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.