OP0195 PLASMA CHECKPOINT PROTEIN LEVELS AND GALECTIN-9 IN JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: E. Sag, K. Yüksel, S. Demir, S. Ozdel, U. Kaya Akca, E. Atalay, M. Kasap-Cuceoglu, R. Topaloglu, Y. Bilginer, S. Özen
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic Lupus Erythematosus (SLE) is the prototype for a systemic autoimmune disease. SLE is a disease of the adaptive immune system where T lymphocyte dysfunction has an important role as well. Checkpoint proteins have become an important topic in the study of Tcell. The balance of T cell co-stimulatory and co-inhibitory receptors is important for the regulation of the adaptive immune system response. Objectives: In this study we aimed to assess the checkpoint proteins in childhood SLE patients Methods: Fourty-nine jSLE patients together with 15 age- and gender- matched controls were included. Clinical features, disease activity scores and laboratory parameters were recorded both retrospectively and at the time of samplimg. Patient samples were collected at their last visit, Plasma CD25 (IL-2Rα), 4-1BB, B7.2 (CD86), TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG- 3, Galectin-9 levels were studied by the cytometric bead-based multiplex assay panel according to manufacturer’s instruction (LEGENDplex HU Immune Checkpoint Panel 1 (10-plex); catalogue number 740962, Biolegend) and analysed by Novocyte 3005 flow cytometer. Two-step cluster analysis procedure was conducted over the chosen 7 symptom status and 3 clusters were chosen for the final analysis Results: A total of 49 patients (71.4% female) diagnosed with SLE according to the SLICC criteria and 15 healthy controls (73.3% female) were included in the study. The mean age of the patients was 17.7 ± 2.6 years and the controls was 13.3±1.4 years. The median disease duration was 5.7 years. At the time of sampling fifteen of the patients had a SLEDAI score of zero (no activity), 21 of them had between 1-5 (mild activity), 7 of them had between 6-10 (moderate activity), 5 of them had between 11-19 (high activity), 1 of them had &gt;20 (very high activity). Galectin-9 and PD-L1 were significantly higher in SLE patients. Other checkpoint proteins and IL-2Rα were also higher but did not reach statistical significance. There were significant correlations between SLEDAI and IL-2Rα, Galectin-9 and PDL1. (Figure 1) There were three clinical clusters: Cluster 1 included patients with no major organ involvement, cluster 2 had predominantly haematological involvement (n=16) and cluster 3 (n=11) had predominantly renal involvement. Checkpoint proteins were not different among these three clusters. Figure 1. Table 1. Demographic, Clinical and Laboratory Features of Patients (n=49) Female gender, n (%) 35 (%71.4) Mean age at diagnosis, years (mean±SD) 12.5±3.3 Mean age at the time of inclusion, years (mean±SD) 17.7±2.6 Duration of illness, years (median/IQR) 5.7 (3.0-7.0) years Active system involvement at study, n (%) Renal 14 (28.5) Skin 11 (22.4) Musculoskeletal 9 (18.3) Hematologic 9 (18.3) Neurologic 1 (2.0) Serositis 1 (2.0) Laboratory findings (median/minimum-maximum) Hemoglobin, gr/dl 12.7 (7.3-18.3) WBC, /mm 3 6.900 (2.600-26.200) Platelet, /mm 3 252.000 (39.000-529.000) Erythrocyte sedimentation rate, mm/hour 10 (1-71) C-reactive protein, mg/dl 0.1 (0-21.1) Complement 3, mg/dl 87.6 (25.4-186.0) Complement 4, mg/dl 15.3 (0-45.8) Anti-ds DNA, IU/ml 12.8 (0-741.7) SLEDAI score (mean±SD) 4.69±6.69 Conclusion: Our data supports that Galectin 9 and IL-2Rα are good markers for disease activity in childhood SLE. We need larger series to evaluate differences between disease clusters in SLE. We failed to show a significant correlation with checkpoint proteins and SLEDAI except for PDL1. References: [1]Sharabi A and Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy. Nature reviews Rheumatology 2020; 16: 100-112 [2]Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 141-151. [3]McKinney EF, Lee JC, Jayne DR, et al. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 2015 [4]Wherry EJ and Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15: 486-499 Disclosure of Interests: None declared