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
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.
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.
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).
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