GLOMERULAR DEPOSITION OF MANNOSE-BINDING LECTIN (MBL) INDICATES A NOVEL MECHANISM OF COMPLEMENT ACTIVATION IN IGA NEPHROPATHY

Background. IgA nephropathy (IgA-N) is considered the most common glom erular disease in the world and leads to renal failure in a substantia l number of patients. Although many studies have looked at the pathoge nesis of the disease, many points need to be clarified, including the mechanism of complement activation. Recent studies have shown that man nose-binding lectin (MBL or mannose binding protein, MBP) initiates ac tivation of the complement cascade (lectin pathway) utilizing two type s of MBP-associated serine protease, namely MASP-1 and MASP-2. The pre sent study was undertaken to elucidate whether the lectin pathway was involved in the pathogenic mechanism of IgA-N. Methods. Forty-five ren al biopsy cases with IgA-N, 35 cases with other forms of glomeruloneph ritis (GN), and normal kidney tissues were collected and an immunohist ochemical study was performed using monoclonal antibodies against MBL and MASP-1. Furthermore, clinicopathological and serological features were also analysed in the patients with IgA-N. Results. Glomerular dep osition of MEL, which was accompanied by MASP-1, was detected in 11 of 45 (24.4%) cases with IgA-N, while it was detected in only one case w ith other forms of GN. The deposited MBL/MASP-1 was observed to associ ate with C3b/C3c and C5b-9 but not with IgG, IgM, Clq, C4c, or properd in. Compared with MBL/MASP-1 negative cases with IgA-N, the positive c ases with IgA-N were young and the renal biopsies had been performed a t an early stage of the disease. No significant correlation was found between glomerular deposition of MBL/MASP-1 and proteinuria, haematuri a, creatinine clearance, and serum levels of IgA, C3, or C4 at the tim e of renal biopsy. There were also no significant differences between MBL/MASP-1 positive cases and negative cases in the plasma levels of c irculating immune complexes or soluble C5b-9. Conclusion. The lectin p athway of complement activation, which is initiated by the MBL/MASPs c omplex, evidently contributes to the development of glomerular injury in a significant number of cases with IgA-N. In addition, these findin gs will add insight to the pathogenesis of IgA-N, including its relati on to infection, since MBL plays a crucial role in the host defense ag ainst various pathogens.