| Background:Retroperitoneal fibrosis(RPF)is a rare fibrous inflammatory disease in the retroperitoneal tissue characterized by inflammation and fibrosis of the soft tissues in the retroperitoneal and other abdominal organs.The disease may be immune-mediated,such as inflammatory cell infiltration with fibrotic response,and is associated with both autoimmune diseases and HLA-DRB 1*03.Idiopathic retroperitoneal fibrosis(IRPF),which accounts for about 70-80%of all RPFS,is a disease of unknown etiology with environmental and genetic predisposition,while secondary diseases are usually associated with malignancies,infections,drugs,radiation,or other diseases.It is generally believed that the pathogenesis of IRPF is related to different types of immune cells.The histological features of IRPF are a mixture of fibrous tissue and chronic inflammation.Fibrous tissue consists mainly of myofibroblasts in a type I collagen matrix.Inflammatory infiltrates consist of a large number of lymphocytes,plasma cells,and macrophages.Nodular aggregates with a B-cell core are surrounded by T cells(primarily CD4+T cells),reproducing the structure of the germinal center and revealing the formation of ectopic lymphocytes,which is typical of its findings.CD4+T cells are abundant in biopsy tissue.CD4+T cells are divided into unique subgroups based on the cytokines they secrete and their distinct functional capabilities:helper T cells 1(Th1),Th2,and Th17 have pro-inflammatory effects,causing autoimmunity and inflammation,while regulatory T cells(Treg)have anti-inflammatory effects,regulating immune balance,and maintaining immune tolerance.Although extensive and profound studies have been conducted on Thl and Th2 cells,a growing number of studies have found that Th17/Treg immune imbalance is involved in the pathogenesis of various autoimmune diseases.For IRPF,there are no studies on Th17/Treg immune balance.Therefore,the study of peripheral CD4+T cells in patients with IRPF helps to provide a new therapeutic strategy.Objective:1.To explore the characteristics of peripheral blood lymphocyte subsets in patients with IRPF;2.To explore whether Th17/Treg immune balance exists and whether it is related to the pathogenesis of IRPF;3.Explore the role of cytokines in the pathogenesis of IRPF.Methods:A total of 22 patients with IRFP admitted to the Rheumatology Department of the Second Hospital of Shanxi Medical University from December 2015 to October 2022(excluding those with definite diagnosis of IgG4-RD and elevated serum IgG4 level)were collected.There were 36 IgG4-RD(IgG4-RD-non-RPF)patients without RPF and 28 healthy controls(HC).History,laboratory data and imaging data of all patients were collected.The absolute number and percentage of peripheral blood lymphocyte subsets and CD4+T cell subsets in IRPF group,IgG4-RD-non-RPF group and healthy control group were detected by flow cytometry,and serum cytokine levels were detected by flow cytometry microbead array(CBA).The differences among peripheral blood lymphocyte subsets,CD4+T subsets and cytokines were compared among all groups.The correlation between Th17 cells and Treg cells and cytokines was analyzed,and the working characteristics of subjects were used to predict the related factors of disease progression.Results:1.Compared with the healthy group,the absolute value of peripheral blood B cells in IRPF patients decreased significantly,and there were no obvious abnormalities in T,NK,CD4+T and CD8+T.The absolute number of Thl and Th2 cells was lower than that of the healthy group(85.78(55.58-135.96)vs.141.75(82.73-159.18),p=0.118,4.88(2.87-7.68)vs.8.27(4.93-10.66),p=0.043).The absolute number of Treg cells was significantly lower than that of healthy group(19.55(12.18-30.16)vs.34.55(28.20-46.38),p<0.001),while the absolute number of Th17 cells increased(p=0.682).Th17/Treg was significantly higher than that in healthy group(0.32(0.24-0.47)vs.0.16(0.09-0.23),p<0.001).2.Compared with IgG4-RD-non-RPF group,the absolute values of T(P=0.036),CD4+T(P=0.011),Th1(P=0.001)and Th2(P=0.004)in IRPF group were significantly decreased,but there was no significant difference in the absolute values of Th17 cells,Treg cells and Th17/Treg cells.3.Cytokine analysis showed that the level of IL-4 in IRPF patients was higher than that in healthy group(p=0.011),IL-6(p<0.001),IL-10(p<0.001),IL-17(p<0.001),TNF-α(p<0.001)and IFN-γ(p<0.001)were significantly higher than the healthy group,but no significant difference was found in IL-2.4.The absolute value of Treg cells and EOS in IRPF patients(r=0.747,p<0.001)was positively correlated with TG-Ab(r=-0.546,p=0.023).Th17 cells,Treg cells and Th17/Treg ratio were not significantly correlated with levels of IL-2,IL-4,IL-6,IL-10,IL-17,IFN-γ,and TNF-α(p>0.05).5.IL-10 and TNF-α predicted the subjects areas under the working characteristic curves of bilateral ureteral dilatation in IRPF patients were 0.813(95%CI:0.607-1.000,p=0.026)and 0.950(95%CI:0.856-1.000,p=0.001),respectively.IL-6 predicted bilateral ureteral obstruction with subject area under the working characteristic curve of 0.861(95%CI:0.682-1.000,p=0.015).Conclusion:Peripheral blood Treg cells decreased in patients with IRPF,and Th17/Treg immune imbalance was indeed present,which was associated with disease pathogenesis and may be a potential target for treatment of IRPF.The levels of IL-6,IL-10 and TNF-α seem to be related to the progression of IRPF,providing a new strategy for immunoregulatory therapy. |
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