THU0273 Decreased Interleukin-35 Is Associated with Higher Risk of Pregnancy Morbidity in Patients with Antiphospholipid Syndrome
Authors: N. Liu, S. Zhang, C. Li, H. Zhu, A. Al-Hussaini, X. Wei, X. Zhang, L. Zhu, Q. Lu, R. Mu, Z. Li
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Antiphospholipid syndrome (APS) is an autoimmune disease characterized mainly by recurrent pregnancy failures and/or thrombosis <sup>1</sup>. Interleukin (IL)-35, a new member of IL-12 family, was demonstrated to play a role in the immunopathogenesis of several autoimmune diseases <sup>2,3</sup>. The expression of IL-35 was observed to be abnormal in idiopathic recurrent pregnancy loss <sup>4</sup>. <h3>Objectives</h3> To determine the expression of IL-35 and assess its association with clinical /laboratory features in patients with APS. <h3>Methods</h3> Serum IL-35 was detected by the enzyme-linked immunosorbent assay (ELISA). 126 patients with APS, 38 patients with primary pregnancy morbidity, and 69 healthy controls were enrolled in the study. Clinical and laboratory features of APS patients were recorded. The Mann-Whitney U test was used to evaluate differences of non-normal distribution data and the Student9s t test was used for normal distribution data. The differences in the frequency of clinical /laboratory characteristics were assessed by the Chi-square (χ<sup>2</sup>) test. The relevances between IL-35 and clinical/laboratory features were further analyzed by the Spearman test (measurement data) or Chi-square (χ<sup>2</sup>) test (qualitative data). <h3>Results</h3> Serum IL-35 was significantly decreased in APS patients (median 14.73, IQR 0–28.09 pg/ml) and patients with primary pregnancy morbidity (16.00, 10.56–25.00 pg/ml), compared to healthy controls (28.87, 20.16–47.47 pg/ml; all <i>p</i>&lt;0.001). Female APS patients with decreased IL-35 had higher risk of pregnancy morbidity than those with normal IL-35, with an odds ratio (OR) of 2.565 (95% confidence interval (CI) 1.138–5.785, <i>p</i>=0.022), especially events of fetus death ≥ the 10th week (OR=6.545, 95% CI 6.03–21.101; <i>p</i>&lt;0.001). In contrast, the frequency of thrombosis was significantly lower in APS patients with decreased IL-35 and the OR value was 0.382 (0.185- 0.789; <i>p</i>=0.009). <h3>Conclusions</h3> Serum IL-35 was decreased in APS patients and was associated with pregnancy morbidity and thrombosis, raising the hypothesis of its complicated pathogenic roles in APS. <h3>References</h3> Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295–306. Niedbala W, Wei XQ, Cai B, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol 2007;37:3021–9. Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007;450:566–9. Ozkan ZS, Deveci D, Simsek M, et al. What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss? J Matern Fetal Neonatal Med 2015;28:324–8. <h3>Acknowledgement</h3> This study was funded by the 973 program of China (No. 2012CB517702) and National Natural Science Foundation of China (No. 81471536). We thank all co-authors for their contribution to this work. We also thank all patients and healthy donors whom took part in this study. <h3>Disclosure of Interest</h3> None declared