Abstract
Ethnicity is a key factor impacting on disease severity in SLE, but molecular mechanisms of these associations are unknown. Type I IFN and MIF have each been associated with SLE pathogenesis. We investigated whether increased SLE severity in Asian patients is associated with either MIF or Type I IFN. SLE patients (n = 151) had prospective recording of disease variables. Serum MIF, and a validated composite score of three Type I IFN-inducible chemokines (IFNCK:CCL2, CXCL10, CCL19) were measured. Associations of MIF and IFNCK score with disease activity were assessed, with persistent active disease (PAD) used as a marker of high disease activity over a median 2.6 years follow up. In univariable analysis, MIF, IFNCK score and Asian ethnicity were significantly associated with PAD. Asian ethnicity was associated with higher MIF but not IFNCK score. In multivariable logistic regression analysis, MIF (OR3.62 (95% CI 1.14,11.5), p = 0.03) and Asian ethnicity (OR3.00 (95% CI 1.39,6.46), p < 0.01) but not IFNCK were significantly associated with PAD. These results potentially support an effect of MIF, but not Type I IFN, in heightened SLE disease severity in Asian SLE. The associations of MIF and Asian ethnicity with PAD are at least partly independent.
Highlights
Systemic lupus erythematosus (SLE; lupus) is a chronic autoimmune disease characterised by immunologicallymediated inflammatory activity across multiple organ systems and the potential for irreversible end organ damage[1]
The study cohort was 84% female, with a median age at enrolment of 42 years, and 40% of patients were of Asian ethnicity; non-Asian patients were of majority European descent (Table 1)
The chemokines contributing to the IFNCK score were detectable in all samples (CCL2: range 3.3–7853 pg/mL; CXCL10: range 3.81–11227 pg/mL; CCL19: 5.6–10981 pg/mL)
Summary
Systemic lupus erythematosus (SLE; lupus) is a chronic autoimmune disease characterised by immunologicallymediated inflammatory activity across multiple organ systems and the potential for irreversible end organ damage[1]. Asian ethnicity has been linked to a more severe SLE phenotype, including higher frequency of renal disease, and serological manifestations (including anti-dsDNA, anti-Ro and anti-Sm positivity), and higher disease activity[2]. Type I interferons (IFN) such as IFN-α, and macrophage migration inhibitory factor (MIF), are cytokines that have been demonstrated in murine and human studies to be implicated in the pathogenesis of SLE, and have been the subject of clinical trials in SLE. The association of cytokines such as IFN-αand MIF with SLE phenotype raises the possibility that factors such as these are implicated in the increased SLE severity observed in Asian patients. The aim of this study was to investigate the associations of serum concentrations of MIF and a marker of Type I IFN activity with ethnicity and measures of disease severity, in a prospective, multi-ethnic lupus cohort. Our findings suggest that increased disease activity in Asian SLE patients is associated with increased serum MIF, but not with Type I IFN
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