Ab0118 diagnostic predictive value of soluble psgl-1 and their ligands in patients with systemic lupus erythematosus (sle)

Background Rheumatic diseases are generally diagnosed in advanced stages. Systemic lupus erythematosus (SLE) are systemic inflammatory autoimmune disease characterized by presence of autoantibodies against DNA and nuclear proteins and a wide variety of clinical symptoms (Fava 2019, Wang 2019 ). Actually, it has not curative treatment (Mathias 2020 ). Therefore, the search for biomarkers for SLE diagnosis in earlier stages and its derived complications is mandatory (Thanou 2021, Wan 2018 ). Adhesion molecules are crucial to leukocytes infiltration to inflammation sites (Ponthieux 2004, Ivetic 2019, Tinoco 2017 ), thus they play an important role in autoimmune diseases and have been suggested as a useful markers of diagnosis and prognosis in rheumatic disease (Gonzalez-Tajuelo 2017, Skeoch 2014, da Rosa Franchi 2018 ). Objectives To study the possible involvement of adhesion molecules in the development of disease, we have analysed the pattern of PSGL-1 serum levels together with its main ligands P- E- and L-selectins and ADAM8 in SLE patients. Methods Serum samples from 52 SLE patients, 36 inactive (iSLE) and 16 active (aSLE) and 55 healthy donors (HD) sex and age matched per group were collected and proteins levels were measured by available ELISA kits: Human PSGL-1/CD162 kit (Novus Biologicals, Colorado, USA), Human Selectins/CD62 kits CD62E, CD62L and CD62P (Diaclone, France), and Human ADAM8 (A Disintegrin And Metalloprotease 8) Kit (Elabscience, Texas, USA). Results SLE patients showed a statistically significant increase of PSGL-1, E-Selectin and ADAM8 and decrease of L-Selectin serum levels with respect to HD. No difference were observed between inactive and active SLE patients. Patients with anti-dsDNA and/or anti-SSA autoantibodies showed lower serum level of PSGL-1 and higher level of L-Selectin and ADAM8 compared to patients with absence of these autoantibodies. Importantly, the expression profile study of these proteins revealed that L-Selectin/ADAM8 ratio in SLE patients is a good predicted marker in a multivariable binary logistic regression model (OR=1,701, CI:1,188-2,450, p<0.005). Receiver operating characteristic (ROC) curve presented an area under curve (AUC) of 0.80 and the optimal cut off value maximizing sensitivity (98%) and specificity (48%) jointly corresponded to ratio<2,06. In this model the 97% of patients were correctly grouped. Conclusion SLE patients show significantly different serum levels of PSGL-1, E-Selectin, L-Selectin and ADAM8 with respect to healthy controls. This specific profile of serum protein levels could be a potentially valuable tool for the early diagnosis of SLE. References [1] Fava A et all. Journal of Autoimmunity 2019 Jan; 96:1-13. [2] González-Tajuelo R et all. Frontiers in Immunology 2020 Nov 12;11:588212 [3] Ivetic A et all. Frontiers in Immunology 2019 (10): Article 1068 (pag 1-22) [4] Mathias LM et all. Expert Opinnion Therapy Targets 2020 Dec; 24 (12): 1283-1302 [5] Ponthieux A et all. Atherosclerosis 2004 172: 299–308 [6] da Rosa Franchi-Santos LF et all. Lupus 2018 Mar; 27(3):380-388. [7] Skeoch S et all. Lupus 2014 Jul; 23(8):819-24 [8] Thanou A et all. Journal of Autoimmunity 2021 May; 119:102615. [9] Tinoco R et all. Trends in Immunology 2017 May; 38(5): 323–335. [10] Wan L et all. J of Clinical Laboratory Analysis 2018 May; 32(4):e22361 [11] Wang X et all. Frontiers in Immunology 2019 Jul 17; 10:1667. Acknowledgements This work was supported by the Spanish Ministry of Health and ISCIII (co-financed by Fondos FEDER) (FIS-PI17-01819, FIS-PI20-01690 and by the project “Molecular stratification of patients with giant cell arteritis to tailor glucocorticoid and tocilizumab therapy (START Project)”, funded by FOREUM, Foundation for Research in Rheumatology. Disclosure of Interests None Declared.