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

Abstract

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.

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

“…Whereas the robust antibody response in early AMR results in complement-mediated lytic injury of the endothelium and rapidly progressive allograft dysfunction allowing an early diagnosis, the smoldering generation of de novo DSA observed in late AMR results in nonlytic complementmediated injury, partial accommodation, and slow allograft dysfunction. [25][26][27][28] Whether the differences in the nature of the Table 3. CLINICAL RESEARCH www.jasn.org immune response influence the response to therapy in these entities has yet to be studied.…”

Antibody-Mediated Renal Allograft Rejection

“…Several studies have shown that circulating anti-HLA class I or II antibodies, either donor reactive (35,36) or de novo, non-donor reactive (36,37), are found in a substantial fraction of renal allograft recipients, and these are associated with later graft loss. Among 2278 recipients who were followed prospectively, graft failure 1 yr later was greater in those with alloantibodies than in those without (8.6 versus 3.0%; P Ͻ 0.0001).…”

Antibody Mediated Rejection

“…Among nine patients with antibodies with biopsies, six had C4d staining, whereas in 11 patients without antibodies, none had C4d staining (23). In 1229 patients who were investigated 1 to 5 yr after transplantation, 5.5% had DSA, 11.3% had non-DSA, and 83% had no HLA antibodies (24). The presence of either DSA or non-DSA correlated with lower graft survival, poor transplantation function, and proteinuria.…”