Glomerular mannose-binding lectin deposition is a useful prognostic predictor in immunoglobulin A nephropathy

Abstract

SummaryThere is accumulating evidence to support a hypothesis of the activation of the lectin complement pathway in immunoglobulin A nephropathy (IgAN). The glomerular deposition of mannose-binding lectin (MBL), an initiator of the lectin pathway, has been identified, but its clinical significance has not been defined consistently. The aim of the present study was to investigate the value of glomerular MBL deposition as a useful histological biomarker in evaluating the severity and predicting the prognosis of IgAN. We included all consecutive patients with biopsy-proven primary IgAN from December 2008 to July 2010. Renal deposition of MBL was detected by immunofluorescence. The biopsy material from 131 patients (72 men) was thus used for MBL staining. The deposition of MBL was observed in a predominantly mesangial pattern in 45 patients (34·35%), which presented as global or segmental deposition. Compared with the patients without glomerular MBL deposition, those with glomerular MBL deposition had more severe proteinuria, decreased renal function, lower levels of serum albumin and a greater possibility of hypertension at the time of renal biopsy; they had more severe histological changes according to the Oxford classification (i.e. mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and tubular atrophy/interstitial fibrosis), and their ratio presented an increase as the histopathological phenotypes segregated according to Lee's classification; furthermore, the follow-up data demonstrated that they had a lower renal remission rate. In conclusion, glomerular MBL deposition may predict a poor prognosis, and thus can be a new prognostic factor in IgA nephropathy.

Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

“…It is deposited in the renal mesangium and stimulates mesangial cells or activates complement pathways to induce renal damage [31,32]. SIgA is secreted by B cells in mucosal cells, where it enters the circulation and is finally deposited in the mesangium.…”

Immunoglobulin A nephropathy: a pathophysiology view

“…Mesangial deposits of MBL and C4 and/or C4 catabolites are potential markers for the progression of IgAN [103,104]. In contrast, patients with MBL deficiency tend to show better clinical presentation and lower levels of serum creatinine and proteinuria than patients without MBL deficiency [105,106]. N-glycans present on the heavy chains of secretory IgA1 are candidate ligands for lectin pathway activation [107].…”

Biomarkers in IGA Nephropathy

“…Zhou et al studied matrix alterations associated with IgAN injury and found that decorin and its analog biglycan -pericellular matrix proteoglycans involved in fibrillogenesis and the regulation of the cell cycle [68] -were increased by 45.1 and 136.6%, respectively [56]. Recognizing this injury, MBL has been proposed to attack damaged and/or apoptotic renal cells, which results in its accumulation in renal tissue and expansion of the mesangial matrix [69]. Immunofluorescence studies on 131 IgAN patients yielded positive staining of MBL in 35% of patients [69].…”

“…Recognizing this injury, MBL has been proposed to attack damaged and/or apoptotic renal cells, which results in its accumulation in renal tissue and expansion of the mesangial matrix [69]. Immunofluorescence studies on 131 IgAN patients yielded positive staining of MBL in 35% of patients [69]. Clinically, MBL deposition results in more severe proteinuria, decreased renal function, lower levels of serum albumin, a greater probability of hypertension and an overall poorer prognosis [69].…”