| Background: Henoch-Schonlein purpura (HSP) is the commonest vasculitis in children. The clinical features are characterized mainly by nonthrombocytopenic purpura, arthritis or arthralgia, abdominal pain, gastrointestinal bleeding and nephritis. The majority of the scholars believed that HSP was a kind of systemic vasculitis mediated by autoimmune responses, though it's exact etiological factors and pathogenesis remained indistinct. Recent researches have indicated that a number of receptor-ligand molecules of costimulators took part in the pathologic processes of many autoimmune diseases in different ways and stages of the immune responses. So, it could provide new therapeutic targets against HSP by studies of the expression features and biological significance of PD-1, OX40 molecules in child with HSP.Objective: To explore the expressions and significance of costimulatory molecules PD-1, OX40 in peripheral blood of HSP patients.Methods: 25 children with HSP who were hospitalized for the first time were selected from children's hospital affiliated to Soochow University as the experimental group (6 for dermatic type, 6 articular type, 5 abdominal type, 3 nephritic type and 5 mixed type) in contrast to 17 healthy children. The fresh peripheral blood mononuclear cells (PBMC) from vein were isolated by density gradient centrifugation. Then FCM and ELISA were proceeded to determin the expressions of PD-1, OX40/OX40L on PBMC and sPD-1, sOX40L in serum respectively. Their relationships with subtypes of HSP and early renal injury were analyzed.Results: (1)The expression of PD-1 on PBMC in children with HSP was remarkably higher than the control group (7.73±3.64% V.S 3.28±2.12%, P<0.01), especially in mixed type and nephritic type group. (2)The sPD-1 level in serum of children with HSP was significantly higher than the control group (54.47±25.68 V.S 21.89±11.66ng/ml, P<0.01). (3)The expressions of OX40 and OX40L on T lymphocyte cells of the patients were 14.74±9.56% and 17.18±12.25% respectively, higher than control group (both P <0.01). There were higher expressions of this two molecules in Nephritic type and mixed type group than in dermatic type group, which showed its correlation with their severity. (4) The sOX40L level had a positive correlation with beta-2-microglobulin and urine microalbumin/creatinine ratio (r=0.60, P<0.01;r=0.59, P<0.01 respectively ). (5)The expressions of PD-1, sPD-1 level in children with HSP were markedly correlated to serum IgA (r=0.74 P<0.01; r=0.69 P<0.01 respectively);10 cases with >30mg/g of urine microalbumin/creatinine ratio had higher PD-1 and sPD-1 than the other 15 <30mg/g group; Furthermore, PD-1 and sPD-1 both had positive correlations with urine microalbumin/creatinine ratio (r=0.56 P<0.01; r =60 P<0.01 respectively). (6)18 children with higher level of beta-2-microglobulin had more PD-1 expression,sPD-1 level than the other 7children with normal urine beta-2-microglobulin; Also, PD-1,sPD-1 had positive correlations with urine beta-2-microglobulin (r=0.60 P<0.01;r=0.54 P<0.01 respectively).Conclusions: The abnormal high expressions of costimulatory molecules PD-1,OX40/OX40L on PBMC in children with HSP demonstrated that PD-1/PD-1L and OX40/OX40L may be involved in the process of HSP. To activate the negative signal and block the positive signal of costimulatory molecules could possibly provide new ways to treat HSP patients. The expressions of PD-1,sPD-1 and sOX40L level had positive correlations with urine microalbumin/creatinine ratio and beta-2-microglobulin. These indicated that PD-1,sPD-1 and sOX40L can possibly be used as immunologic marks to monitor the severity and discover early renal injury in children with HSP.
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