| Objective Henoch-Schonlein purpura (HSP) is a common vascular inflammatory disease in children. The pathological feature of HSP is systemic small vessels inflammatory damage that mediated by IgA. HSP mainly involve skin, joint, gastrointestinal tract and kidney, which characterized by nonthrombocytopenic purpura, arthrocele, arthralgia, abdominal pain, gastrointestinal bleeding, hematuria and albuminuria as clinical symptoms. Patients with HSP may present with some rare symptoms (e.g. peripheral or central nervous system involvement, pulmonary hemorrhage, orchitis, stenosing ureteritis). HSP with renal injury is named Henoch-Schonlein purpura nephritis (HSPN). Extrarenal injury of HSP is temporary, cannot cause long-term and chronic injury. Renal injury of HSP is chronic and persistent. The appearance and severity of HSPN are the key factor for long-term prognosis of children with HSP. Prediction of HSPN and effective monitoring of illness changes are very important for children with HSP to achieve good prognosis. The causes of HSP are manifold. HSP can be induced by infection, tumor, medicine and imbalance of autoimmunity. The pathogenesis of HSP has not been adequately understood until now, but the immunity is the key factor. Cytokines, adhesion molecules, inflammatory cells and complement actvation may play an important role in the pathogenesis of HSP. In addition, galactose-deficient IgAl (Gd-IgA1) has a specific role in the pathogenesis of HSPN, the processes of HSPN induced by Gd-IgA1include Gd-IgAl synthesis, deposition of Gd-IgA1immune complexes in glomeruli mesangial, complement activation, inflammatory cells infiltration and mesangial cells proliferation. Pentraxin3(PTX3) and C-reactive protein (CRP) belong to the pentraxins superfamily. PTX3is the prototypical peptide of long pentraxins, CRP is a member of short pentraxins. As the major acute-phase protein of human, CRP could be synthesized in the liver stimulated by a variety of inflammatory cytokines (mainly IL-6). Different from CRP, PTX3could be synthesized in a variety of peripheral tissues and cells (e.g. endothelial cells, macrophages, myeloid cells, smooth muscle cells, dendritic cells, synovial cells, cartilage cells, fat cells, alceolar epithelial cells, glial cells and fibroblasts) stimulated by various cytokines and endotoxins (e.g. IL-1, TNF, bacteria metabolic products), while IL-6cannot induce PTX3synthesis. Current clinical research found that PTX3played an important role in the pathophysiological process of various inflammatory diseases (e.g. cardiovascular system, respiratory system, digestive system, urinary system, connective tissue diseases, infectious diseases, poisoning). PTX3was a sensitive biomarker that can reflect the illness severity. As a biological indicator of inflammation stimulated by a variety of pro inflammatory signals, PTX3showed correlation with a number of immune related diseases. High expression of PTX3can be found in a number of immune related diseases, and PTX3levels showed close correlation with the conditions, complications and prognosis of diseases. In this study, we investigated the changes of plasma PTX3(pentraxin3) concentrations in children with HSP, explored the guiding function of the plasma PTX3concentration on the HSP condition and its effect on early prediction of the renal involvement in children with HSP.Methods A total of108cases consisting of71children with HSP and37NC (normal controls) children were enrolled in this study from March2010to February2013in Pediatric Department Qilu Hospital Shandong University.71children with HSP consisting of34children with HSP/no-nephritis (Henoch-Schonlein purpura without nephritis) and37chidlren with HSPN (Henoch-Schonlein purpura nephritis) were first diagnosed and hospitalized in our department. Plasma, serum and urine samples were collected from all objects of this study to measure the concentrations of blood urea nitrogen (BUN), serum creatinine, urine microalbumin (MALB), P2-microglobulin (β2-MG), plasma PTX3and plasma C-reactive protein (CRP). The24hours urine samples of children in HSPN group were collected to determine the24hours urinary protein quantity. Serum BUN and Cr concentrations were determined in the clinical biochemical laboratory, urine MALB and β2-MG in the central laboratory, plasma PTX3and CRP in the cryomedicine laboratory by enzyme-linked