A. Nikaein

Hla Compatibility And Liver Transplant Outcome Improved Patient Survival by Hla and Cross-matching

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P=0.0051 and P=0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA ≤ 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P<0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA ≥ 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P<0.0001). Analysis of HLA compatibility demonstrated a significant impact on patients survival, comparing only 0–2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P=0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P=0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P=0.04).

Graft-versus-Host Disease in a Liver Transplant Recipient

Excerpt The classic requirements for graft-versus-host disease (GVHD) (1) exist in recipients of liver allografts: 1) The donor liver and recipient are histo-incompatible; 2) lymphocytes within the...

Characterization of skin-infiltrating cells during acute graft-versus-host disease following bone marrow transplantation using unrelated marrow donors.

To characterize skin-infiltrating T lymphocytes during acute GVHD, skin biopsies were obtained from two patients who received unrelated marrow matched for HLA-A, -B, -DR, and -DQ but mismatched for -DP. A total of 120 T-cell clones were generated. Phenotype analysis of the clones showed that the majority of cells were CD4+ and expressed alpha/beta TCR. HLA-DP oligonucleotide genotyping of the clones revealed the presence of lymphoid chimerism. PLT assay showed the lack of HLA specificity, including mismatched HLA-DP. However, mAb to HLA antigens blocked proliferation of the majority of the clones, indicating that the clones recognized HLA-associated molecules. Interestingly, proliferation of two CD4+ T-cell clones was inhibited by class I mAb. A few of the clones revealed augmented proliferation in the presence of CMV antigens and a few revealed cytolytic activity. The above study suggests that (a) CD4+ helper T cells may be primarily responsible for immunopathogenesis of skin manifestations during acute GVHD, (b) there is a mixed lymphoid chimerism in skin during acute GVHD, (c) HLA-DP may not be a factor contributing to the development of acute GVHD, (d) the peptide of the HLA groove or superantigen associated with HLA molecules may be the stimulatory antigen, and (e) CMV antigens appear to stimulate some of the skin-infiltrating T lymphocytes.

Therapeutic and Immunologic Advances in Psoriasis

Psoriasis is a common skin disorder with varied clinical presentations, ranging from small localized plaques to widespread inflammatory disease with marked exfoliation. Advances in therapy now allo...