Ab1062 Correlation Between Cytokines and Clinical Parameters in Patients With Active Sle -Subgroup Analysis Using Interferon Alpha, Interleukin 6 and Interferon Gamma

Background: Type I interferon (IFN), especially IFN-alpha, is a key cytokine in the pathogenesis of systemic lupus erythematosus (SLE). However, serum IFN-alpha can be detected in only about half of active SLE patients. We previously reported that various cytokines can be detected in the sera of IFN alpha-negative SLE patients, and these patients were very heterogeneous. For example, some patients produce only IL-6 and IL-1, and some produce high amounts of IFN-gamma but not IFN-alpha. We hypothesized that there are key cytokines that drive SLE pathogenesis in each patient, and that organ involvement may be determined by the combination of specific cytokines. Objectives: The aim of this study was to determine the correlation between cytokines and clinical characteristics, and to stratify SLE patients by cytokines, especially in IFN alpha-negative SLE patients. Methods: Patients with SLE were recruited at Kyoto University Hospital between 2000 and 2018. Stored sera from 58 untreated active Japanese patients with SLE were assayed for various cytokines using a cytokine bead array (Procarta Cytokine Assay Kit). Twenty-six clinical indices, including affected organs, serological findings, and activity index (SLEDAI), were collected from the chart. The correlation between each clinical parameter and cytokine was evaluated using Fisher's exact test. Each parameter position was determined so that those that were more strongly correlated with each other were closer using the Fruchterman–Reingold algorithm implemented in the Network X package (ver. 2.1) in Python. The clinical characteristics of each stratified group were compared between groups using one-way ANOVA or chi-squared test. Results: The association between each cytokine level and clinical parameter is shown in Figure 1. Among cytokines, a correlation was observed between IL-6 and IL-1b, as well as among TNF alpha, IL-4, IL-10, IL-21, IFN gamma, IL-17a, and sCD40. IFN alpha was not strongly associated with these two cytokine clusters. A correlation was detected between CNS symptoms and IL-1 beta (p=0.0037), and between fever and IFN alpha (0.0031). A correlation between low complement and IFN-alpha was also observed (p=0.0058). Since there seemed to be three cytokine clusters, we selected three representative cytokines: IFN alpha, IL-6, and IFN gamma. As shown in Table 1, we compared the clinical characteristics among four distinct groups: Group 1, IFN alpha (+); Group 2, IFN alpha (-) IL-6 (+); Group 3, IFN alpha (-) IL-6 (-) IFN gamma (+); and Group 4, IFN alpha (-) IL-6 (-) IFN gamma (-). Group 1 is characterized by fever, skin involvement, high anti-DNA antibody titers, and low complement levels. Group 2 was characterized by serositis and relatively high CRP levels. Groups 2 and 3 had relatively low disease activity and less frequently involved renal and skin lesions. Interestingly, Group 4 showed high disease activity and a higher frequency of renal involvement despite relatively low anti-DNA antibody titers and higher complement levels. Conclusion: We found three distinct cytokine clusters, and the combination of these cytokines may partially explain the pathogenesis of individual SLE patients. These findings will facilitate future molecular targeted therapies in personalized medicine. The average SLEDAI score, anti-DNA Ab titer, C3 complement level, and CRP level are shown in each group, and p-values were obtained by one-way ANOVA. The percentage of patients with organ involvement for fever, renal, skin, joint, central nervous system (CNS), hematological abnormality (Hemato), and serositis are shown, and p-values were obtained using the chi-squared test. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Koichiro Ohmura Eisai, Gilead Sciences, AstraZeneca, GSK, Asahi Kasei Pharma, Asahi Kasei Pharma, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma, Takeshi Iwasaki: None declared, Hideki Oka: None declared, Shuji Sumitomo Asahi-kasei, GSK, AstaraZeneca, Abbvie, Pfizer, Eli Lilly, Chugai, Astellas, BMS, Eizai, Mitsubishi-Tanabe, Akio Morinobu: None declared.