Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Clinically Defined Subset of dcSSc Is Associated with Elevated Serum IL-6 Level
Ong, Voon, Nihtyanova, Svetlana, Black, Carol M., Denton, Christopher P.
IL-6 is a pleiotropic cytokine and it has been implicated in SSc pathogenesis. We analysed the relationship between serum IL-6 levels and the inflammatory response and modified Rodnan skin score (mRSS) in SSc. Based upon the known stimulatory effect of IL-6 on thrombopoiesis, we also hypothesised that a subgroup of diffuse cutaneous systemic sclerosis (dcSSc) patients with elevated platelet counts might have higher levels of IL-6.
This was a cross-sectional study of SSc patients and healthy controls. These include three subgroups of SSc cases: dcSSc with high platelets (n=20, mean platelet count: 458 × 109/L, IQR: 418508), dcSSc with normal platelets (n=19, mean platelet count: 276 × 109, IQR: 242313), limited cutaneous SSc(lcSSc) (n=22, mean platelet count: 264 × 109, IQR: 227297) and 15 controls. Serum IL-6 and soluble IL-6 receptor (sIL-6r) levels (in pg/ml) were determined by ELISA. Associations between serum IL-6 and CRP, platelet count, peak and concurrent skin score were determined by Pearson's correlation coefficient. IL-6 levels were subdivided into three categories: High (>10 pg/ml), Low (<10 pg/ml and > 3.12 pg/ml) and undetectable (below quantitation limit, < 3.12 pg/ml). Categorical data were analysed by Chi-square test.
A majority of the cases were female: 77% and 96% in dcSSc and lcSSc respectively compared to 53% in controls. The age of the subjects was similar in all cohorts (mean±SD, years): 55.1±10.3 dcSSc, 59.1±11.4 lcSSc and 53.7±11.4 controls. Duration of disease (mean±SEM,months) for lcSSc and dcSSc was 152.6±23.9 and 52.4±7.0 respectively. Disease duration (mean±SEM,months) was longer in dcSSc with elevated platelets (57.0±11.9) than those with normal platelets (47.3±6.9).
IL-6 levels were significantly elevated in 55% of the dcSSc cohort with thrombocytosis compared to only 21% of the dcSSc cohort with normal platelets (p<0.001). In contrast, a majority of the lcSSc (75%) and control (87%) cohorts had undetectable IL-6 levels. Moreover, IL-6 levels were positively correlated with platelet count in SSc (r=0.5, p<0.001). However, there were no significant differences in sIL-6R levels across all cohorts (p=0.16) and no correlation was observed between sIL-6R levels and platelet count (r=-0.15, p=0.23). There was strong association between serum IL-6 and CRP in the total cohort (r =0.74, p<0.001) and this correlation remained significant in the dcSSc with elevated platelets cohort (r =0.5, p<0.001). In addition, serum IL-6 levels positively correlate with concurrent mRSS (r=0.48, p=0.02) but not with peak mRSS (r=0.19, p=0.40). There was moderate correlation between platelet count and concurrent mRSS (r=0.33, p=0.05).
These results suggest that IL-6 may be a potential biomarker for skin disease in SSc and that thrombocytosis in dcSSc patients may selectively identify those with high IL-6, and higher mRSS. Together these data support further exploration of the pathogenic role of IL-6 in SSc and suggest that a targeted therapeutic strategy against IL-6 may be worthwhile.
To cite this abstract, please use the following information:
Ong, Voon, Nihtyanova, Svetlana, Black, Carol M., Denton, Christopher P.; A Clinically Defined Subset of dcSSc Is Associated with Elevated Serum IL-6 Level [abstract]. Arthritis Rheum 2009;60 Suppl 10 :440