Predominance of Type-2 Immune Response in Idiopathic Membranous Nephropathy

Abstract

Background: The Th1/Th2 paradigm is proving increasingly useful in the understanding of infectious diseases and many autoimmune diseases. Th1 cells predominantly produce interleukin-2 (IL-2) and interferon-γ (IFN-γ) and are instrumental in initiating delayed-type hypersensitivity and activating macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL-13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown that in patients with membranous nephropathy, there may be a predominance of Th2, because of the presence of IgG, particularly IgG4, which belongs to a subclass of the type-2 immune response, and complement deposits in glomeruli. In this study, we investigated the immunoresponse of helper T cells, i.e. Th predominance in patients with idiopathic membranous nephropathy. Methods: We used flow cytometry to assess the levels of circulating Th cells in patients with idiopathic membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the expression of intracellular type-1 and type-2 cytokines. Because the production of each of these cytokines has a specific time course, we observed the cytokine synthesis at 3, 6, 9 and 12 h after stimulation. Results: The percentages of IL-2+/CD4+ cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals at 6, 9 and 12 h, with the difference becoming more significant over time. IFN-γ+/CD4+ cells and IL-4+/CD4+ cells were not significantly different between the two groups. In patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+ cells were significantly higher than those in normal individuals at each point in time. Conclusion: Increased IL-10-producing Th cells may lead to suppression of delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis, resulting in idiopathic membranous nephropathy.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy

“…IL-10 plays an important role in renal physiology, as well as during acute kidney injury and progression to chronic renal failure. The degree of proteinuria correlates with progression of glomerulosclerosis and tubulointerstitial fibrosis, and IL-10 can promote the deposition of mesangial immune complexes, which contributes for the progression of glomerular injury [27][28][29][30].…”

Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1)

“…In addition to the correlation drawn between the predominance of Th2 responses and MGN pathogenesis in humans (32,46,47), there is considerable other evidence to suggest that the Th1/Th2 balance can affect disease outcome. Patients with chronic graft-vshost disease, a disorder in which the Th2 response is dominant, occasionally show MGN, but rarely DPGN (48 -50).…”

Correlation between B Lymphocyte Abnormality and Disease Activity in Patients with Idiopathic Membranous Nephropathy

“…7 Antibodies are secreted by plasma cells that are derived from B lymphocytes, implying that B lymphocytes play an important role in the pathogenesis of IMN. Experiments showed the type 2 helper (Th2) T-cells were the dominant cell type in patients with IMN 8 and that the cytokines secreted by Th2 cells could promote the production of immunoglobulin (Ig) G4 type antibodies by B lymphocytes, 9 resulting in membranous nephropathy.…”