The pathogenesis of CD4⁺ T lymphocytes in IgA nephropathy

Objective To study the pathogenesis of CD4⁺ T lymphocytes in IgA nephropathy (IgAN). Methods A total of 45 cases of IgA nephropathy,hospitalized and diagnosed by first renal biopsy in Department of Nephropathy, Minhang Branch Hospital affiliated to Fudan University, were selected as the IgAN group (45cases). Another 49 healthy physical persons who examined in our medical center were selected as the normal control group (49 cases). The peripheral blood samples of the patients in the two groups before and after treatment were collected, to isolate peripheral blood lymphocytes, monocytes and serum.ELISA method was adopted to detect CD4⁺ T lymphocyte factor including interferon-γ (IFN-γ), interleukin 4(IL-4), IL-17, IL-21 and transforming growth factor-β1 (TGF-β1).The distribution proportion of CD4⁺ T cells was detected by flow cytometry.Meanwhile, the expression level of JAK/STAT signal pathway was detected by RT-qPCR and Western blot. Results The levels of serum IL-4, IL-17, TGF-β1 and IL-21 in the IgAN group were higher than those in the normal control group (P<0.05); the IFN-γ level had no statistical significant difference from that in the normal control group (P>0.05). After treatment for 1 month with hormone, the levels of serum IL-4, IL-17, TGF-β1and IL-21 in the IgAN group were all significantly lower than those before treatment (P<0.01). Compared with the normal control group, the proportions of Th2 and Treg cells before treatment in the IgAN group were increased significantly were increased significantly(P<0.05), but the proportion of Th1 had no statistically significant difference between the two groups(P>0.05). RT-qPCR and Western blot results showed, the expression levels of JAK1, JAK3, STAT3 and STAT6 before treatment in the IgAN group were significantly higher than those in the normal control group(P<0.05); while the STAT5 expression level was significantly lower than that in the normal control group(P<0.05). And, there was no significant difference in the expressions levels of JAK2, Tyk2, STAT1 and STAT4 between the two groups(P>0.05). Conclusions The imbalance of CD4⁺ T cell subsets may be involved in the pathogenesis of IgAN and may be related to the expression imbalance of JAK/STAT signaling pathway. Therefore, CD4⁺ T cytokines (IL-4,IL-17,TGF-β1 and IL-21) may be a new target for the treatment of IgAN and a non-invasive biomarker for monitoring the condition of IgAN.