Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Association of MIF with Disease Activity, Damage, and Serum IL17 and IL6 in Systemic Lupus Erythematosus

Morand,  Eric F., Northcott,  Melissa, Kitching,  A. Richard, Brown,  Fiona, Hoi,  Alberta

Purpose:

MIF is a broad-spectrum pro-inflammatory protein with actions in T cells, B cells, macrophages and endothelial cells. MIF-deficiency is protective in MRL/lpr mice, and a single nucleotide polymorphism (SNP) at position -173 in the MIF promoter (rs755622) is associated with increased SLE susceptibility. Associations between MIF and disease manifestations in SLE have not been reported. We examined these associations prospectively.

Method:

Patients of the Monash Lupus clinic in Melbourne Australia have routine collection of disease activity (SELENA-SLEDAI) and serum at each visit. Damage (SLICC-ACR) is recorded annually. Serum MIF, IL6, and IL17 concentrations were measured by ELISA and genomic DNA was analysed for MIF -173 polymorphisms.

Results:

350 sera were analyzed from 97 subjects satisfying ACR criteria for SLE (mean (±SD) age 42 ± 14, disease duration 10 years ± 7.3, 78 female:17 male), followed over 17 ± 6 months. MIF was detected in all samples (median 3.1 ng/ml, mean (± SEM) 4.3 ± 0.2 ng/mL). SLEDAI varied during study (median (range) 5 (0 – 26)). Correlation between MIF and SLEDAI was not observed in the overall population, but in SLE patients without active renal disease, (renal SLEDAI = 0), a significant correlation between serum MIF and SLEDAI was observed (r = 0.16, p = 0.024). MIF genotype was analyzed in 81 patients, with the -173*C MIF allele being present in 21 patients (20 heterozygous, 1 homozygous). In patients with a disease duration > 10 years, the MIF -173*C allele was associated with significantly increased SLICC (3.0±0.68 vs 1.4±0.19, p =0.0274). No association between MIF genotype and SLEDAI or steroid exposure was detected. In samples in which IL17 was above assay detection limit (16ng/mL, n = 131), a significant correlation between MIF and IL17 was present (r = 0.36, p <0.0001). Serum MIF and IL-6 were also significantly correlated (r = 0.18, p = 0.0007). Consistent with this, samples in which MIF concentration was >1SD above the mean were characterized by higher mean IL17 (338±135 pg/mL vs 144±21, p=0.0166) and IL6 (180±73 pg/mL vs 62±12, p=0.0088).

Conclusion:

Serum MIF correlates with disease activity, and with serum IL17 and IL6, in SLE, and a MIF overexpression polymorphism is associated with increased disease-related damage in longstanding SLE. These results further support the potential role of MIF in the pathogenesis of SLE, and as a biomarker and outcome predictor. Moreover, these findings suggest the ability of MIF to regulate IL-17 and IL6 expression in SLE.

To cite this abstract, please use the following information:
Morand, Eric F., Northcott, Melissa, Kitching, A. Richard, Brown, Fiona, Hoi, Alberta; Association of MIF with Disease Activity, Damage, and Serum IL17 and IL6 in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1758
DOI: 10.1002/art.26832

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