Anti-Cytokine Autoantibodies in Systemic Lupus Erythematosus

Abstract

Cytokine dysregulation is characteristic of systemic lupus erythematosus (SLE), a systemic autoimmune disease of considerable heterogeneity. Insights gained about the cytokine dysregulation in SLE have the potential for identifying patient subsets before the onset of clinical disease and during established disease. Clustering patients by cytokine and disease activity subsets is more informative than isolated cytokine studies, as both pro inflammatory and immunoregulatory cytokines contribute to the cytokine dysregulated state in SLE. Endogenous anti-cytokine autoantibodies (ACAAs) may be involved in the regulation of cytokine biology by reducing excessive production or by prolonging their half-life in the circulation through the formation of cytokine-antibody immune complexes. Although endogenous ACAAs may have deleterious effects such as contributing to immunodeficiency states, their role in the pathophysiology of autoimmune conditions such as SLE has yet to be clearly elucidated. The aim of the present article is to provide a focused review of the current knowledge of ACAAs in SLE.

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“… 67 Previous studies have found that approximately 25% of patients with SLE have anti-IFN antibodies. 73 , 74 , 75 , 76 , 77 The most common type I IFN autoantibodies in SLE are against IFN-α2 and IFN-ω, as seen in severe COVID-19. 77 In addition, some of these anti-IFN antibodies were shown to be effective at neutralizing type I IFN activity in vitro , and patients with neutralizing antibodies tended to have lower SLE disease activity.…”

Bacterial infections in lupus: Roles in promoting immune activation and in pathogenesis of the disease

“…The immune complexes formed can deposit in tissues and mediate antibody-dependent mechanisms of immune activation, such as complement activation, leading to inflammation and organ damage [ 10 ]. In addition, chronic activation of innate and adaptive immune cells results in a greatly altered cytokine milieu, with many cytokines found at increased levels [ [11] , [12] , [13] ].…”

Interleukin 4 deficiency limits the development of a lupus‐like disease in mice triggered by phospholipids in a non‐bilayer arrangement

“…19 Also, it is important to highlight that IL-4, and IL-5 as well as the chemokine interferon gamma inducible protein 10 have been found in patients more than three years before they satisfied SLE classification criteria. 21 In this study, we evaluated the participation of T H 2 cells through the role of IL-4, its hallmark cytokine, in the development of the murine lupus-like disease, by inducing the disease in IL-4 gene knockout BALB/c (IL-4 KO BALB/c) mice and in wild-type BALB/c mice. We found an important role for IL-4 in the development of this disease, since the IL-4 KO BALB/c mice only showed minor disease manifestations.…”