The interaction between circulating complement proteins and cutaneous microvascular endothelial cells in the development of childhood Henoch-Schönlein Purpura.

Yao-Hsu Yang,Chun-Jung Chang,Hui-Yao Hsu,I-Jung Tsai,Ya-Hui Chuang,Bor-Luen Chiang

doi:10.1371/journal.pone.0120411

Yao-Hsu Yang, Chun-Jung Chang + Show 4 more

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https://doi.org/10.1371/journal.pone.0120411

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Abstract

ObjectiveIn addition to IgA, the deposition of complement (C)3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP). The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP.MethodsPlasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow cytometry or by ELISA.ResultsAt the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001), C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001), and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 μg/ml, p < 0.0001), but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner.ConclusionIn HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels.

Highlights

Henoch-Schönlein purpura (HSP) primarily affects children with an annual incidence of 13– 20 cases per 100 000 < 17 years old children [1,2]
HSP patientderived acute phase plasma did not alter the presentation of C3a receptor (C3aR) and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5
In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels

Summary

Introduction

Henoch-Schönlein purpura (HSP) primarily affects children with an annual incidence of 13– 20 cases per 100 000 < 17 years old children [1,2]. It is a kind of leukocytoclastic vasculitis involving small vessels and clinically characterized by non-thrombocytopenic cutaneous palpable purpura, arthritis/arthralgia, bowel angina, gastrointestinal bleeding, and hematuria/proteinuria. Together with the deposition of IgA on small vessel wall and the infiltration of polymorphonuclear neutrophils (PMN) around the vessel and in the vessel walls, HSP is considered as an immune-mediated vasculitis possibly triggered by multiple environmental factors.

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