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Immunobiological determinants in organ transplantation.

The most important development in determining successful organ transplantation has been the improved understanding of the immune response and the interactions between antigens, antibody, immune complexes, complement component, lymphocytes and macrophages. The initiation and termination of an immune response, whether cellular or humoral depends upon cellular interaction between subsets of the lymphocyte cell series and macrophages. An equilibrium between helper and suppressor T cells determines protection of the host from non-self tissue invasion, infection and neoplasia. The role of mediators, immunosuppressants, hybridomas and recombitant DNA technology are briefly considered. The relative importance of tissue typing and blood transfusion in preventing allograft rejection is considered and the role of immunological monitoring in allograft transplantation is reviewed.

B-Lymphocytes↗

Studies on the antigenicity of bone. II. Donor-specific anti-HLA antibodies in human recipients of freeze-dried allografts.

UNLABELLED: Freeze-dried bone allografts from donors of known tissue type evoked donor-specific anti-HLA antibodies in nine of forty-three patients (forty-four procedures). Eight of the nine sensitized patients were followed roentgenographically for an average of twenty-three months and were known to have had a satisfactory resolution of the benign process for which the graft was employed. The ninth patient was doing well when lost to follow-up four months after receiving a bone allograft. CLINICAL RELEVANCE: The questions of whether immune responses to bone allografts occur in humans and, if so, adversely influence the incorporation of the graft can be answered at this time only by demonstrating the presence and frequency of such responses and how they correlate with clinical events. A large variety of techniques can be used to demonstrate immune responses. The technique that we used revealed that a small group of patients became sensitized to HLA antigens that were known to be present in the allograft donor but none of the recipients had evidence of adverse effects caused by the graft, as judged non-invasively.

Adolescent↗

An enzyme-linked immunosorbent assay for platelet compatibility testing.

The selection of platelet donors for patients who are refractory to random donor platelets often presents a difficult clinical problem. We describe an enzyme-linked immunosorbent assay (ELISA) for evaluating alloantibodies in refractory patients. Platelets from prospective donors are immobilized on microtiter plates and, after incubation with test serum and washing, platelet-bound IgG is detected with enzyme-linked anti-human IgG. Platelets from 46 prospective donors were tested. Twenty-two were judged compatible (reciprocal of the antibody titer less than 16) and, of these, 15 were used as platelet donors; each gave a measurable platelet increment after transfusion. The magnitude of the response was roughly proportional to the assay results. Platelets from donors giving antibody titers less than 4 resulted in platelet increments at 1 hr ranging from 4,890 to 22,200 (median 12,600), while platelets from donors giving titers of 8 or 16 resulted in lesser increments (550-4548). Conversely, 5 of the 24 patients found incompatible by the assay (titer greater than 16) gave no platelet increment, and in 3 instances, the recipient developed fever and chills after the transfusion. The assay is sensitive, simple, and adaptable to the clinical laboratory. Platelets from volunteer donor panels can be plated and stored for up to 6 mo.

Blood Platelets↗

[Practical interest of a micromethod for neuraminidase treatment of lymphocytes in transplantation immunology (author's transl)].

Vibrio cholerae neuraminidase treatment increases the cell sensitivity to complement and antibodies cytotoxic action. This property can be applied to the microlymphocytotoxicity technic for antibodies study in dialysed and kidney transplanted patients and for pretransplantation cross-matches. The enzymatic treatment usually employed needs a great deal of lymphocytes submitted in a second step to antibodies cytotoxic action. But this method appeared difficult to be routinely applied. We developed a simpler method consisting in treating only the lymphocytes needed to perform the test, on the reaction plate itself. This method gives the same results as the classical enzymatic treatment: the intensity of the weakly positive reaction is strongly increased, after pretreatment of cells; in certain cases, it allows one to detect cytotoxic antibodies not revealed without neuraminidase. These antibodies can be related (or not) to HLA system but practically the more important fact is the ability of this method to reveal an eventual incompatibility.

Antibodies↗

Residual clonable host cell detection for predicting engraftment of T cell depleted BMTs.

Rejection of T-depleted BMTs is predominantly mediated by alloreactive host T cells. A low but significant number of radiochemoresistant clonable T cells can be detected following a conventional cytoreductive protocol given prior to T-depleted BMT. Elimination of these cells increases the engraftment rate. We found no clonable T cells at the end of the conditioning regimen in 100 ml of peripheral blood from 47 patients who received an HLA-identical T-depleted BMT. None rejected the graft and none displayed mixed chimerism. In addition, although no clonable T cells were detected in nine patients who received a mismatched BMT, two rejected their graft. However, in three mismatched patients, who for clinical reasons received a modified pre-BMT schedule, the presence of host clonable T cells was associated with immunological rejection. These findings suggest that the detection of clonable T cells should prove a valuable indicator for optimising immunosuppression prior to T-depleted BMT.

Adolescent↗

An MHC (HLA-A, -B, C2, BF, HLA-DR, GLO1) haplotype study of 497 Danish normal families with 1970 children including 97 twin pairs.

Extended MHC haplotypes comprising HLA-A, -B, -DR, C2, BF and GLO1 loci observed in the parents of 497 Danish normal families are presented, with particular regard to the haplotypes that include BF variants or the C2*2 allele. The known association of HLA-B35, -DR1 with both -A3 and -A11 appeared to depend upon the BF type: HLA-B35, BF*S, -DR1 is strongly associated with -A11, whereas -B35,BF*F,-DR1 is strongly associated with -A3. Further, in the present material DZ twins of the same sex shared HLA-haplotypes more often than did twin pairs of different sex.

Denmark↗