Background/Purpose:

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. 

Methods:

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. 

Results:

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.

Conclusion:

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.

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/