Th2 Cytokines Increase and Stimulate B Cells to Produce IgG4 in Idiopathic Membranous Nephropathy

Background: The predominant deposition of IgG4 in idiopathic membranous nephropathy indicates that its presence characterizes the systemic immune response of the disease.

Methods: We analyzed the expressions of CD3, CD19, CD4, and CD8 on peripheral blood mononuclear cells (PBMCs) by flow cytometry, and the levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interferon (IFN)-gamma, interleukin (IL)-4, IL-10, and IL-13 mRNAs in PBMCs using real-time reverse transcription-polymerase chain reaction (RT-PCR) in 14 patients with idiopathic membranous nephropathy and 14 normal control donors. The levels of IgG subclasses in the B-cell culture supernatant in the presence or absence of cytokines were quantified by enzyme-linked immunosorbent assay (ELISA).

Results: Idiopathic membranous nephropathy patients showed an increased CD4(+)/CD8(+) ratio, although the numbers of peripheral T and B cells were comparable to those of the normal control group. IL-10 and IL-13 mRNA expression levels increased in the idiopathic membranous nephropathy group. The levels of spontaneous production of each IgG subclass by B cells were identical in the two groups. In the presence of Th2 cytokines, B cells from several individuals of the idiopathic membranous nephropathy group augmented the production of IgG4. When the individual levels of each IgG subclass in the presence of cytokines were compared with those in the absence of cytokines in each sample, a significant increase in the production of IgG4 in the presence of IL-4 was observed in the idiopathic membranous nephropathy group.

Conclusion: These results indicate that the altered functions of T cells to produce Th2 cytokines and the increased production of IgG4 by B cells in response to these cytokines characterize the immune response in idiopathic membranous nephropathy.