A10.10 Examination of IL-6, TNF I and II Receptor Distribution on Peripheral Blood Mononuclear Cells (PBMC) in Seropositive and Seronegative Rheumatoid Arthritis (RA)

Background and Objectives Despite significant clinical overlap, genetic evidence and, in part, response to therapy distinguish seropositive (RA+), i.e. rheumatoid factor (RF) positive RA patients from patients with RF and anti-CCP-negative (RA-) disease. The aim of this study was to profile RA+ and RA- patients with regard to the differential expression of receptors for IL-6 and TNF, cytokines of established importance in RA. Materials and Methods PBMC of RA+ and RA- patients were compared to each other and to healthy individuals (HC). Most (93%) of the RA+ patients were also positive for anti-CCP antibodies. PBMC were immediately prepared from peripheral venous blood. For determining the percentage of IL-6Rα (CD126), gp130 (CD130), TNFR I (CD120a), and TNFR II (CD120b) positive cells, PBMC were stained with PE-labelled or control antibodies. Cells were analysed on a Becton Dickinson FACSCalibur fluorocytometer, gating for lymphocytes. Results Disease duration (median 7 (0.04–66) versus 3.5 (0.04–6) years) and disease activity (CDAI median 15.6 (5.3–54.5) versus 13.5 (4.4–28)) were comparable between RA+ and RA- patients. Lymphocytes of RA+ and RA- patients differed in their lymphocyte expression of CD126+ and CD120b+. The percentage of CD126+ lymphocytes in RA+ was decreased in comparison with RA- (mean ± SD, 49 ± 14 versus RA-58 ± 11, p = 0.05) and HC (59 ± 9%, p = 0.0007). The difference between RA- and HC was not significant. The percentage of CD130+ lymphocytes in RA+ (51 ± 11) was decreased when compared with HC (58 ± 11%, p = 0.007). While the mean values for CD130 were similar between RA+ and RA- (55 ± 14%), the latter values were not significantly different from HC. In contrast to the IL-6 receptor, CD120b+ lymphocytes were increased in RA+ patients (69 ± 12% versus RA- 58 ± 12%, p = 0.04, versus HC 57 ± 11, p = 0.0002). Again, the difference between RA- and HC was not significant. The percentages of CD120a+ lymphocytes were low in all groups. Nevertheless, mean percentages of CD120a+ lymphocytes from RA- (1.5 (0.53–2) % versus HC (median 1 (0.4–4)% p = 0.05) were somewhat higher than those of RA+ (median 1.1 (0.3–3)%, p = 0.9). Conclusions A direct comparison of (IL-6 mediated) downregulation of CD126 and (TNF mediated) upregulation of CD120b suggests that both are clearly more pronounced in RA+ than in RA-0. This was not explained by differences in disease activity.