Serial Ten‐Year Follow‐Up of HLA and MICA Antibody Production Prior to Kidney Graft Failure

Abstract

The role of HLA antibodies in chronic allograft rejection was examined utilizing a unique resource of sera collected annually and stored over a 12-year period from patients with rejected or retained grafts. In patients selected for not having preformed HLA antibodies, 679 postoperative serial serum samples from 39 patients who rejected their grafts and 26 with functioning grafts were tested for HLA Class I and Class II antibodies by flow cytometry and for MICA antibodies by cytotoxicity on recombinant cell lines. HLA antibodies were found in 72% of patients who rejected grafts, compared to 46% with functioning transplants (p < 0.05). In addition, the incidence of IgG HLA plus MICA antibodies was higher (77%) among those with failed transplants than those with functioning transplants (42%) (p < 0.01). Finally, if patients with IgM anti-HLA antibodies were included, 95% of the 39 patients who rejected their grafts had HLA or MICA antibodies, compared to 58% with functioning grafts (p < 0.01). Patients who rejected transplants had HLA and MICA antibodies more frequently than those with functioning grafts. These antibodies found in the peripheral circulation, were not necessarily donorspecific, but their association with failure is consistent with a causality hypothesis.

Accommodation of grafts: Implications for health and disease

“…Explaining "the Paradox" of Frequent Accommodation and Low Prevalence of Anti-HLA Antibodies Anti-HLA antibodies are generally considered detrimental for organ transplants, and the presence of these antibodies in the blood of a transplant recipient predicts rejection [17][18][19][20]. Consistent with this concept, anti-HLA antibodies are detected infrequently in those with normally functioning transplants.…”

Antibody-Mediated Renal Allograft Rejection

“…Increased risk for graft loss mainly affected those with intermediate graft dysfunction at the time of the antibody measurement (creatinine 2.0 to 3.9 mg/dl) (37). Antibodies to MICA (a polymorphic class I-related antigen) are also associated with late graft failure, even in the absence of measurable HLA antibodies (38).…”

Antibody Mediated Rejection

“…As mentioned earlier (20), MICA antibodies were associated with kidney transplant failures in addition to HLA antibodies. Evidence that other antigens, which unlike MICA are not linked to HLA, might be responsible for rejection was described recently by Opelz (34).…”

“…In an extensive study of 39 patients who rejected a kidney graft and 26 with functional grafts, 679 postoperative serial serum samples were tested (20). IgG and IgM HLA antibodies were found in 72% of patients who rejected grafts, compared with 46% with functioning transplants (P Ͻ 0.05).…”