FRI0008 Evidence for increased activity of interleukin-6 (IL-6) in seropositive rheumatoid arthritis (RA+), and differential tumour necrosis factor (TNF) receptor expression between ra+ and seronegative ra

Background Despite common pathogenetic events in the effector phase, increasing evidence suggests that RA+ is different from RF and anti-CCP-negative RA-. In particular, genetic evidence and somewhat differential responses to therapy distinguish these subgroups. The IL-6 receptor, consisting of the IL-6 receptor α-chain (CD126) and of glycoprotein 130 (CD130), which is also part of other receptors, can be differentially regulated in inflammatory conditions, as can the homotrimeric TNF receptorsI (CD120a) and II (CD120b). Objectives To profile RA+ and RA- patients with regard to IL-6 and TNF receptors Methods Peripheral blood mononuclear cells (PBMC) of RA+, RA- patients, and healthy individuals (HC) were compared. Most (91%) of the RA+ patients were also positive for anti-CCP antibodies. PBMC were immediately prepared from peripheral venous blood. Serum levels of IL-6 and soluble IL-6R (sIL-6R) were measured by ELISA. For determining the percentages of CD126, CD130, CD120a, and CD120b, positive cells, PBMC were stained with phycoerythrin (PE)-labelled specific or control antibodies. Cells were analyzed on a Becton Dickinson FACSCalibur fluorocytometer, gating for lymphocytes. Results Disease activity (median (range) CDAI 15.5 (0.3-54.5) and 13.5 (4.4-33.4)) and disease duration (median 6 (0.04-66) vs. 3 (0.04-10) years) were not significantly different between RA+ and RA- patients, respectively. However, lymphocytes of RA+ and RA- patients differed in their lymphocyte expression of the IL-6 receptor and of CD120b+. The percentage of CD126+ lymphocytes in RA+ (48±13 (mean±SD) %) was decreased in comparison with RA- (61±12%, p=0.006) and HC (60±9%, p