Distinct Clinical Manifestations Associated with Autoantibodies and Cytokines in Systemic Lupus Erythematosus

Abstract

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies (autoAbs) and cytokines. Lupus nephritis (LN) occurs in approximately 50% of SLE patients, contributing to morbidity and mortality. The AutoAbs and cytokines produced by B and T cells are at high levels in LN patients, although their relationship with histological patterns requires investigation.

Methods: We analyzed the relationship between B cell cytokines and major T cell cytokines, including their association with autoAbs, as well as the clinical manifestations of SLE, especially LN. We also analyzed endogenous cell intracellular interferon beta (IFNβ) expression in peripheral blood mononuclear cells (PBMC) and serum circulating nephritogenic autoAbs from patients with SLE (n = 80) and healthy controls (n = 16). Then, we determined plasma levels of T-helper cell cytokines and autoAbs in patients with SLE (n = 60) and healthy controls (n = 11).

Results: IFNβ expression was significantly higher in patients with SLE compared to healthy controls (HC) [P < 0.001] and positively associated with LN [P = 0.008] but not with cutaneous manifestations. It was also associated with a higher level of circulating IgG Anti-DNA and IgG anti-Smith (Anit-Sm) autoAbs [P = 0.0130, P = 0.0010, respectively], and an elevated urinary protein/creatinine ratio [P = 0.064]. Histopathological evaluation of kidney biopsies revealed that higher IFNβ levels were correlated with a severe form of LN—a 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 increased IFNβ. Interferon gamma (IFNγ) and interleukin-17 (IL-17) were generalized features in patients with SLE. However, higher interleukin-10 (IL-10) levels were observed 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]. IFNγ was positively correlated with anti-double stranded DNA (anti-dsDNA) and anti-Sjogren's syndrome A (anti-Ro/SSA) [P = 0.0355 and p = 0.0402, respectively], while IL-17 was that with anti-Ro/SSA [P = 0.0130].

Conclusions: We demonstrated the crucial role of IFNβ as 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 mechanisms underlying LN to guide diagnosis and therapy.