AB0398 TNF-LIKE WEAK INDUCER OF APOPTOSIS / FGF INDUCIBLE MOLECULE 14 PATHWAY IN UNTREATED LUPUS NEPHRITIS: SERUM OR URINE TWEAK LEVELS MORE ACCURATE IN RELATION TO RENAL ACTIVITY?
Authors: M. Bekhit, N. Abaza, N. Kamel, M. Ossman, S. Saad El Din
Journal: Annals of the Rheumatic Diseases (2020)

Background: Lupus nephritis (LN) is one of the most serious manifestations of SLE, affecting 70% of patients and the most critical predictor of morbidity and mortality of the disease [1].Tumor necrosis factor-like weak inducer of apoptosis/ fibroblast growth factor inducible molecule 14 (TWEAK/Fn14) activation is involved in various pathological processes that occur locally in kidneys, facilitating the pathogenesis of LN [2]. Objectives: To assess serum and urine TWEAK levels as well as renal Fn14 expression in newly diagnosed patients with LN and its correlation to disease activity. Methods: The present study included 30 selected newly diagnosed previously untreated SLE patients divided into 2 groups; 15 patients with LN and 15 without LN as well as 30 age and sex matched healthy subjects who served as control group. Written consent was obtained from all patients and controls after a full explanation of the study. Clinical assessment of disease activity by SLE Disease activity index (SLEDAI) [3]. Lupus nephritis was assessed clinically with the renal SLE disease activity index (rSLEDAI).Indicated renal biopsies were taken from the patients with LN and were classified according to the International Society of Nephrology and the Renal Pathology Society (ISN/RPS) classification [4].Serum and urinary levels of TWEAK were measured for the patients and controls using enzyme-linked immunosorbent assay (ELISA). Fn 14 was examined in renal biopsies from LN group by immunohistochemistry. Results: A significantly higher uTWEAK level on comparing SLE patients with LN to those without LN and controls (F = 149.2, P &lt; 0.001). uTWEAK had a highly significant positive correlation with, proteinuria (r = 0.755, P &lt; 0.001), a significant positive correlation with SLEDAI and rSLEADI (r = 0.217, P &lt; 0.037) (r = 0.476, P &lt; 0.024) respectively. uTWEAK had a significant negative correlation with anti-dsDNA titres, C3 and C4 (r = -0.579, P &lt; 0.008) (r = -0.456, P &lt; 0.011) (r = -0.552, P &lt; 0.002). Although sTWEAK level was higher in SLE patients than controls, it was not found to be associated with the presence of LN (F = 4.963, P =0.012). Fn14 expression was detected in glomerular and tubular cells in LN patients. Expression of Fn14 in renal biopsies from LN patients was examined. Immunohistochemistry for Fn14 was detected in (A ) glomerular endothelial cells, (B, C ) some specimens showed moderate and intense staining for Fn14 in renal tubular cells. In the controls [renal biopsies from patients with renal cell carcinoma (D )], there was very slight staining for Fn14 in renal tubular cells. Conclusion: Urinary TWEAK is a specific and sensitive biomarker for detection of active LN in newly diagnosed untreated SLE patients. References: [1 ] Kwok SK and Tsokos GC. New insights into the role of renal resident cells in the pathogenesis of lupus nephritis. Korean J Intern Med 2018; 33 (2): 284-289. [2 ] Xia Y, Herlitz LC, Gindea S, Wen J, Pawar RD, Misharin A, et al. Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis. J Am Soc Nephrol 2015; 26(5):1053-1070. [3 ] Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, Derivation of the SLEDAI. A disease activity index of lupus patients. Arthritis Rheum 1992; 35: 630-40. [4 ] Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15(2): 241-250. Disclosure of Interests: None declared