immunosorbent assay (ELISA),24hours urinary protein quantity in the emergency laboratory. IBM SPSS Statistics20.0software was used for statistical analysis. The x2test was used to analyze the categorical variables. The Kruskal-Wallis test, Wilcoxon test, T test and ANOVA were used to analyze the continuous variables on the basis of data conditions. Spearman’s correlation analysis was used to detect the relationship between the observed indexes. The receiver operating characteristic (ROC) curve analysis was used to compare and describe the PTX3and CRP in diagnosis value of disease. The area under the ROC curve (AUCROC) of1.0indicated the perfect diagnostic value, while AUCROC of0.5indicated no diagnostic value, AUCROC between0.5and0.7indicated low diagnostic value, AUCROC between0.7and0.9indicated good diagnostic value, AUCROC between0.9and1.0indicated better diagnostic value. The cut-off value, sensitivity, specificity and confidence interval (CI) were also described at the same time.Results1. The NC group included19boys (51.35%) and18girls (48.65%), the age of NC group was7.19±3.22years old. The HSP group included34boys (47.89%) and37girls (52.11%), the age of HSP group was6.88±2.44years old. There were no statistical differences in the age and gender between the two groups (p>0.05). The NC group included19boys (51.35%) and18girls (48.65%), the age of NC group was7.19±3.22years old. The HSP/no-nephritis group included16boys (47.06%) and18girls (52.94%), the age of HSP group was6.78±2.73years old. The HSPN group included18boys (48.65%) and19girls (51.35%), the age of HSP group was6.97±2.17years old. There were also no statistical differences in the age and gender between the three groups (p>0.05).2. There was no statistical differences in the serum BUN concentration between the NC and HSP group (3.18±1.09mmol/L vs.3.36±1.12mmol/L, p>0.05). There was no statistical differences in the serum Cr concentration between the NC and HSP group (25.14±10.48μmol/L vs.27.59±11.96μmol/L, p>0.05). There was also no statistical differences in the serum BUN concentration between the NC, HSP/no-nephritis and HSPN group (3.18±1.09mmol/L vs.3.09±0.88mmol/L vs.3.61±1.25mmol/L, p>0.05). There was also no statistical differences in the serum Cr concentration between the NC, HSP/no-nephritis and HSPN group (25.14±10.48μmol/L vs.26.68±11.75μmol/L vs.28.43±12.24μmol/L, p>0.05).3. Before treatment, the plasma PTX3concentration of HSP group was obviously higher than that of NC group (4.27(2.92,7.30)ng/ml vs.1.24(0.87,2.08)ng/ml, p<0.05), the plasma CRP concentration of HSP group was also obviously higher than that of NC group (5.55(3.49,8.02)mg/L vs.2.24(0.96,4.74)mg/L, p<0.05). After treatment, both of the plasma PTX3and CRP concentrations significantly decreased (4.27(2.92,7.30)ng/ml vs.1.27(0.92,2.19)ng/ml, p<0.05;5.55(3.49,8.02)mg/L vs.2.45(1.36,3.41)mg/L, p<0.05; respectively).Before treatment, the plasma PTX3concentration of HSPN group was obviously higher than that of HSP/no-nephritis and NC group (6.99(4.18,9.78)ng/ml vs.3.19(1.13,4.27)ng/ml, p<0.05;6.99(4.18,9.78)ng/ml vs.1.24(0.87,2.08)ng/ml, p<0.05; respectively). The plasma PTX3concentration of HSP/no-nephritis group was also obviously higher than that of NC group (3.19(1.13,4.27)ng/ml vs.1.24(0.87,2.08)ng/ml, p<0.05). The plasma CRP concentrations of HSP/no-nephritis and HSPN group were also obviously higher than that of NC group (5.16(3.84,8.27)mg/L vs.2.24(0.96,4.74)mg/L, p<0.05;5.67(3.43,8.07)mg/L vs.2.24(0.96,4.74)mg/L, p<0.05; respectively), there was no statistical difference in plasma CRP concentration between the HSP/no-nephritis and HSPN group (5.16(3.84,8.27)mg/L vs.5.67(3.43,8.07)mg/L, p>0.05). After treatment, the plasma PTX3and CRP concentrations of HSP/no-nephritis group significantly decreased (3.19(1.13,4.27)ng/ml vs.1.08(0.65,2.19)ng/ml, p<0.05;5.16(3.84,8.27)mg/L vs.2.52(1.38,4.02)mg/L, p<0.05; respectively). The plasma PTX3and CRP concentrations of HSPN group significantly decreased (6.99(4.18,9.78)ng/ml vs.1.29(1.01,2.26)ng/ml, p<0.05;5.67(3.43,8.07)mg/L vs.2.36(1.26,3.29)mg/L, p<0.05; respectively).4. The urine MALB concentration of HSP group was obviously higher than that of NC group (24.50(10.20,120.00)mg/L vs.8.30(6.05,11.00)mg/L, p<0.05). The urine β2-MG concentration of HSP group was also obviously higher than that of NC group (0.19(0.12,0.39)mg/L