Elevated interleukin-25 and its association to Th2 cytokines in systemic lupus erythematosus with lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is associated with lupus nephritis, initiated by the deposition of immune complexes in the kidney; subsequently, this induces the overexpression of cytokines. Lupus nephritis is known as one of the major clinical manifestations that affect the disease severity in SLE patients. An increased number of resident periglomerular and immune cells in the kidney has the potential to affect the equilibrium of different immune cell subsets, such as Th1, Th2, Th17, and Tregs, which may be central to the induction of tissue damage in kidney by exerting either proinflammatory or anti-inflammatory effects, or both. This equilibrium has yet to be confirmed, as new players such as IL-25 remain undiscovered. IL-25 is a cytokine of the IL-17 family, which stimulates Th2-mediated immune response when overly expressed. Thus, the aim of this research is to determine the plasma levels of IL-25 and Th2-associated cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) in SLE patients with (SLE-LN) and without lupus nephritis. Sixty-four (n = 64) SLE patients and fifteen (n = 15) healthy individuals were recruited. This study demonstrated that the IL-9, IL-10 and IL-25 had significantly increased expressions in SLE-LN, followed by SLE without LN, compared to healthy controls. Meanwhile, IL-5 and IL-6 had significantly reduced. No significant difference was observed with IL-13, while the level of IL-4 was undetectable. Furthermore, IL-9 and IL-10 were significantly correlated with the IL-25, and IL-25, IL-9 and IL-10 were positively correlated with the disease severity score, SLEDAI. In conclusion, IL-25 and its associated Th2 cytokines (IL-9 and IL-10) may be involved in SLE pathogenesis. These cytokines could be potential biomarkers in monitoring and predicting the disease severity during SLE pathogenesis.

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

“…A total of 100 Malaysian Malay female patients diagnosed with SLE between January 2016 and October 2017 were included in this cohort study. The demographic and clinical and laboratory findings which were significant and relevant to this SLE study cohort are depicted in Table 1 [part of the data of this SLE study cohort was published ( 38 )]. Among the 100 SLE patients, 70 patients (mean age 31.03 ± 0.95 years) were diagnosed without LN while 30 SLE patients (mean age 29.60 ± 1.23 years) were diagnosed with LN, as confirmed by a nephrologist in Hospital Serdang, Malaysia, by renal biopsy.…”

“…The main clinical manifestations presented in SLE patients with and without LN are shown in Figure 1 [part of the data of this SLE study cohort was published ( 38 )]. In general, Malay SLE patients without LN were likely presented with milder clinical complications, while Malay SLE patients with LN were more vulnerable to severe clinical manifestations.…”

Evaluation of the Effects of 1,25VitD3 on Inflammatory Responses and IL-25 Expression

“…IL-25 plays an anti-inflammatory role in Th1 and Th17 related disorders, including autoimmune diseases ( Selvaraja et al, 2019 Fallon et al, 2006 ). Similar to the URSA, inflammatory responses of Th17 cells play a key role in the immunopathogenesis of autoimmune disorders such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and autoimmune encephalomyelitis.…”

Roles of IL-25 in Type 2 Inflammation and Autoimmune Pathogenesis

“…Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease involving multiple organs including kidney and brain, characterized by anti-nuclear autoantibody (ANA) and immune complex deposition in kidney, which further causes immunecomplex glomerulonephritis (87,88). Several studies show that IL-25, together with other Th2-related cytokines, is significantly increased in SLE patients, especially in those with lupus nephritis, contributing to the pathogenesis of SLE (89,90).…”