Session Type: Abstract Submissions (ACR)
Chronic inflammation is believed to be responsible for accelerated atherosclerotic cardiovascular disease (CVD) in patients with SLE. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule implicated in the etiology of both SLE and atherosclerosis via amplification of macrophage recruitment and activation. A single nucleotide polymorphism (SNP) in the MIF promoter regulates MIF expression and is associated with SLE risk, and an anti-MIF therapy is currently in Phase I trials in SLE. The association of MIF polymorphisms with CVD risk in SLE is unknown.
SLE patients (ACR criteria) attending a single centre were recruited fo a pilot study. Patients seen between 2007-2012 had disease activity (SLEDAI-2k) recorded at each visit, and organ damage (SLICC-SDI) recorded at baseline and annually. CVD was defined using the cardiovascular domains of the SLICC-SDI criteria. Genomic DNA was isolated from whole blood, amplified by PCR, and MIF-173*C genotype determined by restriction fragment length polymorphism.
153 SLE patients (80% female, median age 41y, disease duration 10y) were studied. The median (range) SDI and time-adjusted mean SLEDAI (AMS) were 1 (0-9) and 4 (0-22) respectively.
The distribution of MIF-173 genotypes observed was G/G(69%) G/C(28%) and C/C(3%), thus a MIF-173C SNP was present in 31%. Organ damage (SDI) in the overall population correlated with disease duration (P<0.0001) and disease activity (AMS; P<0.0001). The major finding was that CVD was increased among patients carrying a MIF -173*C allele. Among patients with SLE duration >10y, CVD was 13-fold more frequent among patients carrying a MIF -173*C allele (odds ratio 12.75 (95%CI 2.2-75.2), p=0.0045). A significant association was also detected when stroke was included (OR=6.13, 95% CI 1.4-26.9, p=0.0204), and when AMI and/or stroke were analysed independently (OR=6.06, 95% CI 1.2-31.0, p=0.0375). There was no significant difference in traditional risk factors in relation to MIF -173*C allele, and no association detected with renal or CNS disease, corticosteroid use, or the frequency of episodes of persistently active disease.
Although confirmation in larger cohorts is required, this pilot study suggests that carriage of the MIF-173C SNP is strongly associated with the risk of CVD in SLE. This suggests that anti-MIF therapy could alleviate SLE CVD risk in SLE.
E. F. Morand,
A. Y. Hoi,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-polymorphism-in-the-mif-gene-is-associated-with-cardiovascular-morbidity-in-systemic-lupus-erythematosus-a-pilot-study/