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Background The antimalarial drug hydroxychloroquine (HCQ) is used worldwide to control the disease activity of systemic lupus erythematosus (SLE). In Japan, HCQ was not approved until September 2015 due to the problem of retinopathy induced by chloroquine. There is insufficient evidence of the effects of HCQ or adverse events linked to HCQ treatment. Objectives Here, we evaluated adverse events and the relapse risk of SLE during HCQ treatment. Methods We retrospectively analyzed the data of 109 patients diagnosed with SLE and treated with HCQ for ≥12 months at Nagasaki University Hospital and community hospitals. The demographic data included the patient‘s age at the onset of SLE, gender, the disease duration of SLE (the time from the diagnosis of SLE until the renal biopsy), comorbidities of Sjogren syndrome (SS)/anti-phospholipid syndrome (APS), and the treatment for induction. We identified the risk of adverse events and relapse at 12 months after the introduction of HCQ. Decision tree models predicting relapse were built with the Classification and Regression Trees (CART) algorithm. The data of the length of time between a patient‘s HCQ induction to the first observation of relapse was analyzed by the Kaplan-Meier method with a log-rank test. Results Most of the patients were female (88.1%). The median age at the introduction of HCQ was 40.0 years (interquartile range [IQR] 30.5–50.0 years), and the SLE disease duration was 95 months (IQR 38.0–184.5 months). The mean observation period after HCQ introduction was 12 months. The comorbidity rates of SS and APS were 25.7% and 20.2%, respectively. The SELENA-SLEDAI scores were significantly decreased at 3 months post-HCQ introduction. The dose of oral prednisolone was significantly decreased at 6 months post-HCQ introduction. Eighty-six patients (78.9%) were continuing HCQ at 12 months post-introduction. Adverse events occurred in 27 patients (24.8%), including skin rashes (n=11, 10.1%) and gastrointestinal symptoms (n=6, 5.5%). The sole predictive factor for adverse events was the white blood cell (WBC) count at baseline (odds ratio: 0.9997, 95%CI: 0.9994–0.9999, p=0.0285). Twelve of 86 patients (14.0%) experienced relapse that required the start of prednisolone or an immunosuppressant or an increased prednisolone dose. The multivariate analysis revealed that the C4 value at baseline was a predictive factor of relapse (odds ratio: 0.841, 95%CI: 0.718–0.984, p=0.0097). The cut-off point determined by the CART algorithm showed that C4 ≥9.3 mg/dl at baseline provides the best performance for predicting relapse. The Kaplan-Meier analysis showed that compared to C4 Conclusion A lower C4 value at HCQ introduction was a predictive factor for the relapse of SLE, and a lower WBC count was a predictive factor for adverse events. References [1] Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017 Mar;16(3):411-419. doi: 10.1080/14740338.2017.1269168. Disclosure of Interests None declared

Background Systemic lupus erythematosus (SLE) is multisystem disorder that is caused by tissue damage resulting from antibody and complement-fixing immune complex deposition. Lupus nephritis (LN) is frequent complication and one of the most serious manifestations of SLE. The expression of nephrin, as podocyte marker, is reduced in various renal diseases that develop into nephrotic syndrome1). The alteration of the structural protein in podocytes is known as a mechanism of proteinuria in LN. Objectives The signaling lymphocyte activation molecule family (the SLAM family) of type I transmembrane receptors consists of nine related members of the immunoglobulin superfamily and has been reported to mediate important regulatory signals between immune cells through their homophilic and heterophilic interactions2).The 1q23 region (Sle1b region in mouse) on human chromosome 1 including the SLAMF cluster of genes, containing SLAMF6 has been identified as a lupus susceptibility locus3).It has been shown that the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) is enhanced in CD4+T cells of SLE patients and is involved in IL-17 production4). We sought to examine the functional role of SLAMF6 in lupus podocytes. Methods We evaluated the co-expression of nephrin, a podocyte marker and SLAMF6 in kidney of normal controls and LN patients, also in B6 and MRL/lpr mice at the age of 8wk and 16wk by immunofluorescence analysis. We also examined nephrin positive SLAMF6 expression in isolated podocytes from B6 and MRL/lpr kidneys. Then, we analyzed the expression of SLAMF6 in CD4+T cells of isolated kidney and spleen in B6 and MRL/lpr mice. We treated human podocytes with IgG from healthy individuals and LN patients for 24 h and 48h and analyzed the expression of SLAMF6 by real-time PCR. Results In the histopathology, the expression of SLAMF6 was increased in nephrin positive area in LN patients and MRL/lpr mice compared to each control groups. Although the expression of nephrin in MRL/lpr mice kidney at 16 wk old decreased compared to B6 mice at same age, the expression of SLAMF6 in podocytes increased in diseased MRL/lpr mice compared to B6 mice. Similarly, the expression of SLAMF6 in CD4+ T cells increased in diseased MRL/lpr mice kidney and spleen compared to B6 mice. The level of SLAMF6 mRNA elevated in human podocytes exposed to LN-derived IgG compared to healthy individuals-derived IgG. Conclusion The expression of SLAMF6 is enhanced in LN podocytes, suggesting that the possibility of cooperating with CD4+T cells contributing to its dysfunction. Further examination is needed to investigate in detail how SLAMF6 is involved in the development of LN in the future. References [1] J Am Soc Nephrol. 2003Aug;14(8):2063-71., [2] Nat Rev Immunol. 2003Oct;3(10):813-21., [3] Nat Rev Rheumatol. 2010Jun;6(6):348-57., [4] J Immunol2012; 188:1206-1212. Disclosure of Interests Takashi Igawa: None declared, Kunihiro Ichinose: None declared, Mizuna Eguchi: None declared, Momoko Okamoto: None declared, Yushiro Endo: None declared, Sousuke Tsuji: None declared, Ayuko Takatani: None declared, Toshimasa Shimizu: None declared, Remi Sumiyoshi: None declared, Tomohiro Koga: None declared, Shin-ya Kawashiri: None declared, Naoki Iwamoto: None declared, Mami Tamai: None declared, Hideki Nakamura: None declared, Tomoki Origuchi: None declared, Atsushi Kawakami Grant/research support from: Astellas Pharma, Consultant for: Astellas Pharma, Speakers bureau: Astellas Pharma