Abstract
ObjectivesMacrophage migration inhibitory factor (MIF) and D‐dopachrome tautomerase (DDT), members of the same cytokine superfamily, are linked to the pathogenesis of a number of inflammatory diseases. The aim of this study was to investigate their clinical relevance in systemic sclerosis (SSc).MethodsSerum MIF and DDT were quantified in 105 SSc patients by ELISA and levels compared to healthy controls (HC) (47) and patients with systemic lupus erythematosus (SLE) (184). Clinical parameters included organ involvement, serum laboratory markers and results of pulmonary function tests, and overall disease activity assessed using the European Scleroderma Trials and Research group (EUSTAR) activity index.ResultsThere was no significant difference in serum DDT concentrations between patients with SSc and HC. However, serum MIF was significantly increased in SSc compared to both HC and SLE cohorts. Serum MIF was increased in SSc patients with low forced vital capacity (FVC) and was also associated with the use of angiotensin II receptor blockers and beta blockers in SSc, confirmed after adjusting for the presence of systemic hypertension and low FVC. Serum DDT was significantly higher in SSc patients with low FEV1 and negatively correlated with EUSTAR score, particularly in patients with limited disease.ConclusionAlthough not significantly linked to specific clinical parameters, serum MIF was significantly higher in SSc patients than in HC and SLE patients, suggesting a fundamental role for MIF in SSc. DDT, while closely related to MIF, did not show a similar expression profile, suggesting functional differences between these molecules.
Highlights
Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem autoimmune disease characterised by fibrosis, vascular dysfunction and immune dysregulation, notable for its biological and clinical heterogeneity.[1,2] While genetic and environmental factors are implicated in systemic sclerosis (SSc) disease progression, there is increasing evidence to support a role for dysregulation of the innate immune system in SSc pathogenesis.[1,2]Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory molecule with a broad range of immunomodulatory properties.[3]
While a small number of studies have examined the potential role of MIF in the pathogenesis of SSc,[7,9,10,13,14,15] no prior published study has investigated D-dopachrome tautomerase (DDT) in SSc
We examined concentrations of serum MIF and DDT in SSc and healthy controls (HC), in order to determine their clinical associations in SSc
Summary
Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem autoimmune disease characterised by fibrosis, vascular dysfunction and immune dysregulation, notable for its biological and clinical heterogeneity.[1,2] While genetic and environmental factors are implicated in SSc disease progression, there is increasing evidence to support a role for dysregulation of the innate immune system in SSc pathogenesis.[1,2]. Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory molecule with a broad range of immunomodulatory properties.[3] MIF has been shown to play a role in disease progression of autoimmune and inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease and multiple sclerosis.[3,4,5] Studies have suggested possible associations between MIF and SSc, but the relationship between the two is unclear.
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