Background/Purpose:  Currently available clinical biomarkers are not reliable predictors of long-term progression of interstitial lung disease (ILD) in the context of systemic sclerosis (SSc) A previous study of the GENISOS cohort demonstrated that higher plasma MCP-1 (CCL2) predicted a more rapid decline of forced vital capacity (FVC) while IL-10 levels were protective. IL-6 has also been proposed as a cytokine predictive for SSc-ILD progression (De Lauretis et al. J Rheumatol. 2013). Herein, we determined the predictive significance of baseline serum MCP-1, IL-10 and IL-6 levels for progression of ILD and survival in an independent cohort of patients with early SSc.

Methods:  Baseline serum samples of SSc patients with disease duration < 5 years enrolled in the Canadian Scleroderma Research Group were investigated. Samples were collected according to a common standard operating procedure. The serum levels of 3 key cytokines MCP-1, IL-10 and IL-6 were determined by highly sensitive Mesoscale assays (Meso Scale Discovery, Rockville, MA). The primary outcome was decline in forced vital capacity (FVC% predicted) over time. The rate of change in a longitudinally obtained FVC % predicted value was investigated by a joint analysis of longitudinal measurements (sequentially obtained FVC% predicted) and Cox regression for survival. This approach allows inclusion of all FVC measurements and accounts for dependency on survival. Cytokines were analyzed as log-transformed continuous variable.

Results:  A total of 190 patients with early SSc were investigated. The proportion of female patients was 82% (n=156) and diffuse skin involvement was present in 40% (n=76) patients. The mean disease duration at enrollment was 2.2 years and mean follow-up time was 5.72 years. 19 patients (10%) died during follow-up period. After adjustment for age, gender and ethnicity, there was a trend for an association between higher levels of MCP-1 and faster FVC decline (b=-0.50, 95% CI: -1.54; 0.04, p=0.072) while IL-6 and IL-10 levels were not predictive of differential rate of FVC decline (p=0.109 and p=0.679, respectively). When the model was additionally adjusted for treatment with immunosuppression and disease subtype, the relationship between baseline serum MCP-1 levels and long-term decline in FVC became significant (b=-0.54, 95% CI:-1.08; -0.00, p=0.048). IL-10 and IL-6 also did not show predictive significance in the expanded model (p=0.571 and p=0.116, respectively). Higher serum MCP-1 levels was also associated with poorer survival (HR: 5.31, 95% CI: 1.45; 19.43, p= 0.012).

Conclusion:  We confirmed MCP-1 is an important biomarker predictive of ILD progression and poorer survival in SSc. MCP-1 might aid in informing clinical decisions and enrichment strategies for clinical trials. Furthermore, these data supports MCP-1, a marker of pro-fibrotic macrophages as an important treatment target in SSc-ILD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-mcp-1-levels-predict-long-term-progression-of-interstitial-lung-disease-in-systemic-sclerosis/