Monoclonal and polyclonal immunoglobulin G deposits on tubular basement membranes of native and pretransplant kidneys: A retrospective study

Anri Sawada,Tomomi Tamura,Sekiko Taneda,Shigeru Horita,Kazunari Tanabe,Motoshi Hattori,Akira Shimizu,Kazuho Honda,Yoji Nagashima,Kosaku Nitta,Hideki Ishida,Junki Koike,Masayoshi Okumi

doi:10.1111/pin.13092

Abstract

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.

Highlights

Monoclonal tubular basement membrane immune deposits (TBMID) are identified by renal biopsy and are associated with progression of interstitial injury in renal allograft
The rate of immunoglobulin G (IgG) TBMID was relatively common in the case of diabetic nephropathy (31.3%) and lupus nephritis (25.5%), but rare in IgA nephropathy (IgAN) (1.1%)
We have previously reported the association of monoclonal IgG TBMID with the formation of electron-dense deposition (EDD) in the TBM with subsequent progression of interstitial fibrosis and tubular atrophy (IFTA) [10]

Summary

Methods

We recruited all patients between April 2008 and March 2018 at Tokyo Women’s Medical University with data of native kidney and zero-hour kidney biopsy. For IF, 2-μm cryostat sections were dried and stained with fluorescein isothiocyanate (FITC)-conjugated polyclonal antibodies against IgG; IgA; IgM; complement components 3, 1q, and 4d (C3c, C1q, and C4d); fibrinogen; κ light chain; and λ light chain (Dako Corp., Carpinteria, CA, USA). Measurement of IgG was performed on 2-μm cryostat sections stained with FITC-conjugated monoclonal antibodies against IgG1, IgG2, IgG3, and IgG4 (The Binding Site Inc., San Diego, CA, USA). Monoclonal IgG TBMID was identified by the presence of monoclonal staining for a single light-chain isotype and a single-heavy chain subclass in TBM samples. This study and all its protocols were approved by the ethics committee at Tokyo Womens Medical University (No 5415)

Results

Discussion

Conclusion