| Aim: To study the expression of circulating Tfh cells and subsets, also evaluating their correlation with the clinical indexes such as e GFR and urine protein in adult MCD patients, to further explore the probably role of immune cells such as Tfh cells in the immunity response.Methods: We examined 27 patients with MCD and 14 matched control subjets(CS) of the levels of serum IL-21 by Enzyme-linked immunosorbent assay(ELISA)and the frequency of circulating programmed death-1(PD-1)+, inducible T cell costimulator(ICOS)+, IL-21+ Tfh cells, Ig D+, CD27+, CD86+, CD95+ B by flow cytometry analysis. The numbers of leukocytes and lymphocytes and serum concentrations of triglycerides, cholesterol, uric acid, and albumin were determined using ADVIA 2400 biochemical analyzer; In addition, urinary protein concentration and e GFR levels were determined. The serum concentrations of IFN-γ, TNF-α, IL-2,IL-4, IL-10, IL-6, IL-17 A were determined by CBA(Cytometric Bead Array, CBA).Results: 1. The frequency of circulating CD4+CXCR5+ Tfh, ICOS+ Tfh, PD-1+Tfh, IL-21+ Tfh cells were significantly greater(P<0.05). 2. An increased levels of serum IL-17 A, IFN-γ, IL-10, IL-4, IL-2 and IL-21 were found in the MCD patients(P<0.05). 3.The values of e GFR are negatively associated with the frequency of CD4+CXCR5+ Tfh cells(P=0.0104, R=0.4849), the concentrations of 24 h urinary proteins and serum IL-21 are positively associated with the frequency of PD-1+ Tfh(P=0.0141, R=0.4667; P=0.0007, R=0.6137), the concentrations of 24 h urinary proteins and serum IL-21 are positively associated with the frequency of ICOS+ Tfh(P<0.0001, R=0.7519; P=0.006, R=0.6201), the levels of serum Ig G, Ig M arepositively associated with the levels of serum IL-21(P=0.0255, R=0.4291; P=0.0005,R=0.6234), the frequency of ICOS+Tfh are positively associated with the levels of serum Ig G(P=0.0038, R=0.5375), the percentages of PD-1+Tfh cells are positively associated with the levels of serum Ig M(P=0.0077, R=0.5012), and the levels of serum Ig M, Ig G are positively associated with the frequency of CD19+B cells(P=0.0078, R=0.5008; P=0.0018, R=0.4394). 4. Post-treatment the circulating CD4+CXCR5+(P=0.0356), PD-1+(P=0.0127), ICOS+(P=0.0059) Tfh cell were significantly reduced. The level of serum IL-10(P=0.0009), IL-4(P=0.0333) were significantly increased. The levels of serum IL-21(P=0.0003) were significantly reduced. 5. Post-PDN treatment the circulating CD4+CXCR5+(P=0.0417), PD-1+(P=0.0337), ICOS+(P=0.0403) Tfh cell were significantly reduced. The level of serum IL-10(P=0.0145), IL-4(P=0.0003) were significantly increased. The levels ofserum IL-21(P=0.0083) were significantly reduced. 6. The frequency of circulating Ig D+CD27-B, CD86+B, CD95+B cell were significantly greater(P<0.05).The frequency of circulating Ig D+CD27+B cell were significantly reduced(P<0.05).Besides, the frequency of circulating CD4+CXCR5+Tfh are positively associated with the frequency of CD19+B cells(P<0.001, R=0.8631), the frequency of circulating PD-1+CXCR5+Tfh are positively associated with the frequency of CD95+B cells(P=0.0167, R=0.4565), the frequency of circulating ICOS+CXCR5+Tfh are negatively associated with the frequency of CD95+B cells(P=0.0041, R=0.5341).Conclusions: 1. Abnormal activation of circulating Tfh cells through the molecules: ICOS, PD-1, and the secretion of IL-21 to regulate humoral responses,which can produce auto antibodies and demage kidney function, indicate that peripheral blood ICOS+Tfh, PD-1+Tfh cells may be associated with the development of MCD. 2. B cell surface molecule CD86 or Ig D stimulate B cells activation, induce the humoral immune, secrete immunoglobulin may leads to the pathogenic process of MCD. 3. Circulating Tfh cells and B cells may participate as an intervention for the early treatment of MCD patients, which may provides a newway for clinical practice. |
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