Expression And Related Clinical Significance Of PD-1+Tfh Cell Subsets In Adult Patients With Minimal Change Disease

Objective:In particular,programmed cell death protein 1(PD-1)+ Tfh cells,as a unique cell subgroup in T follicular helper cells(Tfh),play a fundamental role in the normal immune response.The purpose of this study was to determine the changed frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease(MCD)Methods:Flow cytometry analysis was used to measure the frequency of circulating PD-1+CXCR5+ T cell subsets and CD19+ B cells in 18 patients with MCD and 10 healthy controls(HCs).Glomerular filtration rate(e GFR)was calculated according to clinical indicators.24-hour urinary protein was quantified by automatic biochemical analyzer..Serum cytokine concentration was measured by enzyme-linked immunosorbent assay(ELISA)and cytometic bead array(CBA).Potential associations among the values of different measures were analyzed by the Sperman correlation test.Results:1:The frequencies of circulating PD-1+,PD-1+CD154+,and PD-1+IL-21+ Tfh cells were significantly increased in the peripheral blood of MCD patients compared with the healthy controls(HCs)(P < 0.05).However,no significant difference was found in PD-1+BCL-6+ or PD-1+ICOS+ Tfh cells.2:The frequencies of CD38 + CD19+and CD40 + CD38 + CD19 + B cells in the peripheral blood of MCD patients was significantly higher than that of healthy controls(P < 0.05).3: The plasma levels of IL-2,IL-4,IL-17 A,IL-6,IL-21 and interferon(IFN)-? in the MCD patients were significantly increased(P < 0.05).4: the frequencies of PD-1+ Tfh andPD-1+CD154+ Tfh cells were negatively correlated with the estimated glomerular filtration rate(e GFR),but positively correlated with the 24-h urinary protein concentration and serum IL-21 level.The frequencies of PD-1+ Tfh and PD-1+CD154+ Tfh cells were positively correlated with the frequencies of CD38+plasma cells and active CD38+CD40+ plasma cells,respectively.5:After an 8-12 week treatment with prednisolone,the frequencies of PD-1+,PD-1+CD154+,and PD-1+IL-21+ Tfh cells as well as the serum level of IL-21 were significantly reduced;Nevertheless,increased serum IL-4 and IL-10 level(P < 0.05)is detected..Conclusion:1: PD-1+Tfh and PD-1+CD154+Tfh cells may regulate the maturation and differentiation of B cells through the release of cytokines and the binding of ligand molecules,and participate in the pathogenesis of MCD by stimulating plasma cells to produce large amounts of immunoglobulin.2: The decreased frequency of activated PD-1 + Tfh cells in peripheral blood of MCD patients after treatment demonstrates once again that abnormal expression of PD-1+ T follicular helper cells may be involved in the pathogenesis of minimal change diseases.3: By comparing the clinical correlation indices,we found that PD-1+CD154+Tfh cells show a most important functional role in contrast to other subset of PD-1+T follicular helper cells in the pathogenesis of minimal change diseases.