Immunoregulatory defects in patients with systemic lupus erythematosus in clinical remission

Abstract

Little is known about the immune system of patients with systemic lupus erythematosus (SLE) during periods of silent disease. To address this issue we analysed lymphoid populations andcytokine production of mononuclear cells obtained from SLE patients in remission. We studied 43 patients with inactive disease, 10 with active disease and 30 controls. Remission was defined as at least 1 year during which lack of clinical disease activity permitted withdrawal of all treatment. Remission length ranged from 1 to 30 years. Flow cytometry and ELISA were used to study lymphoid populations (CD4, CD8 and CD19) and cytokine production (IL-2, 4, 10, 12 and 18). Patients with short remission periods (up to 15 years) exhibited an increased percentage of B cells; production of IL-2, IL-10 and IL-12 was decreased; production of IL-18 was increased. Interestingly, patients from groups with long time of inactive disease had corrected most alterations, but had an impaired IL-18 expression. IL-12 production correlated strongly with the length of the remission period (r = 0.7565). The immune system of patients with inactive lupus has partially corrected the disturbances present during disease activity. This is accomplished gradually, sometimes until counter-regulatory alterations are developed. This may allow patients to remain without disease activity.

N‐Ras or K‐Ras inhibition increases the number and enhances the function of Foxp3 regulatory T cells

“…Disease activity in various autoimmune disorders is indeed found to be associated with defective suppressive properties [3,5]. We showed here that the suppressive effect of Treg from mice treated with the Ras inhibitor is more robust than that from untreated controls.…”

“…Patients with various autoimmune disorders possess naturally occurring CD4 + CD25 + Treg that have diminished functional properties and whose numbers in the circulation are relatively small [3][4][5]. These observations are corroborated by findings of essentially similar defects in Treg cell homeostasis in animal studies of experimental immune-mediated disorders [3][4][5].…”

HDAC Inhibition in Lupus Models

“…Within the Th subpopulation, there also is an imbalance between Th1 and Th2 cytokine production in SLE (81)(82)(83). Activated Th2 cells overproduce IL-6, IL-12, IL-10 and tumor necrosis-α, whereas Th1 cells under produce IL-2, IFN-γ and transforming growth factor-β (TGF-β) (84)(85)(86).…”

Retinal Self-Antigen Induces a Predominantly Th1 Effector Response in Axl and Mertk Double-Knockout Mice

“…The Treg CD4 T cell subset expresses CD25 on the cell surface and the intracellular transcription factor Foxp3 (14, 15) and acts as an inhibitory cell type by releasing inhibitory cytokines, e.g., IL-10 and tumor growth factor (TGF)-β, and plays a critical role in T-cell-dependent peripheral tolerance (16–19). Developmental or functional anomalies, or alteration in the number, of Treg cells have been linked to several chronic inflammatory and autoimmune diseases, such as multiple sclerosis (20), rheumatoid arthritis (21), and systemic lupus erythematosus (22). …”