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Biomedical subjects

Paul Terasaki

Publications and source records attributed to Paul Terasaki.

6 recordsLinked to original sources

Association of kidney transplant failure and antibodies against MICA.

Despite the progress in renal transplantation, acute rejection and graft failure still occur and chronic rejection continues to be the main problem in long-term allograft survival. Although kidney transplant rejection has been linked to anti-HLA antibodies, not all patients with failed kidney transplants have anti-HLA antibodies, indicating that other loci may be involved. Sera of 63 patients who experienced kidney rejection were compared against sera of 82 patients with functioning transplants. Sera were examined for IgG and IgM anti-HLA Class I and II antibodies. They were also tested by cytotoxicity against panels of 26 endothelial cell lines, 8 MHC class I chain-related gene A (MICA) recombinant cell lines, and 28 B lymphoblast cell lines. Among patients whose transplants failed, 65% had anti-HLA antibodies compared with 45% of those with functioning kidneys (p < 0.05). Similarly, among those whose transplants failed, 41% had anti-endothelial cell antibodies in contrast to 22% in functioning patients (p < 0.05). Among patients whose grafts failed, 52% had anti-MICA antibodies versus 21% of those with functioning grafts (p < 0.001). Eleven patients with failed grafts and 32 with functioning grafts were negative for all of the above. However, 6 of the former and 7 of the latter showed positive cytotoxicity against B lymphoblasts (p < 0.05). Taking all antibodies together, 92% of patients with graft failure had antibodies as opposed to 70% of patients with functioning grafts (p < 0.001). We postulate that antibodies against HLA, MICA, endothelial cells, and B lymphoblasts could be independently involved in the slow process of chronic graft failure.

B-Lymphocytes↗

Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure.

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 donor-specific, but their association with failure is consistent with a causality hypothesis.

Adult↗

Serum creatinine as a predictor of transplant survival and death.

Taking ALL patients transplanted in a given calendar year, we have shown that serum creatinine values have gradually decreased over the past 15 years. Donor age was a major factor influencing serum creatinine. This was followed by the recipient sex. Of lesser importance was the different immunosuppressive drugs employed, and whether the donor was deceased or living. The strong predictive value of serum creatinine was shown at various times after transplantation. Also, one year prior to failure, the creatinine values were very significantly elevated. A similar finding was noted one year prior to the death of patients with a functioning graft.

Adult↗

Maintenance immunosuppressive treatment and graft half-life.

Longer graft half-lives were associated with Caucasian race, living donors, younger donor age. The HLA-matching effect on graft half-life was only significant when comparing HLA-matched transplant recipients with recipients of HLA-mismatched transplants, but not significant between mismatched recipients with varying degrees of HLA mismatch. First transplant recipients maintained on newer post-1995 immunosuppressive drug therapies, including tacrolimus, MMF and steroids, Neoral, MMF and steroids or Neoral, azathioprine and steroids, always had longer graft half-lives than patients on pre-1995 CsA protocols. The difference in graft half-lives between new and old protocols reached statistical significance in some categories. Patients on triple therapies had consistently longer graft half-lives than those receiving double therapies.

Adrenal Cortex Hormones↗