOM2 and CD16 was evaluated on peripheral blood mononuclear cells of (+) RA, (−) RA patients, and healthy controls. ICs were extracted from serum of RA patients by adding polyethylene glycol. Isolated ICs were added to THP1-cell cultures to examine the induction of iRHOM2 and CD16.
Results Serum level of TNF-α was similar between (+) RA patients and (−) RA patients (3.23±(5.97) pg/ml vs. 1.99±(1.93) pg/ml). Increased iRHOM2 and CD16 mRNA expression was found on PBMC in (+) RA patients compared to those in (−) RA patients (figure). IC isolated from (+) RA patient could enhance the expression of iRHOM2 as well as CD16 from THP-1 cells.
Conclusions iRHOM2, highly expressed in (+) RA monocytes, might be regulated by immune complex containing anti-cyclic citrullinated peptides antibody, although serum TNF-α level was not different in (+) and (−) RA patient.
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Disclosure of Interest None declared