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#45
ACUTE HUMORAL REJECTION DUE TO NON-COMPLEMENT BINDING HLA CLASS II ANTIBODY.
Billie S. Fyfe, MD , Anil M. Kumar, MD and Robert F. McAlack, PHD . Philadelphia PA, Drexel University College of Medicine, 19102, Department of Pathology and Laboratory Medicine and Philadelphia PA, USA, Drexel University College of Medicine, 19102, Department of Surgery,Division of Transplantation and Medicine .
CASE STUDY
Background: Typically, severity of humoral rejection depends on the target HLA antigen and ability of the formed antibody (AB) to bind and initiate the complement cascade. We present a case of graft destruction due to Class II AB without the ability to bind complement in-vitro.
Design: Circulating anti-HLA AB was identified using both a complement-dependent assay (LCT-One Lambda) and an ELISA assay (LAT-OneLambda). Crossmatch (CM) was performed using a complement-dependent test procedure enhanced with rabbit anti-human globulin. Resected kidney was submitted for histological analysis as well as direct immunofluorescence (IF).
Results: Pretransplant, this 33 year-old recipient had no Class I antibody but did have complement binding anti-Class II against DR11 and DR 17. The donor organ was mismatched at two Class I loci (A32 and B64) and one Class II locus (DR15). CM was negative against both Class I and Class II. Within days, an anti-DR15 IgG AB was detected by ELISA assay but not by complement-dependent LCT assay. The kidney was removed for humoral rejection, confirmed histologically, with extensive microvascular thrombosis, ischemic injury and patchy mixed inflammation with numerous leukocytes. IF showed marked vascular C3 and fibrinogen deposition without AB deposition.
Conclusion: The current case demonstrates that Class II specific, non-complement binding antibodies may still be capable of causing graft destruction via immunologic methods with activation of the alternate complement pathway.