Lectin complement pathway and diabetes mellitus in the pathogenesis of membranous nephropathy

Abstract

Introduction: Membranous nephropathy (MN) is a glomerulonephritis with growing incidence and its pathogenesis still remains unclear, despite discoveries of many new antigens. The understanding of MN pathogenesis has moved from antigen-antibody arena to the complement activation through the lectin pathway. Aim: Confirm the role of lectin complement pathway in the pathogenesis of the disease and reveal the special role of diabetes mellitus (DM) in idiopathic MN (iMN). Materials and methods: Materials from 72 renal biopsies with proven MN are used for immunohistochemistry staining (IHC) for phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4 and mannose-binding lectin (MBL). Patients are separated in three groups: primary MN (pMN), iMN and secondary MN (sMN). Relationship between the type of MN and IHC deposition is studied. Patients with diabetes mellitus are presented separately. Patients are divided according to IHC results into triple positive/+/, double positive/+/, positive /+/ and triple negative/-/. Results: Triple /+/ for PLA2R/ IgG4/ MBL, double /+/ for PLA2R/IgG4 and /+/ for PLA2R expression are found only in patients with pMN. Double /+/ cases for IgG4/MBL are found predominantly in patients with iMN. No cases of double /+/ for PLA2R/MBL are found. Patients with DM represent 50% of patients with iMN, and 50% of them are double /+/ for IgG4/MBL. Conclusions: Activation of the lectin complement pathway is essential in MN. The deposition of MBL is always associated with deposition of IgG4 in pMN and iMN. IgG4 in sMN is not associated with MBL deposition. Possible “switch” from diabetic nephropathy (DN) to MN can be discussed since diabetes is associated with abnormal protein glycosylation and increased activation of lectin pathway.