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At least 775 records · Page 43Linked to original sources
PubMed1987

Is serum the optimal source for HLA antibodies?

The cytotoxic reactivity of 18 predefined class I HLA serum antibodies was compared with that of antibody preparations containing anticoagulants. ACD-A, EDTA, 4% citrate and heparin plasmas all showed lower cytotoxicity than serum antibodies. Recalcification of both platelet-rich and platelet-poor ACD-A plasma did not fully restore the antibody reactivity, suggesting a detrimental effect of calcium chelation. This effect was exclusive of volume or of any platelet or plasma protein involvement. The changes in pH contributed to the lower reactivity and to the increased lympholytic effect, whereas adjusting the pH toward the serum value improved the reactivity. Heat-inactivated antibodies showed only a slightly reduced cytotoxicity. Heparin had the least effect of all anticoagulants on the reactivity, although in heparin there was a definite dose-dependent decline in cytotoxic titer which was probably related to anticomplementary activity. Calcium chelators, such as EDTA and citrate, showed marked cytotoxic inhibition at half the usual complement concentration. This effect was more pronounced when the anticoagulant and lymphocytes were incubated prior to cytotoxicity testing. At the complement concentrations used, the inhibitory effects of the citrate anticoagulants appeared to be primarily calcium-related. Inhibition tests, serial titrations and testing of varying calcium concentrations confirmed the superiority of serum as antibody source.

Anticoagulants↗
PubMed2006

Transplant tolerance in non-human primates: progress, current challenges and unmet needs.

Given the significant morbidity associated with current post-transplant immunosuppressive regimens, induction of immune tolerance continues to be an important goal of clinical organ transplantation. While many strategies for inducing tolerance have been successfully applied in murine models, significant barriers are faced when translating these approaches to the clinic. This has necessitated pre-clinical studies in the more closely related model system, the non-human primates (NHP). In this review, we will discuss the four most prominent strategies for inducing transplantation tolerance and highlight their relative success and shortcomings in NHP. These strategies are: (1) T-cell costimulation blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance induction through regulatory T-cells. After discussing the progress that has been made with each of these strategies, we will identify this field's most pressing unmet needs and discuss how we may best overcome the resulting barriers to tolerance induction.

Animals↗
PubMed1980

Human leucocyte antigens A, B, C, and DRW in idiopathic "warm" autoimmune haemolytic anaemia.

Twenty patients with idiopathic "warm" autoimmune haemolytic anaemia and 40 controls were types concurrently for human leucocyte antigens (HLA) A, B, C, and DRW. There was a significantly stronger association of HLA-B8 with the disease (chi 2 = 10.39; p = 0.018) than HLA-DRW3 (chi 2 = 3.71; P = 0.35) and the patients also showed a significant increase in BW6 homozygosity (chi 2 = 7.13; P = 0.01) and a corresponding reduction in BW4 (chi 2 = 7.13; P = 0.02). (All p values corrected for number of antigens at each locus.) These findings suggest that susceptibility to idiopathic autoimmune haemolytic anaemia is associated more closely with the HLA-B locus than with DRW3.

Adult↗
PubMed2001

HLA typing.

Explore the source record for details and available documents.

Cytotoxicity Tests, Immunologic↗
PubMed2003

Extending preimplantation genetic diagnosis: medical and non-medical uses.

New uses of preimplantation genetic diagnosis (PGD) to screen embryos prior to transfer raise ethical, legal, and policy issues that deserve close attention. Extensions for medical purposes, such as to identify susceptibility genes, late onset disease, and human leukocyte antigen (HLA) matching, are usually ethically acceptable. Whether embryo screening for gender, perfect pitch, or other non-medical characteristics are also acceptable depends upon the parental needs served and the harm posed to embryos, children, and society. Speculations about potential future uses of PGD should not prevent otherwise acceptable current uses of PGD.

Age of Onset↗
PubMed2003

Bach to the future: response to: Extending preimplantation genetic diagnosis: medical and non-medical uses.

