Clinical Significance Of Soluble PD-1 And PD-L1 In Children With Primary Nephrotic Syndrome

Background and Objectives: Primary nephrotic syndrome(PNS)in children consists of physiological and pathological changes caused by unknown causes,in which increased glomerular filtration barrier permeability results in a large number of proteinuria.At present,the most common pathological type is minimal change disease without lymphocytic infiltration or immunoglobulin deposition in renal pathology.The characteristic change is podocyte fusion.Of course,other pathological types are also accompanied by changes in podocyte.From cell level,that are related to immune system disorders such as the disturbance of T and B lymphocytes;from molecular and genetic levels,that are related to abnormal expression of molecule associated podocyte slit diaphragm,causing glomerular filtration barrier damage and resulting in massive proteinuria.In recent years,many studies have been made about T,B lymphocytes and cytokines in blood and urine.Programmed death 1(PD-1)is a member of the CD28/CTLA-4 family.It is expressed in T cells,B cells,natural killer(NK)cells,monocytes,dendritic cells(DC)and so on.The binding of PD-1 and its ligand(programmed death ligand 1,PD-L1)can activate PD-1/PD-L1 signaling pathway,inhibit T cell activation,proliferation,differentiation and cytokine secretion,negatively regulates immune responses and improve immune tolerance.The PD-1 is involved in external pathogens immune response to protect the body from autoimmunity and cell killing physically,and have negative regulatory function in autoimmune diseases.The treatment of tumor with PD-1 antibody can cause the occurrence of nephrotic syndrome.The effect of PD-1/PD-L1 signaling pathway on PNS in children has not been reported.In this paper,the expression and clinical significance of soluble PD-1 and soluble PD-L1 in children with PNS were investigated.Methods: Serum and urine specimens from 37 children with primary nephroticsyndrome(including newly diagnosed and recurrent)admitted to the Department of Nephrology,Rheumatology and Immunology of Children’s Hospital of Soochow University from July 2017 to November 2017 were collected during the attack and remission period.The levels of s PD-1 and s PD-L1 in serum and urine were detected by enzyme-linked immunosorbent assay(ELISA),collecting data including the blood pressure,hematuria,peripheral blood lymphocyte subsets,biochemical indexes,humoral immunity,coagulation,24-hour urinary protein,urine protein profile and other clinical data during attack period group of children to analyze the interrelation among them.Results:(1)The level of s PD-1 in serum was lower in remission stage than those in healthy control group(P<0.01).The level of urinary s PD-1 in onset group was higher than that in remission and healthy control group(P<0.01).(2)The levels of s PD-L1 in serum were significantly higher in onset and remission stage than those in healthy control group(P<0.01).The levels of s PD-L1 in urine were higher in the seizure and remission group than those in the healthy control group(P<0.01).(3)The number of CD3 + T lymphocytes and CD3 + CD8 + T lymphocytes in peripheral blood of children with nephrotic syndrome did not change significantly.However,the counts of CD3 + CD4 + T lymphocyte,CD3-CD19 + and CD19 + CD23 + B lymphocyte and CD3-CD(16 + 56 +)NK cell were lower than those of the healthy control group,and the level of s PD-1 in the serum was correlated with the number of CD3 + T lymphocytes,CD3 +CD4 + T lymphocytes,CD3 + CD8 + T lymphocytes and CD3-CD19+ B lymphocytes,CD19 + CD23 + B lymphocytes positively(r>0,P<0.05).(4)The level of s PD-1 in the urine had positive relation with the ratio of 24 hours urinary albumin and weight(24U-MA/Wt),N-acetylglucosaminidase and urinary creatinine(UNAG/Cr)and β2 microglobulin and urinary creatinine(Uβ2MG / Cr)(r>0,P<0.05).Conclusions: The level of s PD-1 and s PD-L1 in serum and urine had obvious change during the onset and remission of children with primary nephrotic syndrome,which suggested that PD-1 / PD-L1 signaling pathway is involved in the development of childhood nephrotic syndrome.And it also associated with cellular immune imbalance from T & B lymphocyte level in accord with renal tubular injury.Further studies arerequired to investigate it’s detail effects on nephrotic syndrome and mechanisms underlying.