Atypical Presentation of Atypical Anti-Glomerular Basement Membrane Disease
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
- Andrawes Barbara, Faten Yousef, Galilee Medical Center, Nahariya, North, Israel
- Zeitun, Teuta, Galilee Medical Center, Nahariya, North, Israel
- Jiries, George, Galilee Medical Center, Nahariya, North, Israel
- Kruzel Davila, Etty, Galilee Medical Center, Nahariya, North, Israel
Anti-glomerular basement membrane (anti-GBM) disease is a rare aggressive autoimmune disorder characterized by circulating anti-GBM Antibodies (Ab) leading to crescentic necrotizing glomerulonephritis with linear deposits of immunoglobulin G (IgG) along the GBM. As opposed to the classic anti-GBM disease, atypical anti-GBM glomerulonephritis is characterized by an indolent clinical course, undetectable circulating anti-GBM Ab, endocapillary proliferation with only few crescents and linear IgG staining of the GBM. Herein, we present a case of atypical manifestation of atypical anti-GBM disease and emphasize the therapeutic dilemmas and challenges.
24-year-old male with a 3 weeks history of vomiting, was admitted to the hospital with severely impaired kidney function (creatinine 17 mg/dl), massive proteinuria without pulmonary involvement. Anti-nuclear, anti-neutrophilic cytoplasmic, and anti-GBM Ab were negative (anti-GBM was examined by indirect immunofluorescence (IF) assay, and enzyme-linked immunosorbent assay (ELISA)). Kidney biopsy demonstrated 100% cellular crescents with linear polytypic IgG staining of the GBM and C3 on IF. Hemodialysis was started. The patient was treated with high-dose steroids, cyclophosphamide and plasma exchange, as for classic anti-GBM disease. As opposed to classic anti-GBM disease, duration of plasmapheresis could not be dictated in the absence of detectable anti-GBM antibodies. The clinical course was ominous without improvement of his kidney function.
The patient’s clinical course and pathological findings were consistent of classic anti-GBM disease. Therefore, the absence of circulating anti-GBM Ab was surprising and did not suit the aggressive course of his kidney disease and pathological findings. Several theories had been proposed to explain the undetectable anti-GBM Ab including autoantibodies directed against GBM epitopes other than a3NC1, quaternary epitopes of native a345NC1 hexamers or high avidity for anti GBM ab along the glomeruli leading to undetectable circulating ab. Modified assays to detect a wide range of antigens or epitopes, using more sensitive techniques like biosensors, can unmask circulating anti-GBM antibodies and help in making therapeutic decisions regarding duration of plasmapheresis and immunosuppression therapy well as timing of kidney transplantation.