Abstract
Posttransplant antiglomerular basement membrane (anti-GBM) disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA). On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG.
Highlights
Alport syndrome is a genetic disorder caused by mutations in COL4A3, COL4A4, and COL4A5 genes, impairing assembly of type IV collagen
With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months
We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM enzyme immunoassay (EIA) and may respond to treatment with plasmapheresis and IVIG
Summary
Alport syndrome is a genetic disorder caused by mutations in COL4A3, COL4A4, and COL4A5 genes, impairing assembly of type IV collagen. Anti-GBM nephritis is usually associated with the presence of circulating IgG antibodies to the noncollagenous domain of alpha 3(α3) Type IV collagen, manifesting as linear IgG deposition along the GBM on immunofluorescence staining. These patients develop hematuria, proteinuria, and end-stage renal disease. When patients with Alport syndrome receive renal transplants, posttransplant anti-GBM nephritis occurs in 3–5% of patients [4, 5, 7]. We describe a case of Alport syndrome with development of posttransplant anti-GBM nephritis with negative anti-GBM antibodies by enzyme immunoassay (EIA) who was found to have circulating antibodies to another epitope at the noncollagenous region of type IV collagen. The patient was treated with plasmapheresis and IVIG and responded excellently with preservation of renal allograft function
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