PLA2R-Negative Membranous Nephropathy Presenting as a Prodrome of IgG4-Related Autoimmune Pancreatitis

Abstract

Membranous nephropathy (MN) with tubulointerstitial nephritis (TIN) is an established manifestation of immunoglobulin G4 (IgG4)-related disease (IgG4-RD). A pathological feature aiming to distinguish between primary and secondary MN is the presence or absence of glomerular staining for phospholipase A2 receptor (PLA2R), respectively. Isolated MN without TIN has been rarely reported in the context of IgG4-RD. This case report describes a patient with a history of MN successfully treated with steroids and cyclophosphamide, who, 3 years later, presented with unexplained exacerbation of diabetes mellitus due to IgG4-related autoimmune pancreatitis. Pancreatitis was treated, and diabetes improved after treatment with steroids. Based on the presence of isolated IgG4 glomerular capillary deposits along with negative staining for PLA2R and the metachronous appearance of autoimmune pancreatitis, MN was retrospectively classified as secondary to IgG4-RD. Isolated IgG4-positive/PLA2R-negative MN without TIN can be a prodrome of IgG4-RD, reminiscent of MN secondary to neoplasms.

Keywords: Autoimmune pancreatitis; Diabetes mellitus; Endoscopic ultrasound; IgG4-related disease; Membranous nephropathy; PLA2R.

Fig. 1

Kidney biopsy findings. a Strong global granular IgG staining along the capillary walls; IgG, ×400. b, c Strong global fine granular IgG4 staining along the capillary walls; IgG4, ×400. d Negative PLA2R immunohistochemical staining; ×200. e Membranous nephropathy without tubulointerstitial nephritis; Masson, ×100. f Low-power magnification (×40) showing diffuse IgG4 glomerular staining with no staining in the interstitium. g Membranous nephropathy without morphological signs of secondary etiology (without mesangial cellularity); Masson, ×400. h Membranous nephropathy without morphological signs of secondary etiology (without mesangial cellularity); Silver, ×400.