Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

“…We also found that 20.9% of the variance in the SLEDAI score was predicted by the Th1+Th17/Th2 ratio, increased IL‐10 and BMI (all positive) and the proinflammatory profile (negative) association. These findings are in line with recent studies reporting dysregulated Th1, Th2 and Th17 balances in SLE, with responses skewing towards Th17 and with higher Th1/Th2 and Th17/Th2 ratios 32 , 33 , 34 . This disruption is related to increased disease activity and organ damage 32 , 33 .…”

“…These findings are in line with recent studies reporting dysregulated Th1, Th2 and Th17 balances in SLE, with responses skewing towards Th17 and with higher Th1/Th2 and Th17/Th2 ratios 32 , 33 , 34 . This disruption is related to increased disease activity and organ damage 32 , 33 . Furthermore, visceral fat contributes to systemic immune activation and inflammation and this condition is a promoter of oxidative stress, 35 which all together are associated with disease progression.…”

“…[32][33][34] This disruption is related to increased disease activity and organ damage. 32,33 Furthermore, visceral fat contributes to systemic immune activation and inflammation and this condition is a promoter of oxidative stress, 35 which all together are associated with disease progression. The negative associations between SLEDAI and proinflammatory cytokines need further discussion.…”

Increased ratio of Th17 cells to SIGIRR+CD4+ T�cells in peripheral blood of patients with SLE is associated with disease activity

“…It has been suggested that the inappropriate regulation of Th17 cells may be a key event in the pathogenesis of rheumatoid arthritis and SLE (22). A number of studies have reported significantly higher serum levels of IL-17 and a higher frequency of IL-17-producing PBMCs in patients with SLE compared with normal individuals (6,7,13).…”

“…Th17 cells, producing IL-17 amongst other cytokines, have been demonstrated to serve a critical role in the pathogenesis of SLE (10)(11)(12). Th17 cells and multiple cytokines are involved in autoimmune diseases including SLE and LN (13).…”