Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus

Jack Godsell, Ina Rudloff, Rangi Kandane-Rathnayake, Alberta Hoi, Marcel F Nold, Eric F Morand, James Harris, Jack Godsell, Ina Rudloff, Rangi Kandane-Rathnayake, Alberta Hoi, Marcel F Nold, Eric F Morand, James Harris

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the development of autoantibodies to nuclear antigens and inflammatory responses mediated by multiple cytokines. Although previous studies have determined clinical associations between SLE and the anti-inflammatory cytokines IL-10 and IL-37, their role in the disease, or their potential as biomarkers, remains unclear. We examined serum levels of IL-10 and IL-37 in a large cohort of SLE patients, with detailed longitudinal clinical data. We demonstrate a statistically significant association of serum IL-10 with disease activity, with higher levels in active compared to inactive disease. High first visit IL-10 was predictive of high subsequent disease activity; patients with IL-10 in highest quartile at first visit were 3.6 times more likely to have active disease in subsequent visits. Serum IL-37 was also higher in SLE patients compared to control, and was strongly associated with Asian ethnicity. However, IL-37 was not statistically significantly associated with disease activity. IL-37 was significantly reduced in patients with organ damage but this association was attenuated in multivariable analysis. The data suggest that IL-10, but not IL-37, may have potential as a biomarker predictive for disease activity in SLE.

Figures

Figure 1. Serum IL-10 is increased in…
Figure 1. Serum IL-10 is increased in SLE and active disease.
Serum levels of (A) IL-10 and (B) IL-37, measured by ELISA, in patients with SLE, compared with healthy controls. Correlations graphs of (C) First visit IL-10 and (D) IL-10 from all visits with SLEDAI-2k. (E) Comparison of Serum IL-10 in patients with inactive (SLEDAI-2k < 4) or active disease (SLEDAI-2k > 4) (F) Comparison of serum IL-37 levels in patients with inactive or active disease. The horizontal line in each dot plot depicts the median.
Figure 2. Serum IL-10 is correlated with…
Figure 2. Serum IL-10 is correlated with longitudinal assessments of disease activity in SLE.
(A) Correlation between time-adjusted mean (TAM) serum IL-10 and time adjusted mean SLEDAI-2k (AMS). (B) comparison of TAM IL-10 in serum from patients with or without persistently active disease (PAD), measured by ELISA. (C) Correlation between first visit serum IL-10 with AMS. (D) Comparison of first visit IL-10 in serum from patients with or without persistently active disease (PAD), measured by ELISA. The horizontal line in each dot plot depicts the median.
Figure 3. Associations of serum IL-10 with…
Figure 3. Associations of serum IL-10 with organ-specific disease activity in SLE.
Geometric mean concentrations of IL-10 (with corresponding 95% confidnece interval in pg/mL), derived from univariable linear regression analyses by organ-specific disease; (A) Central nervous system (CNS) activity, (B) vasculitis (VAS), (C) musculoskeletal (MSK) activity, (D) renal activity, (E) Cutaneous (CUT) disease, (F) Serositis (SER), (G) Serological (Serol.) activity, (H) Fever, (I) Heamatological (Heam.) activity. Values are geometric means.

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