IgG4-Related Membranous Nephropathy After COVID-19 Vaccination: A Case Report

Abstract

Although immunoglobulin G4 (IgG4)-related kidney diseases are typically characterized by tubulointerstitial nephritis with abundant infiltration of IgG4-positive plasma cells and fibrosis, there have been relatively rare cases of IgG4-related glomerulonephritis. Several cases of IgG4-related disease (IgG4-RD) following coronavirus disease 2019 (COVID-19) mRNA vaccination have been reported. However, there are no reports of IgG4-related glomerulonephritis following COVID-19 vaccination. Herein, we present a case of IgG4-related membranous nephropathy (MN) occurring after COVID-19 vaccination. A 69-year-old Japanese male presented to our hospital with edema that started the day after his second COVID-19 vaccination. The patient exhibited nephrotic syndrome and was diagnosed with MN based on the results of a kidney biopsy. Although serum IgG4 levels were elevated to 946 mg/dL, no evidence of organ involvement suggestive of IgG4-RD was observed. Treatment with prednisolone and cyclosporine resulted in complete remission, and immunosuppressive agents were tapered. However, one month after discontinuing the immunosuppressive agents, the patient was readmitted with swelling around the submandibular glands and exertional dyspnea. Serum IgG4 level was markedly elevated at 2,320 mg/dL, and computed tomography revealed submandibular gland swelling and thickening of the interlobular septum and bronchovascular bundles in both lungs. The patient was diagnosed with IgG4-RD based on elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in the submandibular gland biopsy. Upon resuming treatment with prednisolone, the symptoms attributed to IgG4-RD improved within a few days. In cases of nephrotic syndrome following COVID-19 vaccination, it may be advisable to conduct detailed examinations to assess the possibility of the development of IgG4-RDs.

Keywords: covid-19 vaccine; igg4-related disease; igg4-related kidney disease; membranous glomerulopathy; severe acute respiratory syndrome coronavirus 2.

Figure 1. Histological examination of the kidney biopsy.

(A, B) Light microscopy analysis of the kidney biopsy. (A) Periodic acid-Schiff stain: Inflammatory cell infiltration including plasmacyte or interstitial fibrotic change was not observed (400×). (B) Periodic acid-methenamine-silver stain: Pinholes of GBM were observed (arrow) (400×). (C) Electron microscopy revealed finely granular dense deposits in the subepithelial space (arrowhead) and in the subendothelial space (arrow). GBM was diffusely thickened. Immunofluorescence analysis showed granular IgG and C3 deposition along the GBM and weak C1q deposition (200×). (D) IgG, (E) C3, (F) C1q.

Figure 2. Clinical course after the coronavirus disease 2019 (COVID-19) mRNA vaccination.

IgG4, immunoglobulin G4.

Figure 3. Computed tomography findings before and after resuming prednisolone.

(A–C) Unenhanced computed tomography (CT) findings before resuming prednisolone. CT of the neck shows the swelling of bilateral submandibular glands (arrowhead in A). CT of the chest shows the enlarged mediastinal lymph nodes (arrowhead in B), the interlobular septum thickening (arrowhead in C), and the bronchovascular bundle thickening (arrow in C). (D–F) Contrast-enhanced CT findings 2 weeks after resuming prednisolone. CT of the neck shows improvement in both submandibular gland enlargement (arrowhead in D). CT of the chest shows improvement in the mediastinal lymph nodes enlargement (arrowhead in E), improvement in the interlobular septum thickening (arrowhead in F), and bronchovascular bundle thickening (arrow in F).

Figure 4. Light microscopy of the submandibular gland biopsy.

(A) Hematoxylin-eosin stain: Infiltration of a large number of inflammatory cells, predominantly lymphocytes and plasma cells, accompanied by fibrous tissue proliferation. The acini and the ducts are destroyed (100×). (B, C) Immunohistochemistry showed IgG4-positive/CD138-positive cell ratio exceeding 40% (200×). (B) CD138, (C) IgG4