Neonatal alloimmune thrombocytopenia (NAIT) is usually induced by platelet-specific antibodies against HPA-1a (Zwa) or HPA-5b (Bra). Recently, low-frequency alloantigens on the platelet glycoprotein (GP) IIb/IIIa complex have been discovered as a cause for NAIT. In this report, a new low-frequency platelet-specific alloantigen, Iy, is described which induced severe NAIT. The corresponding antigen was detected in 1/249 unrelated German blood donors. Antibody binding assays with trypsin-digested platelets (ELISA, immunoprecipitation with biotin-labelled platelets) indicate that the antigen is not localized on the glycocalicin moiety of GP Ib alpha, but may be situated on the remnant moiety of GP Ib alpha, GP IX or GPIb beta. Apparently, Iy is not related to the HPA-2 (Ko) antigen system.
In order to determine whether HLA-A,B antigens of platelets are integral membrane constituents or
rather represent adsorbed plasma proteins, their presence in plasma and their adsorbability onto platelet membranes
was studied by in vitro and in vivo experiments. The amount of HLA antigens was quantitated by inhibition of
lymphocytotoxicity (LCT) and by enzyme-linked immunosorbent assay (ELISA) using operationally monospecific
polyclonal HLA antibodies or murine HLA-specific monoclonal antibodies, respectively. We found that in 11 out of
13 HLA-A2 and in 9 out of 10 HLA-B13 experiments, platelets from antigen-negative donors pretreated with plasma
from the same number of antigen-positive donors inhibited LCT to the same extent as platelets from antigen-positive
donors. Nevertheless, the in vitro adsorbed HLA antigens onto antigen-negative platelets were, unlike those on
antigen-positive platelets or in plasma, not reactive with monoclonal antibodies as quantitated by ELISA. Similarly,
infusion of HLA-A2-negative platelets from single donors into 3 HLA-A2-positive, thrombocytopenic patients with
bone marrow failure led to a good platelet increment, but did not convert the HLA type of donor platelets, neither at
2 h nor at 18 h posttransfusion. On the basis of these results, we conclude that soluble HLA antigens can be taken up
by human platelets from plasma in small amounts. However, the major portion of HLA antigens appears to be
integral membrane constituents.
Background: The clinical impact of HLA-DR alloantibodies in renal transplantation is still controversial. This may be partly due to the lack of specificity and sensitivity of current detection methods, e.g. complement-dependent cytotoxicity test employing B lymphocytes as target antigens. Patients and Methods: In this study, we analyzed the incidence and specificity of HLA-DR antibodies after renal transplantation by use of the antigen-specific capture assay MAILA. 53 primary cadaver kidney recipients were recruited for a prospective study and were retrospectively assigned to the following groups: 20 patients with unsuspicious clinical course within the first 3 months after transplantation (control group), 20 patients undergoing histologically proven acute rejection within the first 3 months after transplantation, and 13 patients with chronic rejection 1 year or later after transplantation. 105 patients’ sera collected prospectively were analyzed by MAILA using 13 homozygous B-lymphoblastoid cell lines (B-LCL) carrying the common HLA-DR specificities. Results: In the control group, only 1 of 19 patients (5.3%) without acute rejection revealed HLA-DR antibodies after transplantation. In contrast, HLA-DR alloantibodies could be detected post transplant in 36.8% (7/19) and 69.2% (9/13) of patients with acute and chronic rejection, respectively. The frequency of HLA-DR antibodies present in both study groups was significantly higher in comparison to the control group. Of the 17 patients who received a graft across a donor recipient HLA-DR mismatch, 5 patients exhibited donor-specific alloantibodies. However, the majority of antibodies detected was not specific for mismatched HLA-DR alloantigens. Conclusion: HLA-DR antibodies were significantly associated with transplant rejection in first cadaver renal transplantation, especially in patients undergoing chronic rejection. Although donor specificity was not observed in the majority of patients, monitoring of HLA-DR antibodies might support diagnosis of graft rejection.
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