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Frequency and Clinical Implications of Development of Donor-Specific and Non–Donor-Specific HLA Antibodies after Kidney Transplantation

Maryvonne Hourmant^*, Anne Cesbron-Gautier, Paul I. Terasaki, Kazuo Mizutani, Anne Moreau, Aurélie Meurette^*, Jacques Dantal^*, Magali Giral^*, Gilles Blancho^*, Diego Cantarovich^*, Georges Karam^||, Gilles Follea, Jean-Paul Soulillou^* and Jean-Denis Bignon

^* Department of Nephrology and Clinical Immunology; Laboratory of Pathology; ^|| Department of Urology, Hôtel-Dieu, CHU de Nantes; Laboratory of Histocompatibility, National Blood Bank, Nantes Cédex, France; and Terasaki Foundation Laboratory, Los Angeles, California

Address correspondence to: Dr. Maryvonne Hourmant, Service de Néphrologie et d’Immunologie Clinique, Immeuble Jean Monnet, Hôtel-Dieu, 44093 Nantes Cédex, France. Phone: 33-240-08-74-45; Fax: 33-240-08-74-11; maryvonne.hourmant{at}chu-nantes.fr

Received for publication December 23, 2004. Accepted for publication June 24, 2005.

The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non–specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.

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