Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy

Abstract

Intrinsic antigen-related MN was more strongly associated with complement activation by the lectin pathway, which may contribute to a less favorable clinical outcome.

Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation

“…The exact contribution of each of the three complement pathways in MN remains unknown. The lectin pathway may play an important role, since the prevalence and staining intensity of mannose-binding lectin (MBL) deposits were much higher in PLA2R1-positive patients than in patients without MBL deposits [29]. The staining intensity of MBL in glomeruli also correlated with the IgG4 staining intensity and was an unfavorable predictor for remission of proteinuria and renal dysfunction.…”

“…This suggests that the alternative or lectin pathways might be involved in complement activation. Hayashi et al detected glomerular deposits of C4d, C3d, and C5b-9 in all patients while mannose-binding lectin (MBL) and C1q were detected in only 43% and 46% of patients, respectively [29]. One or more complement pathways may be activated after the formation of immune deposits and can vary among MN patients.…”

C4d in Native Glomerular Diseases

“…MBL was present in 43% of patients suggesting LP activation, but C1q was also noted in about 46% of patients (in both intrinsic antigen related and unrelated), indicating CP activation. Patients with intrinsic antigen related group had more intense staining for MBL, which correlated with IgG4 staining and was associated with less chance of proteinuria remission and with renal dysfunction [40]. In a study of 69 patients with primary MN, C4d (via IHC) deposition with C1q was noted in 12 patients (indicating CP pathway activation), C4d without C1q deposition noted in 46 patients (indicating LP activation), and no deposition of C4d or C1q in 11 patients suggesting activation via AP pathway [41].…”

Clinical significance of C4d deposition in renal tissues from patients with primary Sjögren’s syndrome—A preliminary study

“…The contribution of complement to MN (primary and secondary) was documented elsewhere(Ma, Sandor &Beck, 2013). Besides C3, the component of the alternative pathway, glomerular deposition of C4d and MBL were detected in PMN, indicating involvement of the lectin pathway(Hayashi et al, 2018;Hui et al, 2014). The lectin pathway of complement may be possibly triggered by the in situ formed immune complexes comprising the IgG4 type of anti-PLA2R antibodies(Sinico et al, 2016).…”

“…Primary membranous nephropathy (PMN) is a kidney-specific disease with increased proteinuria and pathological characteristics of sub-epithelial immune complex deposition (predominantly IgG4 and C3 deposition)(Sinico et al, 2016). PMN is characterized by the presence of serum autoantibodies against the podocyte component M-type phospholipase A2 receptor (PLA2R) in approximately 70% of patients(Beck et al, 2009) and anti-thrombospondin type 1 domain containing 7A (THSD7A) antibodies in approximately 10% of those with negative anti-PLA2R antibodies (nearly 3% of patients with intrinsic antibodies related MN)(Hayashi et al, 2018;Tomas et al, 2014). The mannose-binding lectin pathway of complement activation is involved in PMN, as evidenced by sub-epithelial deposition of hypogalactosylated IgG4 and C3 and 100% glomerular C4d deposition without C1q co-deposition(Hui et al, 2014).…”