Proteome analysis reveals novel serum biomarkers for Henoch-Schönlein purpura in Chinese children

Abstract

Purpose: Henoch-Schönlein purpura (HSP) is diagnosed based on characteristic skin changes. This study aimed to identify the serum biomarkers of HSP in children.

Experimental design: We performed proteomic analysis of serum samples from 38 paired pre- and posttherapy HSP patients and 22 healthy controls using a combination of magnetic bead-based weak cation exchange and MALDI-TOF MS. ClinProTools was used to screen the differential peaks. Then, LC-ESI-MS/MS was performed to identify the proteins. ELISA was used to verify the expression of whole protein in the serum of 92 HSP patients, 14 peptic ulcer disease (PUD) patients and 38 healthy controls, which were prospectively collected. Finally, logistic regression analysis was performed to analyze the diagnostic value of the above predictors and existing clinical indicators.

Results: Seven potential HSP serum biomarker peaks (m/z:1228.95, m/z:1781.22, m/z:1468.43, m/z:1619.53, m/z:1868.41, m/z:1694.05, m/z:1743.25) with higher expression in the pretherapy group and one peak (m/z:1947.41) with lower expression in the pretherapy group were all identified as peptide regions of albumin (ALB), complement C4-A precursor (C4A), tubulin beta chain (TUBB), isoform 1 of fibrinogen alpha chain (FGA), and ezrin (EZR). The expression of identified proteins was validated by ELISA. Multivariate logistic regression analysis showed that serum C4A EZR and ALB were independent risk factors for HSP, serum C4A and lgA were independent risk factors for HSPN, and serum D-dimer was an independent risk factor for abdominal HSP.

Conclusions and clinical relevance: These findings revealed the specific etiology of HSP from the perspective of serum proteomics. The identified proteins might serve as potential biomarkers for HSP and HSPN diagnoses.

Significance: Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and its diagnosis depends primarily on characteristic skin changes. Early diagnosis of non-rash patients is difficult, especially for abdominal and renal types (Henoch-Schönlein purpura nephritis, HSPN). HSPN has poor outcomes, is diagnosed based on urinary protein and/or haematuria, and cannot be detected early in HSP. Patients with an earlier diagnosis of HSPN appear to have better renal outcomes. Our plasma proteomic analysis of HSP in children revealed that HSP patients could be distinguished from healthy controls and peptic ulcer disease patients using complement C4-A precursor (C4A), ezrin, and albumin. C4A and IgA could distinguish HSPN from HSP in the early stages, and D-dimer was a sensitive index used to distinguish abdominal HSP; identifying these biomarkers could promote the early diagnosis of HSP, especially pediatric HSPN and abdominal HSP, thereby improving precision therapy.

Keywords: Early diagnosis; Henoch-Schönlein purpura; Mass spectrometry; Serum biomarker.