Abstract: FR-PO1184
The Donor-Specific Antibody-Negative Paradox: Early Mixed Rejection with Microvascular Inflammation
Session Information
- Transplantation: Clinical - Rejection, Biomarkers, and Pharmacology
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Pujari, Ashwini S., University of Louisville, Louisville, Kentucky, United States
- Nouman, Muhammad Khuram, University of Louisville, Louisville, Kentucky, United States
Introduction
Antibody-mediated rejection (AMR) may occur in the absence of donor-specific antibodies (DSA) and C4d staining, creating diagnostic uncertainty. Microvascular inflammation has emerged as a key marker of antibody-mediated injury. We report a case of early mixed rejection with concurrent possible IgA nephropathy highlighting this challenge.
Case Description
A 41-yr-old woman with end-stage kidney disease due to HTN and nephrolithiasis underwent deceased donor kidney transplantation on 11/2025. She received thymoglobulin and methylprednisolone as part of induction. She was on tacrolimus and mycophenolate for her maintenance immunosuppression regimen. Early post-transplant course was complicated by gastrointestinal intolerance and influenza infection, followed by rising creatinine to 7.5 mg/dL.
Allograft biopsy demonstrated acute T cell–mediated rejection (Banff 1A) with significant microvascular inflammation (glomerulitis g3, peritubular capillaritis ptc1), suspicious for AMR despite negative C4d staining and DSA. Acute tubular injury and mesangial IgA deposits were also present.
She was treated with pulse steroids, plasmapheresis, and IVIG. Rituximab was initiated but not fully tolerated. Her course was complicated by thrombocytopenia likely multifactorial from drugs, infection and possible thrombotic microangiopathy given the evidence of peripheral hemolysis. She was switched to cyclosporine from tacrolimus. Non-HLA antibodies were positive for anti-endothelial cell antibodies (Initial titers ECS1 201,ECS2-210 and post treatment was 112 and 135 respectively). Renal function partially improved, with creatinine stabilizing around 2.5 mg/dL.
Discussion
C4d-negative, DSA-negative microvascular inflammation (MVI) is an increasingly recognized phenotype of kidney allograft injury. This case emphasizes the pathogenic role of non-HLA antibodies in antibody-mediated rejection and supports consideration of non-HLA antibody testing in patients with unexplained MVI, as early diagnosis and treatment may improve graft outcomes.