Alan Ting

Alloimmunisation to HLA antigens following transfusion with leucocyte-poor and purified platelet suspensions.

24 previously non‐transfused patients were given three transfusions of 200 times 108 platelets at 14‐day intervals. Group I (12 patients) received leucocyte‐poor platelet suspensions with a mean contamination of 15 times 106 leucocytes per transfusion. Group II (12 patients) received platelets with <5 times 106 leucocytes per transfusion. 5 patients in group I and no patients in group II developed lymphocytotoxic antibodies (p == 0.037). Platelets with fewer than 5 times 106 leucocytes did not seem to stimulate a response to major histocompatibility antigens, but with a small contaminating dose of leucocytes appeared to be highly immunogenic.

Ulcerative colitis and HLA phenotype.

The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.

Studies of HLA-DR with Relevance to Renal Transplantation*

The serological determination of leukocyte antigens in man which began some 20 years ago, and their subsequent recognition as histocompatibility antigens, led to immediate interest in the possible application of leukocyte typing for matching of donors and recipients of organ grafts. As the genetic control of these antigens gradually was elucidated, it was apparent that the antigens detected in the late sixties could be divided into two series of allelic antigens. The two series of the major histocompatibility complex (MHC) in man, first designated HL-A, but later to become HLA, were shown to be genetically controlled by two loci on chromosome 6. Over the next 10 years extensive studies of matching for HLA, both in living related and in cadaver transplantation, were performed in an attempt to improve the success of renal transplantation. There is no question that within a family genotyping for HLA allows a precise determination of HLA identity, or otherwise, of the potential donor and recipient. Furthermore the outcome of intrafamilial renal allografts is very much in accord with the genetic disparity in HLA between donor and recipient. However, in cadaver renal transplantation after initial encouraging reports of a correlation between matching for a limited number of HLA antigens and cadaveric graft outcome (Morris et al. 1968, Patel et al. 1968) reports began to appear showing little or no correlation, especially from the pioneer laboratory in the field, that of Terasaki (Mickey et al. 1971). Controversy about the role of matching for HLA-A,B in cadaver transplantation raged over the next 8 years or so, but by the mid-seventies some degree of consensus was reached, namely that grafts well matched for HLA-A,B showed about a 10-20% better graft survival at I year than poorly matched grafts. (Morris et al. 1978a).

A monoclonal antibody recognizing hla-dr2 on malignant and activated cells.

A monoclonal antibody, designated NDS15.38, which recognizes a polymorphic determinant of HLA-DR, was produced from a fusion in which mice were immunized with the human B lymphoblastoid cell line GIR2 (HLA type A1, B8, 27, Cw2, DR2, 7). NDS15.38 functions efficiently as an affinity column and purifies a two-chain complex of molecular weight 33 000 and 30 000 under reducing conditions. The monoclonal antibody reacts with HLA-DR2-positive B lymphoblastoid cell lines and B lymphocytes from patients with chronic lymphatic leukemia in an indirect radioactive binding assay. However, NDS15.38 does not appear to react with peripheral blood B lymphocytes from normal individuals. Using a peroxidase staining technique, NDS15.38 was shown to react with phytohemagglutin (PHA)-stimulated lymphocytes and with apparently activated B cells in the germinal centers of lymph nodes from individuals who were tissue typed as HLA-DR2. Thus it appears that NDS15.38 recognizes a polymorphic determinant of HLA-DR on malignant and stimulated cells, but not on resting cells.

HLA-DR and Renal Transplantation

The serological detection of leukocyte antigens in man began some 20 years ago. Their subsequent recognition as histocompatibility antigens led to immediate interest in the possible application of leukocyte typing and matching to improve renal allograft survival. In the late 1960s it became apparent that these leukocyte antigens could be grouped into two series of allelic antigens. The two series of the major histocompatibility complex (MHC) in man (designated HLA-A and -B) were shown to be genetically controlled by two loci on chromosome 6.

HLA in Transplantation

Transplantation is associated with a number of iatrogenic complications and therefore it is perhaps not unreasonable for a discussion on HLA in transplantation to be included in the HLA and Disease Symposium. We propose to discuss some aspects of the current role of matching for HLA in renal transplantation, the increased expression of Class II antigen during rejection episodes in renal transplants, the transfusion effect as observed in man with some experimental data which would provide a role for the MHC in the phenomenon, and finally say something about possible mechanisms of the transfusion effect.