Professor Robertson sketches an elegant framework for policy evaluation and regulation of the use of preimplantation genetic diagnosis for various medical, medical related, and non-medical purposes. In criticism of his position, I argue that the distinction between policy and ethics upon which his argument relies is highly unstable, and the approach taken to ethical evaluation of particular parental interests leaves open many issues which the policy approach would hope to exclude. In conclusion I argue that while his position ultimately fails, the onus is on his critics to come up with a viable and satisfying alternative.

Attitude to Health↗
PubMed1975

Detection of platelet isoantibodies by (3H)serotonin platelet release and its clinical application to the problem of platelet matching.

The detection of platelet isoantibodies by the release of (3H)serotonin from platelets has been evaluated. The conditions for optimal release of (3H)serotonin with platelet isoantibodies using a microtechnique have been defined. A group of cardiac surgery patients were followed pre- and post-transfusions, with 48percent developing a positive serotonin release assay. Of these patients, 16percent also had a platelet complement-fixing and/or lymphocytotoxic isoantibody. There was variation in the degree of correlation between (3H)serotonin release and lymphocytotoxicity using individual National Institutes of Health typing serum. The matching obtained between family members by both techniques showed a close correlation when each technique was evaluated separately using the same NIH typing serum. The detection of iso-antibodies in patients with hematological malignancies correlated with the unresponsiveness to unmatched platelet transfusions in 15 out of 17 cases. The use of the patient's isoantibody to matched platelets of family members by (3H)serotonin release correlated well with the clinical response to transfusion with these platelets. The data suggest that (a) platelet isoantibodies can be detected with increased frequency by (3H)serotonin release; (b) (3H)serotonin release is a specific reaction depending on the surface antigen of the platelet; and (c) the method can be used to match compatible family members for platelet transfusions.

Blood Donors↗
PubMed1991

Autoreactive lymphocytotoxic IgM antibodies in highly sensitized dialysis patients waiting for a kidney transplant: identification and clinical relevance.

The contribution of different families of lymphocytotoxic antibodies in the serologic reactivity of 45 highly sensitized dialysis patients (HSDP) (panel reactivity antibody value-PRA greater than 80%) was assessed by analyzing patients' sera for the presence of auto- and alloreactive IgM and alloreactive IgG antibodies. A total of 220 sera was screened at different incubation temperatures, before and after treatment with the reducing agent dithiothreitol, against a large variety of cell targets by means of complement dependent cytotoxicity (CDC) and antiglobulin augmented (AHG) CDC assays. The results allowed to subdivide the HSDP under study into four groups: Group 1 consisted of 13 untransplanted patients and 14 patients with a prior failed graft whose PRA values did not change following DTT treatment. Alloreactive IgG antibodies alone, with anti-HLA specificity, were present in the sera of this patient group. Group 2 consisted of 3 untransplanted patients whose sera did not contain any autolymphocytotoxic antibody but appeared completely unreactive to panel lymphocytes following DTT treatment, thus confirming the presence of alloreactive IgM only endowed with antiHLA reactivity. Group 3 consisted of 4 untransplanted and 4 patients with a prior failed graft whose sera were found to contain in addition to autoreactive IgM also alloreactive IgG antibodies. Their PRA values declined after DTT treatment on average from 96.2% to 45% and from 95% to 52.5%, respectively. Group 4 consisted of 6 untransplanted patients whose PRA reactivity to both autologous and panel lymphocytes completely disappeared following DTT treatment, thus indicating that their sera contained exclusively autolymphocytotoxic IgM antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Immunogenetics of the human major histocompatibility complex.

The biologic significance of the human major histocompatibility complex (MHC), also referred to as HLA, is well known through its influence on transplant immunity and its association with many diseases. This article attempts to summarize recent progress in the field of HLA polymorphisms. Topics discussed include the genetic basis of HLA, methods to determine HLA polymorphisms, and definitions of HLA Class I and II polymorphisms.

Genes, MHC Class I↗
PubMed1991

Clinical relevance of antibodies to non-HLA antigens in organ transplantation.

This article summarizes work that focuses on alloantibodies that bind to endothelial cells and attempts to provide an evaluation of the apparent role that antigens distinct from classic HLA alleles, and not expressed in lymphocytes, may play in kidney transplant rejection. The most recent experience with the donor-skin crossmatch in prediction of early kidney allograft rejection also is described.

Endothelium, Vascular↗