HLA-B*9553: a novel HLA allele shown in three generations of a family.

Human leukocyte antigen (HLA)-B*9553, a novel HLA-B allele, was identified in a volunteer hematopoietic stem cell donor. HLA-B*9553 differs from the closely related allele HLA-B*1518 in one single nucleotide substitution resulting in an amino acid substitution.

Neutropenia and anaemia due to carbimazole-dependent antibodies.

Carbimazole-dependent antibodies to erythrocytes were detected in the sera of three anaemic patients who had been treated with carbimazole for hyperthyroidism. By the use of Rhnull-typed erythrocytes, we could show that some of these were directed against the proteins of the Rh complex. Carbimazole-dependent antibodies eluted from erythrocytes showed no binding to other blood cells. One patient also presented with neutropenia and mild thrombocytopenia. Additional carbimazole-dependent antibodies against the neutrophil-specific Fcgamma receptor IIIb (FcgammaRIIIb, CD16b) and the broadly expressed platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) were detected in this patient's serum. Surprisingly, the PECAM-1-reactive drug-dependent antibodies were also detectable in the sera of the other two patients with normal leucocyte and platelet counts. We assume that carbimazole can induce cell lineage-specific drug-dependent antibodies that cause cytopenia and also drug-dependent antibodies against the broadly expressed PECAM-1 molecule that may cause mild but not severe cytopenia.

[Detection of drug-induced antibodies to erythrocytes in the gel test]. / Nachweis medikamentenabhängiger Antikörper gegen Erythrozyten im Geltest.

Drug-induced immune hemolytic anemia is a serious hematological disorder which results from increased red blood cell destruction due to the production of autoantibodies, drug (metabolite)-dependent antibodies (DDAb) or both types of antibodies, even in one patient by the same drug. One of the major problems related to DDAb is that the causative drug (metabolite) usually does not bind tightly to target cells, and the antibodies are completely removed from the cells by conventional washing procedures, i.e. by the antiglobulin test. We have recently shown that the microtube geltest, by which the antiglobulin test is performed without washing the cells, is a highly sensitive and reliable alternative method for the detection of all kinds of DDAb. The results obtained with different DDAb are discussed.

Pretreatment of rat pancreatic islets with MHC I-A monoclonal antibody: in-vitro and in-vivo effects on islet antigenicity.

Pancreatic islet allografts are rejected very rapidly due to their high immunogenicity. Several attempts have been made to reduce the immunogenicity prior to transplantation. We treated islets with MHC Ia (class II) antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. This treatment caused a distinct reduction of Ia antigen positive cells, which was demonstrated by indirect immunofluorescence tests. A total depletion of the Ia antigens, however, could not be achieved. As a second in-vitro test to evaluate the effect of the antibody treatment a mixed lymphocyte islet culture (MLIC) was performed. The partial Ia antigen reduction provoked a significantly reduced but not completely suppressed allogenic T-cell response. Antibody treatment did neither impair the morphological integrity nor the function of the islets as could be demonstrated by syngenic transplantation of islets pretreated by antibodies in the same way. After allotransplantation of antibody-pretreated islets across a major histocompatibility barrier into non immunosuppressed rats, however, there was no significant prolongation of the graft survival. Thus, a partial reduction of the number of the Ia antigen positive cells within the islets is not sufficient for the prevention of allograft rejection.