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Complement activation through the lectin pathway in patients with Henoch-Schönlein purpura nephritis
1Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo. mendo@med.nihon-u.ac.jp
Insights
Complement activation via the lectin pathway is implicated in Henoch-Schönlein purpura nephritis (HSPN) pathogenesis. This study found lectin pathway components in HSPN kidney biopsies, suggesting its role in early disease development.
Area of Science:
- Immunology
- Nephrology
- Complement System Biology
Background:
- Henoch-Schönlein purpura nephritis (HSPN) is a systemic vasculitis involving immune mechanisms and glomerular injury.
- The complement system plays a critical role in the pathogenesis of HSPN.
Purpose of the Study:
- To investigate the involvement of the lectin pathway, a complement activation route, in the pathogenesis of HSPN.
- To correlate lectin pathway activation with clinical and histological findings in HSPN patients.
Main Methods:
- Immunohistochemical analysis of renal biopsies from 10 HSPN patients.
- Evaluation of serum complement components, including mannose-binding lectin (MBL).
- Measurement of plasma complement activation products and comparison with IgA nephropathy and non-IgA GN groups.
Main Results:
- Glomerular deposition of MBL, MASP-1, C3b/C3c, C5b-9, and C4-bp was observed in 80% of HSPN patients.
- Elevated plasma C4d and C4-bp levels were found in HSPN patients compared to non-IgA GN.
- No significant difference in serum MBL levels was detected across HSPN, IgA nephropathy, and non-IgA GN groups.
Conclusions:
- Complement activation through the lectin pathway appears to be involved in the early stages of HSPN.
- The lectin pathway may represent a significant mechanism contributing to the pathogenesis of HSPN.
Abstract:
Henoch-Schönlein purpura nephritis (HSPN) is considered a form of systemic vasculitis of the small blood vessels with immune pathogenesis. In this disorder, the complement system is recognized as an important mechanism of glomerular injury. The aim of this study is to determine whether the lectin pathway, a novel pathway of complement activation, is related to the pathogenesis of HSPN. Renal biopsy material from 10 patients with HSPN was studied immunohistochemically and examined for a clinicopathologic correlation. Serum levels of complement components, including mannose-binding lectin (MBL), and plasma levels of complement activation products were also evaluated in these patients and compared with levels in patients with immunoglobulin A (IgA) nephropathy or mesangial proliferative glomerulonephritis (GN) without IgA deposition (non-IgA GN). Glomerular deposition of components of the pathway, MBL and MBL-associated serine protease (MASP-1), as well as C3b/C3c, C5b-9, and C4-binding protein (C4-bp), was detected in 8 of 10 patients. Although no significant correlation was found between glomerular deposition of MBL/MASP-1 and histological or clinical findings, the biopsies on all patients with MBL/MASP-1 deposits were performed within 20 weeks from the onset of disease. Levels of plasma C4d, the activation fragment of C4, and C4-bp, a soluble regulatory protein of the pathway, were greater in patients with HSPN than in those with non-IgA GN. However, there was no difference in serum MBL levels between the three groups of patients (HSPN, IgA nephropathy, and non-IgA GN). These results suggest that complement activation through the lectin pathway was involved at the onset of HSPN, and this mechanism might be important in the disease pathogenesis.