title: Association of MIF, but not type I interferon-induced chemokines, with increased disease activity in Asian patients with systemic lupus erythematosus.
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.
authors.affiliation: Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: K L
authors.initials: KL
authors.lastname: Connelly
authors.affiliation: Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Kandane-Rathnayake
authors.affiliation: Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Hoi
authors.affiliation: Department of Medicine and Rheumatology, The University of Melbourne at St. Vincent's Hospital, Melbourne, Australia.
authors.forename: Mandana
authors.initials: M
authors.lastname: Nikpour
authors.affiliation: Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors.forename: E F
authors.initials: EF
authors.lastname: Morand
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D054415:Chemokine CCL19 / Q000097:blood / Q000235:genetics; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000235:genetics*; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C515460:CCL19 protein, human; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D007370:Interferon Type I; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human