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Results for “Histocompatibility Testing”

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PubMed1976

Successful kidney trasnplant in patient with positive crossmatch due to autoantibodies.

Prior to kidney transplantation a young woman was found to have lymphocytotoxic antibodies to an HLA/mixed lymphocyte culture identical sib donor. The serum killed 75% of the lymphocytes at 22 C but was unreactive at 37 C. At room temperature it was cytotoxic for many lymphocytes of a random panel and also reacted with the recipient's own cells. Complement was required for cytotoxicity. Absorption with lymphocytes but not with platelets abolished the reaction. The antibodies disappeared spontaneously and the transplant was performed. There was no evidence of rejection and at 6 months the kidney is in excellent condition. Cold-reactive lymphocyte specific autoantibodies causing a positive crossmatch could be distinguished from anti-HLA antibodies and did not preclude a successful kidney transplant.

Absorption↗
PubMed1979

Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy.

The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.

Animals↗
PubMed1982

Adverse effect of pretransplant blood transfusions on survival of matched kidney allografts in dogs.

Previous studies from our laboratory have already shown that pretransplant blood transfusions from third-party donors significantly prolong kidney allograft survival in mismatched unrelated immunosuppressed dogs. In the present study, a similar effect was found in related donor-recipient pairs mismatched for two haplotypes (P less than 0.05); no significant effect was observed in one-haplotype-mismatched combinations (P = 0.34). Pretransplant blood transfusions did not have a beneficial influence on kidney allograft survival in immunosuppressed DLA-identical, related donor recipient pairs. After withdrawal of immunosuppressive therapy, transfused dogs in this group rejected their kidneys even more frequently than did nontransfused dogs (P = 0.16). A comparable undesired effect of blood transfusions was found for recipients of unrelated kidneys which were identical with respect to DLA-A, B, and D: transfused recipients of those kidneys rejected the graft significantly more often than the untransfused controls (P less than 0.01). The most likely explanation for this adverse effect is that blood transfusions given to the recipient may cause crossimmunization for undefined, probably minor, antigens of the donor kidney. Apparently, differences arising from these minor histocompatibility antigens become manifest only after withdrawal of the immunosuppressive therapy. Furthermore, it appeared that the effect of histocompatibility matching on kidney allograft survival is less for transfused than for untransfused dogs. The most important conclusion is, however, that the beneficial effect of blood transfusions appears to be dependent on the degree of matching: while blood transfusions are on the whole beneficial for unmatched kidneys, they are likely to have no effect, or even to be harmful, for matched kidneys.

Animals↗
PubMed1984

The new recombinant haplotypes r19 and r20 in RT1, the MHC of the rat.

Two new recombinants, designated r19 and r20, have been found in RT1, the rat major histocompatibility complex. In both recombinants the A and I regions appear to be derived from one parental haplotype, and a further region, able to induce both skin graft rejection and cytotoxic lymphocytes is derived from the other. The properties of this region appear similar to the previously described RT1C and the putative genotypes of the PVG X R19 and PVG X R20 congenic lines are therefore AaIaCc and AcIcCa, respectively. Evidence suggesting that the two recombinants may not be reciprocal is discussed.

Animals↗
PubMed1986

Characteristics and clinical relevance of autolymphocytotoxins in patients with aplastic anemia.

Serum of 68 patients with aplastic anemia was tested for the presence of autolymphocytotoxins (auto-LTs). Prior to specific disease treatment, 16 patients (24%) displayed antibodies cytotoxic to their own lymphocytes. These antibodies had the characteristics of cold-reactive lymphocytotoxins. Their detection in patients' sera was found unrelated to a viral or toxic cause of the disease or the patients' HLA genotype. Broadly reactive anti-HLA antibodies were less frequent in pretreatment sera containing auto-LTs, suggesting that these autoantibodies could modulate alloantibody production. However, after specific disease treatment, the alloantibody frequency was comparable in patients with or without auto-LTs. We found no significant difference in response to antilymphocyte serum or bone marrow graft outcome in the patients in relation to the presence or absence of pretreatment auto-LTs. This observation suggests that the detection of these autoantibodies in aplastic anemia has no clinical relevance.

Adolescent↗
PubMed1989

Successful transplantation after conversion of a positive crossmatch to negative by dissociation of IgM antibody.