vs.0.11(0.07,0.14)mg/L, p<0.05).The urine MALB concentration of HSPN group was obviously higher than that of NC and HSP/no-nephritis group (108.00(56.10,1800.00)mg/L vs.8.30(6.05,11.00)mg/L, p<0.05;108.00(56.10,1800.00)mg/L vs.10.75(6.65,16.78)mg/L, p<0.05; respectively), there was no statistical difference in urine MALB concentration between the NC and HSP/no-nephritis group (8.30(6.05,11.00)mg/L vs.10.75(6.65,16.78)mg/L, p>0.05). The urine β2-MG concentration of HSPN group was obviously higher than that of NC and HSP/no-nephritis group (0.37(0.18,1.02)mg/L vs.0.11(0.07,0.14)mg/L, p<0.05;0.37(0.18,1.02)mg/L vs.0.14(0.10,0.19)mg/L, p<0.05; respectively), there was no statistical difference in urine β2-MG concentration between the NC and HSP/no-nephritis group (0.11(0.07,0.14)mg/L vs.0.14(0.10,0.19)mg/L,p>0.05).5. According to the24-h urinary protein quantity, the HSPN group was divided into three subgroups:Ⅰ,<150mg/d; Ⅱ,150mg/d-1000mg/d; Ⅲ,>1000mg/d. There was no statistical difference in serum BUN concentration between the three subgroups (3.71±0.89mmol/L vs.3.76±1.24mmol/L vs.3.37±1.65mmol/L, p>0.05). There was also no statistical difference in serum Cr concentration between the three subgroups (24.07±11.43μmol/L vs.29.18±9.97μmol/L vs.32.84±14.14μmol/L, p>0.05). The urine MALB concentration of the III group was obviously higher than that of I and II group (2195.00(1775.00,6087.50)mg/L vs.45.10(17.45,69.13)mg/L, p<0.05;2195.00(1775.00,6087.50)mg/L vs.120.00(82.00,180.00)mg/L, p<0.05; respectively), there was no statistical difference in urine MALB concentration between the Ⅰ and Ⅱ subgroup (45.10(17.45,69.13)mg/L vs.120.00(82.00,180.00)mg/L, p>0.05). The urine β2-MG concentration of the Ⅲ group was obviously higher than that of I and II group (1.55(1.00,2.65)mg/L vs.0.16(0.11,0.25)mg/L, p<0.05;1.55(1.00,2.65)mg/L vs.0.37(0.27,0.77)mg/L, p<0.05; respectively), there was no statistical difference in urine β2-MG concentration between the I and II subgroup (0.16(0.11,0.25)mg/L vs.0.37(0.27,0.77)mg/L, p>0.05). The plasma PTX3concentration of the III group was obviously higher than that of I and II group (9.98(8.41,15.74) ng/ml vs.4.32(2.86,6.72)ng/ml, p<0.05;9.98(8.41,15.74) ng/ml vs.4.96(4.16,9.42) ng/ml, p<0.05; respectively), there was no statistical difference in plasma PTX3concentration between the I and II subgroup (4.32(2.86,6.72)ng/ml vs.4.96(4.16,9.42) ng/ml, p>0.05). There was no statistical difference in plasma CRP concentration between the three subgroups (4.88(3.28,7.05)mg/L vs.4.15(2.28,8.36) mg/L vs.7.10(5.69,10.25) mg/L, p>0.05).6. Plasma PTX3concentration was positively correlated with plasma CRP concentration (p=0.532, p=0.001), urine MALB concentration (p=0.606, p<0.001), urine β2-MG concentration (p=0.490, p=0.002), and24-h urinary protein quantity (p=0.650, p<0.001), but no correlation with serum BUN concentration (p=-0.141, p=0.405) and serum Cr concentration (p=0.150, p=0.375). Plasma CRP concentration showed no correlation with serum BUN concentration (p=0.017, p=0.918), serum Cr concentration (p=-0.021, p=0.902), urine MALB concentration (p=0.293, p=0.078), urine β2-MG concentration (p=0.109, p=0.520) and24-h urinary protein quantity (p=0.315,p=0.058).7. The areas under the ROC curve (AUCROC) of the plasma PTX3was0.837(p<0.001),95%confidence interval (CI) was0.745～0.929. The optimal cutoff concentration of plasma PTX3was4.30ng/ml (sensitivity73.0%; specificity79.6%). The HSP children with the plasma PTX3concentration higher than4.30ng/ml may present HSPN. The AUCROC of CRP was0.514(p=0.845)(95%CI0.377～0.650), the plasma CRP concentration had no diagnostic function for the prediction of renal involvement in children with HSP.Conclusions1. PTX3could play an important role in multisystemic vasculitis of HSP, the plasma PTX3concentration obviously increased in children with HSP, especially in children with HSPN.2. PTX3participated in the development process of renal injury in children with HSP. Compared with plasma CRP, plasma PTX3can be used as a potential early biomarker to predict HSPN in children with HSP.3. Compared with plasma CRP, plasma PTX3concentration was positive correlated with the degree of renal injury in children with HSPN, can be used as an effective biological indicator to monitor the condition in children with HSPN. |
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