John Mountz, CommitteeAlduraibi , Fatima K2025-03-112022NAhttps://digitalcommons.library.uab.edu/etd-collection/206https://hdl.handle.net/20.500.14154/75001Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease charac-terized by production of autoantibodies (autoAbs) and cytokines. Moreover, lupus nephritis (LN) occurs in approximately 50% of SLE patients. AutoAb and cytokine levels produced by B and T cells are high in LN patients, although their relationship with histological patterns requires inves-tigation. Methods: We analyzed the relationship between B cell cytokines and major T cell cyto-kines, including their association with autoAbs, and the clinical manifestations of SLE, espe-cially LN. We also analyzed endogenous intracellular interferon beta (IFNβ) expression in the peripheral blood mononuclear cells and serum circulating nephritogenic autoAbs from patients with SLE (n = 80) and healthy controls (n = 16). Subsequently, plasma levels of T-helper cell cy-tokines and autoAbs were determined in patients with SLE (n = 60) and healthy controls (n = 11). Results: IFNβ expression was significantly higher in patients with SLE than in healthy controls (HC; P < 0.001) and positively associated with LN (P = 0.008) but not cutaneous mani-festations. Additionally, it was associated with increased circulating IgG anti-DNA and IgG anti- ii Smith autoAbs (P = 0.0130, P = 0.0010, respectively), and elevated urinary protein/creatinine ra-tio (P = 0.064). Histopathological evaluation of kidney biopsies revealed that higher IFNβ levels correlated with severe LN—higher degree of activity and chronicity (P < 0.0001, P = 0.0225 and P = 0.0327, respectively). Immune complex deposition in the kidney was not associated with in-creased IFNβ. Interferon gamma (IFNɣ) and interleukin (IL)-17 were generalized features in pa-tients with SLE. However, higher IL-10 levels occurred in patients with LN. IL-17 levels were significantly higher in patients with LN class V and discoid lupus (P = 0.0055 and P = 0.0238, respectively). IFNɣ was positively correlated with anti-double stranded DNA and anti-Sjogren's syndrome A (P = 0.0355 and p = 0.0402, respectively), while IL-17 was correlated with anti-Ro/SSA (P = 0.0130). Conclusions: IFNβ represents a potential biomarker for LN, while IL-10 and IL-17 could be used in combination with other diagnostic markers. Our results show the pathogenic mecha-nisms underlying LN to guide diagnosis and therapy.155en-USSystemic lupus erythematosuslupus nephritisautoantibodiesIL-17IL-10IFNβThesis