Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis

Abstract

IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

“…Previously, He et al have reported that the Wnt signaling pathway may be involved in the modulation of HSPN pathogenesis [10]. In this study, this pathway was found to be active during the progression of HSPN from type 2 to type 3 ( Supplementary Table S5), a period when renal injury can be relatively serious.…”

“…Recently, there have been several HSP-related researches using genome-wide methods, including a thorough review published in Autoimmunity Reviews summarizing the genetic component associated with the pathogenesis of HSP [9]. Researchers in China have reported on the proteomic alterations between HSP and HSPN patients in the Chinese population using comparative proteomic analysis [10]. Additionally, we previously published a study that revealed three potential biomarkers associated with the progression of HSP to HSPN [11].…”

“…BioMed Research International enrichment results, and those functions were related to nephritis and renal injury [10,15,19]. It is worth noting that most proteins were differentially expressed between different types of HSPN while their corresponding mRNAs were not differentially expressed between those groups (Supplementary Table S2 and Supplementary Table S3).…”

Urinary proteomics of Henoch-Schönlein purpura nephritis in children using liquid chromatography-tandem mass spectrometry

“…However, proteomic analysis of HSPN has rarely been studied, especially in urine. He XL et al performed a comparative analysis of serum proteomes by LC-MS/MS that revealed proteomic alterations in HSPN patients [19]. An analysis of urinary polypeptides from HSPN patients by electrophoretic methods detected urine proteins such as collagen alpha-1 (I) and (III) and alpha-1-antitrypsin [20].…”

Hospitalisation rates and characteristics for adult and childhood immunoglobulin A vasculitis in Western Australia

“…Immunoglobulin A vasculitis (IgAV), formerly Henoch–Schönlein purpura (HSP), is a type of systemic small vessel vasculitis characterised by transmural vessel wall inflammation with leukocyte disintegration accompanied and probably triggered by IgA depositions . Respiratory infections are considered a key trigger for the generation and deposition of IgA immune complexes with increased IgAV frequency reported during colder months .…”