Background/Purpose: Higher levels of CXCL10 and CXCL11 in patients with a very early diagnosis of systemic sclerosis (SSc) subsequently shifted to SSc were pointed out (1). An intriguing role of IL-33 in early SSc patients was also previously described (2).          

Methods: Serum levels of CXCL-10, CXCL-11 and IL-33 were measured in 30 undifferentiated connective tissue disease at risk for SSc (UCTD-risk-SSc) patients (3), otherwise referred to as very early-early SSc, and 34 healthy controls (HC) by multiplex suspension immunoassay. All UCTD-risk-SSc patients were followed-up for 36 (12-101) months.

Results: Serum levels of CXCL-10, CXCL-11 and IL-33 resulted higher in UCTD-risk-SSc patients as compared to HC (respectively: p< 0.001; p< 0.001 and p=0.07). UCTD-risk-SSc subsequently evolved to SSc showed higher baseline cytokines levels versus patients not evolved (CXCL10: p=0.05; p=0.04 and IL-33: p=0.03). At receiver operating characteristic (ROC) analysis the following cut-off values were able to discriminate patients evolving into SSc (CXCL-10 >34.47 pg/mL, area under the curve (AUC)=0.72, p=0.02 with 0.63 sensitivity (SE) and 0.82 specificity (SP); CXCL11 >42.38 pg/mL, AUC=0.73, p=0.02 with 0.84 SE and 0.54 SP; IL-33 >8.86 pg/mL, AUC=0.73, p=0.01 with 0.89 SE and 0.54 SP). In addition a baseline CXCL-11 value >45.21 pg/mL and IL-33 value >8.86 pg/mL were able to discriminate patients developing an interstitial lung disease (AUC=0.80, p< 0.001 with 1.0 SE and 0.56 SP and AUC=0.72, p=0.05 with 1.0 SE and 0.53 SP).

Conclusion: We confirmed the previous data on CXCL-10 and CXCL-11 and we first highlighted a potential role of IL-33 in predicting disease evolution.

References:

• Crescioli C, Corinaldesi C, Riccieri V, Raparelli V, Vasile M, Del Galdo F, Valesini G, Lenzi A, Basili S, Antinozzi C. Association of circulating CXCL10 and CXCL11 with systemic sclerosis. Ann Rheum Dis 2018; 77:1845-1846.
• Vettori S, Cuomo G, Iudici M, D’Abrosca V, Giacco V, Barra G, De Palma R, Valentini G. Early Systemic Sclerosis: Serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels. J Clin Immunol 2014; 34:663–668.
• Valentini G. Undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev 2015; 14:210-3.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/undifferentiated-connective-tissue-disease-at-risk-for-ssc-potential-role-of-circulating-cxcl-10-cxcl-11-and-il-33-in-predicting-disease-evolution/