Anti-GBM disease following CTLA4 blockade in a patient with metastatic melanoma

Abstract

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) antagonists are currently being investigated in patients with metastatic malignant melanoma. It is proposed that this therapy will upregulate T-cell responses to melanoma cells while simultaneously targeting regulatory T lymphocytes (Tregs) which are known to suppress the host's immune response to cancer cells. In some of these patients, immune-mediated adverse events such as enterocolitis, dermatitis, uveitis and hepatitis have been observed. We report a case of a 50-year-old man presenting with cough, fever, macroscopic haematuria and oligoanuric kidney failure following treatment with the CTLA4 antagonist tremelimumab for metastatic malignant melanoma. Kidney biopsy demonstrated crescentic glomerulonephritis and strong linear glomerular basement membrane (GBM) staining for IgG and C3; serum anti-GBM antibody level was markedly elevated (>200 U/ml). © 2009 The Author. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.