Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schonlein purpura) nephritis



Wright, Rachael D ORCID: 0000-0002-7606-2297, Marro, Julien ORCID: 0000-0003-4954-7915, Northey, Sarah J, Corkhill, Rachel, Beresford, Michael W and Oni, Louise ORCID: 0000-0002-1532-2390
(2023) Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schonlein purpura) nephritis. PEDIATRIC NEPHROLOGY, 38 (5). pp. 1491-1498.

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Abstract

<h4>Background</h4>Children with immunoglobulin A vasculitis (IgAV Henoch-Schönlein purpura) frequently encounter nephritis (IgAV-N) with 1-2% risk of kidney failure. The pathophysiology of IgAV-N is not fully understood with speculation that complement may contribute. The aim of this study was to identify whether urinary complement proteins are increased in children with IgAV-N.<h4>Methods</h4>A cross-sectional prospective cohort of children with IgAV were recruited together with controls including healthy children and children with systemic lupus erythematosus (SLE). Patients were subdivided according to the presence of nephritis. Urinary C3, C4, C5, and C5a were measured by enzyme-linked immunosorbent assay (ELISA) and corrected for urinary creatinine.<h4>Results</h4>The study included 103 children; 47 with IgAV (37 IgAV without nephritis, IgAVwoN; 10 IgAV-N), 30 SLE and 26 healthy children. Urinary complement C3, C4, and C5 were all statistically significantly increased in all children with IgAV compared to SLE patients (all p < 0.05). In patients with IgAV-N, urinary complement C3, C4, C5, C5a were all statistically significantly increased compared to IgAVwoN (C3 14.65 μg/mmol [2.26-20.21] vs. 2.26 μg/mmol [0.15-3.14], p = 0.007; C4 6.52 μg/mmol [1.30-9.72] vs. 1.37 μg/mmol [0.38-2.43], p = 0.04; C5 1.36 μg/mmol [0.65-2.85] vs. 0.38 μg/mmol [0.03-0.72], p = 0.005; C5a 101.9 ng/mmol [15.36-230.0] vs. 18.33 ng/mmol [4.27-33.30], p = 0.01). Using logistic regression, the urinary complement components produced an outstanding ability to discriminate between patients with and without nephritis in IgAV (AUC 0.92, p < 0.001).<h4>Conclusions</h4>Children with IgAV-N have evidence of increased complement proteins present in their urine that may indicate a pathological role and may allow treatment stratification. A higher resolution version of the Graphical abstract is available as Supplementary information.

Item Type: Article
Uncontrolled Keywords: Nephritis, Vasculitis, Immunoglobulin A, Complement, Biomarker, Urine
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 03 Nov 2022 10:08
Last Modified: 26 Apr 2023 04:23
DOI: 10.1007/s00467-022-05747-3
Open Access URL: https://doi.org/10.1007/s00467-022-05747-3
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165959