Kidney Week

Abstract: SA-PO879

When You Close a Door, a Window Opens: A Case of Dupilumab-Induced Autoimmune Glomerulonephritis

Session Information

• Glomerular Diseases: Case Reports - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Alanzi, Meshaal, Temple University, Philadelphia, Pennsylvania, United States

Meshaal Alanzi, MD

• Gillespie, Avrum, Temple University, Philadelphia, Pennsylvania, United States

Avrum Gillespie, MD

• Mani, Kishore Kumar, Temple University, Philadelphia, Pennsylvania, United States

Kishore Kumar Mani, MD

• Boyle, Suzanne, Temple University, Philadelphia, Pennsylvania, United States

Suzanne Boyle, MD, MS

• Koul, Sheetal, Temple University, Philadelphia, Pennsylvania, United States

Sheetal Koul, MD

Introduction

Dupilumab, a monoclonal antibody that blocks IL-4 and 13, is indicated for atopic dermatitis management. Eosinophilic granulomatosis with polyangiitis (EGP) has been reported with dupilumab use. We report a case of AKI from lupus-like glomerulonephritis following dupilumab, suggesting that blocking IL-4 and 13 may be linked to autoimmunity.

Case Description

A 61-year-old man with a history of an orthotopic liver transplant for HCV-related cirrhosis five years prior and non-proteinuric CKD (baseline creatinine 2.3 mg/dl) was admitted for generalized fatigue, mild abdominal pain, nausea, and poor appetite. Serum creatinine was 8 mg/dl.
Four months before, he started Dupilumab for resistant atopic dermatitis. Further testing revealed normocytic anemia with Hb of 6.5 g/dL and thrombocytopenia 103 K/mm³. Urinalysis showed hematuria; urine protein to creatinine ratio 4216 mg/gram. Complement C3/C4 normal, ANA, anti-ds DNA, and rheumatoid factor negative. c-ANCA titer was 1:320 (negative for anti-PR-3 and MPO).
An ANCA-mediated GN was initially suspected. However, a kidney biopsy revealed a membranoproliferative glomerulonephritis with cellular crescents and a diffuse tubulointerstitial inflammatory infiltrate with "full house" staining on immunofluorescence, consistent with lupus-like nephritis. The patient was managed with steroids (500 mg methylprednisolone for three days, then 1 mg/kg with taper). Ultimately, he needed regular hemodialysis.

Discussion

In this case, Dupilumab was the most likely cause of this “full-house” ANCA-positive nephritis. Dupilumab has also been associated with EGP. The potential mechanism is that blocking IL4 increases autoimmunity.
IL-4 is considered an immunoregulatory cytokine with pleiotropic effects on antibody production, inflammation, and T-cell responses. It is suggested that IL-4 has a protective role against autoimmunity as it suppresses T-cell activity and tissue inflammation. In one mouse strain, the pathogenic autoantibody subclasses (IgG21 and IgG3) were suppressed by IL-4. Thus, mice with increased IL-4 had low levels of IgG3 and IgG2a subclasses of anti-DNA antibodies with high IgG1 levels, which is considered protective against lupus-like nephritis development. Consequently, suppressing IL-4 might lead to increased autoantibody subclasses that deposit in the kidney, inducing inflammation.