Preliminary crossmatching usually eliminates highly sensitized patients from consideration for renal transplantation. However, if the crossmatch is positive because of the presence of IgM antibody, this activity can be eliminated by treatment with the reducing agent Dithiothreitol (DTT). Successful transplantation may then be possible in patients whose crossmatch is positive due to the presence of IgM antibody. After treatment with DTT, the sera of 25 highly sensitized patients were measured for cytotoxicity against a selected panel of 40 cells. Those whose high %PRA could be attributed to blood transfusions or previous transplants did not change with DTT. Only two patients who had developed high panel reactivity, without a clear cause, had little reactivity remaining after DTT treatment of their sera. To select patients whose crossmatch might be rendered negative by DTT treatment, we developed a "minipanel" screening protocol. Patients whose monthly PRA cells increased greater than 30% from baseline had their serum samples treated with DTT to reduce IgM. The treated sera were tested against a panel of six cells. If there was little or no cytotoxicity, it was assumed that IgM antibody was responsible for the positive crossmatches. All subsequent cadaver donor crossmatches were done with and without DTT treated sera. Five patients (2 living-related; 3 cadaver) with current crossmatches positive before, but negative after, DTT treatment continue to have functioning kidneys 3-15 months after renal transplantation. There were no hyperacute rejections. We conclude that patients with IgM antibody can be successfully transplanted if they have a negative cross-match after reduction of IgM antibody in their serum samples. A "minipanel" helps to identify patients who will benefit from DTT treatment.

Adult↗
PubMed1989

Contributions and clinical significance of IgM and autoantibodies in highly sensitized renal allograft recipients.

The contributions of auto and IgM antibodies in the levels of serologic reactivities of 30 highly sensitized patients were assessed by autologous T cell crossmatches at 4 degrees C and 22 degrees C and dithiothreitol (DTT) reduction of IgM antibodies. The range of panel reactivities of sera from these patients was 30-100%, median 55%. A monthly screen of these sera against a 30-member T cell panel was performed with and without addition of DTT (final concentration = 0.005 M). The results were divided into 3 groups. Group 1 consisted of 17 sera whose PRA values did not change following the DTT treatment. Also none of these sera had autoantibodies, suggesting that these sera contained DTT-resistant (IgG) antibodies, most likely directed against allogeneic targets. Group 2 consisted of 10 sera whose PRA values declined substantially (20-42%) following the DTT treatment, but only 1 serum derived from a patient with systemic lupus erythematosus had autoantibodies. These results suggested that although these sera contained IgM and IgG antibodies, these antibodies were most likely directed at allogeneic target structures with only one exception. Group 3 consisted of 3 sera that became completely unreactive to panel lymphocytes following the DTT treatment. All 3 sera had autoantibodies that were also removed with DTT, suggesting that these sera contained predominantly IgM antibodies directed at autologous target cells. All 3 patients from whom these sera were derived received successful kidney transplants across donor-specific positive T cell crossmatches that became negative following the DTT treatment. We conclude that although 13 out of 30 patients have IgM antibodies, only a small subset of these patients have autoantibodies. Renal transplantation in the presence of auto/IgM antibodies may be safe.

Antilymphocyte Serum↗
PubMed1999

Spontaneous acceptance or rejection of orthotopic liver transplants in outbred and partially inbred miniature swine.

BACKGROUND: Results of clinical liver transplantation have shown that rejection and loss of human liver allografts occurs despite immunosuppression. Because genetic disparity and liver immunogenicity remain a matter of controversy, we reexamined the fate of outbred liver allografts without immunosuppression and used partially inbred miniature swine, in which the genetics of major histocompatibility complex (MHC) antigens have been characterized and can be controlled. METHODS: Orthotopic liver transplantation was performed between pairs of outbred domestic farm pigs and between pairs of inbred miniature swine with genetically defined major histocompatibility (SLA) loci. A passive splenic and vena caval to jugular vein shunt with systemic heparinization prevented hypotension during the anhepatic phase. Immunological responses were monitored by mixed lymphocyte culture (MLC), CML, skin graft rejection, liver biopsies, and serial serum chemistries. RESULTS: Median survival of technically successful liver allografts between pairs of outbred pigs (n=20) was 38 days and between partially inbred swine matched at the SLA locus (n=17) was 79 days. MLC responsiveness did not correlate with the development of rejection. Five of 20 (25%) outbred pigs and 6 of 17 (35%) MHC matched inbred miniature swine survived more than 100 days. In the long-term survivors, donor, but not third party, MHC matched skin graft survival times were prolonged. In contrast, all SLA-mismatched inbred recipients (n=26) died rapidly from massive liver rejection, with a median survival time of 9 days. In these rejecting animals, the marked MLC responsiveness to donor lymphocytes evident pretransplant diminished rapidly after transplantation, but an undiminished PHA responsiveness and a blunted third party MLC response persisted. CONCLUSION: The length of survival and the degree and incidence of rejection were similar in outbred pigs and in SLA-matched inbred miniature pigs, indicating that the outbred animals were, therefore, probably closely related and shared relevant genes. However, survival was significantly shortened and liver allograft rejection was accelerated in SLA-mismatched inbred swine. These results indicate that major histocompatibility differences play an important role in the rejection of liver allografts, as is true for other vascularized grafts in the unimmunosuppressed recipient. The development of liver allograft rejection across non-MHC differences is variable and, when present, appears to be a chronic process.

Animals↗