Synthesis of New and Memory HLA Antibodies From Acute and Chronic Rejections Versus Pregnancies and Blood Transfusions

Abstract

Background This study compared HLA antibody (abs) production following acute (AR) and chronic (CR) rejection with HLA abs production following blood transfusions (TF) or pregnancies (P) among kidney and kidney pancreas transplant candidates. Methods Serum samples from 145 patients were screened for anti-HLA abs by flow cytometry using beads coated with purified HLA molecules. Among these patients, nine had lost their graft due to AR; 13, CR; six had been immunized by a single P; 20 by no more than two TF; 28 had no documented immunization; and 69 had multiple immunizations. A Fisher exact test was used for the statistical analysis. Results Neither a single P nor a couple of TF by themselves immunized primary transplant recipients ( P = .17, and P = .42, respectively). However, multiple P and TF together provided a potent immunogenic stimulus ( P = .00001). In contrast, a single allograft loss induced a strong anti-HLA response ( P = 1.03 × 10 −8). Following AR, anti-class I and II abs ( P = .001), and following CR, anti-class II abs developed ( P = .03). Waitlisted female candidates had significantly high PRA values than men ( P = .00005), possibly because women had received significantly more immunizations than men ( P = 4.0 × 10 −10). Summary Patients are likely to produce both class I and II HLA abs following AR and only class II abs following CR. A couple of TF or a P may not be immunogenic; however, together they have great potential to sensitize female candidates. Perhaps that is why waitlisted women are far more immunized than waitlisted men.