Early decreased plasma levels of factor B and C5a are important biomarkers in children with Kawasaki disease

Abstract

Background:The mechanisms underpinning Kawasaki disease (KD) are incompletely understood. There is an unmet need for specific biomarkers for the early diagnosis of KD. Methods: Eighty-five KD patients suffering from acute-phase and subacute-phase KD, 40 healthy children, and 40 febrile children comprised the study cohort. An enzyme-linked immunosorbent assay was used to measure plasma levels of C1q, C1q-circulating immune complex (C1q-CIC), mannan-binding lectin-associated serine protease (MASP)-1, factor B, C4d, C3d, C5a, C5b-9 and CD59. results: Plasma concentrations of factor B and C5a in the acute phase were lower than those in healthy and febrile control groups (all P < 0.05). Compared with acute-phase KD patients, plasma concentrations of C1q, factor B, and C3d in KD patients were increased significantly (P < 0.05), but those of C4d, MASP-1 and CD59 decreased significantly (P < 0.05), in patients with sub-acute KD. conclusion: These data suggest that more than one pathway in the complement system is activated in KD. Importantly, decreased plasma concentrations of factor B and C5a in the acute phase (6-10 d) could be employed as biomarkers for the early diagnosis of KD. k awasaki disease (KD) is an acute, self-limiting, nonspecific systemic vascular inflammatory syndrome. KD is considered to be caused by infectious agents in genetically susceptible children. The diagnosis of KD is dependent upon clinical manifestations; definitive diagnostic markers are lacking. The pathogenesis of KD is characterized by immune injury to endothelial cells (1) that results in systemic vasculitis or aneurysms in coronary arteries (2).Vascular endothelial cells are a source of complement and complement regulatory factors. Activated complement can form complement fragments (e.g., C3, C4d, Bb) and the membrane attack complex (MAC) on the cell surface (3). The MAC can mediate the inflammatory response by killing anucleate cells and bacteria, as well as causing cells to secrete a large number of cytokines and growth factors (4). Animal studies have shown that coronary atherosclerotic lesions appear not only during complement activation, but also during complement deposition, which results in tissue injury (5). It also has been demonstrated that complement components are accumulated in cryoglobulinemic vasculitis (6). Other studies have reported dysfunction of vascular endothelial cells (7) and the classical pathway of complement activation in all three layers of aneurysms (8).With the evidence stated above, we speculated that activation of the complement system might be involved in the pathogenesis of KD, and that activated complement factors could be employed as early diagnostic markers for KD. To test this hypothesis, we investigated plasma levels of various complement components in children with acute KD and subacute KD. RESULTS Changes in Plasma Concentrations of Complement FactorsC1q and C1q-circulating immune complex (C1q-CIC). C1q is a factor of the classical pathway of complement activation. The plasma level of C1q was sig...

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“…However, CD59 levels in plasma were found to be low at the early stage of KD (Song et al, 2016). In agreement with our results, plasma CD59 concentrations increased in acutephase KD patients compared with subacute-phase KD patients (Zou et al, 2015). Therefore, this inconsistent result requires further investigation.…”

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