Background/Purpose:

Expression array studies suggest the activity of Type I interferon (IFN), as reflected in IFN-induced genes, is associated with phenotypic subsets in SLE. Three chemokines (CK) CCL2, CCL19, and CXCL10 induced by IFN are measurable in serum, and these have been correlated with IFN-induced gene expression and with SLE disease activity. Previous studies of clinical associations of IFN-induced CK were in patients with mild disease, were of short duration (<1y), and did not include Asian patients or analyse for the effects of glucocorticoids. We explored disease associations of IFN-CK in an SLE cohort followed for longer time periods and which included patients with more severe disease and Asians. 

Methods:

SLE patients (ACR criteria) attending a single centre between 2007-2012 had prospective recording of disease activity (SLEDAI-2k) at each visit and annual recording of organ damage (SLICC SDI). CCL2, CCL19, and CXCL10 were measured in matching serum samples by ELISA, and an integrated score (IFN-CK) (Bauer et al 2009) calculated.

Results:

1002 serum samples from 151 patients were analysed over a median (range) followup of 5 (1-27) visits over 2.75 (0 – 4.6) years. Patients were 84% female, 40% Asian ethnicity, median age 42y and disease duration 8.6y, median (range) SLEDAI 4 (0 – 22)) and time-adjusted mean SLEDAI (AMS) 4 (0 – 15). The individual chemokines CCL2, CCL19, and CXCL10 were highly correlated (P<0.0001). IFN-CK score exhibited a significant positive correlation with ESR and anti-dsDNA, and a significant negative correlation with C3 and C4. IFN-CK was significantly higher in active disease (SLEDAI>4) (P<0.0001), and accordingly SLEDAI was significantly higher in patients with high IFN-CK (P<0.001). Changes in IFN-CK and SLEDAI over time were also correlated (P=0.013), as were AMS and time-adjusted mean IFN-CK (P=0.008). Moreover, IFN-CK at baseline was correlated with subsequent disease activity as measured by AMS (P=0.04), and episodes of persistent active disease were 2-fold more likely during the period of observation in patients with high time-adjusted mean IFN-CK (RR = 2.05 (95% CI 1.06 – 3.99), P=0.0192). Patients who experienced an increase in SDI over the study period had significantly higher time-adjusted mean IFN-CK than those with no change in SDI. High IFN-CK was not associated with the presence of renal or CNS disease, but was associated with anti-ENA and dsDNA positivity (both P=0.02). Clinical associations of IFN-CK were more robust in the subset of patients of Asian ethnicity, but were less robust in patients on glucocorticoid therapy. 

Conclusion:

In a longitudinal cohort of SLE patients with severe disease, serum IFN-CK was strongly associated with indices of current and subsequent disease activity and damage. The associations between IFN-CK and disease activity were stronger in Asian SLE patients but were negatively influenced by glucocorticoids. Serum IFN-CK measurements appear to be a robust marker of disease activity in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-concentrations-of-type-i-interferon-regulated-chemokines-are-associated-with-disease-activity-in-systemic-lupus-erythematosus/