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PubMed1978

Effect of prior third-party blood transfusions on canine renal allograft survival.

The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed. Genetic control of this reactivity or a linkage of this property to DLA, sex, or red blood cell markers inheritance was not apparent in the four beagle families studied. The two recipients with the lowest immune reactivity scores were also found to be the longest survivors after a DLA-mismatched kidney graft. Seven other recipients with higher scores rejected their DLA-mismatched kidneys as rapidly as did untransfused animals. Kidney graft survival was decreased in some recipients of DLA-identical kidneys (n = 5), presumably through sensitization for minor histocompatibility antigens. A normal or an increased survival time of DLA-identical kidneys was found in the remaining animals (n = 6). The majority of these recipients appeared to have a higher than average reactivity in two-stage microcytotoxicity testing. This might have been attributable to the presence of enhancing antibodies. Further studies in preclinical animal models are needed to define the optimal transfusion policy for human patients awaiting a kidney graft.

Animals↗
PubMed2026

Two Genomes, one Outcome: Stratifying Donor and Recipient Polygenic Risk Score to Improve Kidney Allograft Longevity.

Kidney transplantation outcomes arise from complex interactions among donor organ quality, recipient susceptibility, and immunologic compatibility, yet conventional clinical risk models explain only a modest fraction of outcome variability. Polygenic risk scores (PRS) offer a promising framework to enhance transplant risk assessment by integrating genome-wide genetic information from both donor and recipient into biologically informed models. This narrative review examines the mechanistic basis for PRS application in kidney transplantation and variant clustering approaches that link polygenic signals to specific biological pathways underlying alloimmunity, fibrosis, and metabolic dysfunction. We compare current PRS construction methodologies, highlighting their respective strengths and limitations in transplant cohorts. Transplant PRS are distinguished from single-genome disease models by their capacity to capture dual-genome interactions, simultaneously quantifying inherited donor organ liability and recipient genetic susceptibility within an integrated framework. This dual-genome architecture requires novel risk stratification paradigms in which combined donor-recipient polygenic profiles inform pretransplant decision-making in ways that neither genome alone can achieve. However, current PRS contribute only incremental variance beyond established clinical predictors, and critical limitations persist, including European ancestry bias, small cohort sizes, incomplete replication, and undefined clinical actionability thresholds. We critically evaluate these implementation barriers and outline future directions for integrating dual-genome PRS with clinical, molecular, and environmental data. The longer-term goal is to advance precision kidney transplantation through applications such as donor selection, immunosuppression tailoring, and individualized posttransplant surveillance. Realizing this potential will require validation in adequately powered, ancestry diverse, prospective transplant cohorts.

Journal Article↗
PubMed1976

Dialyzable transfer factor in the treatment of human osteosarcoma: an analytic review.

In conclusion, then, we would answer the seven questions raised earlier concerning transfer factor as follows: Certianly, as shown by clinical results, it does exist. It does have a definite immunologic effect in humans, boosting cell-mediated immunity, as shown by a rise in the level of active T cells. Its clinical effects have been demonstrated repeatedly, and it should become useful in still other clinical situations as further research provides more effective therapeutic modalities. Transfer factor from selected donors appears to provide prophylaxis against metastasis when administered to osteosarcoma patients with no clinically evident metastases at the time of surgical removal of the primary tumor; whether this treatment is superior to chemotherapeutic prophylaxis is conjectural and controversial. Its mechanism of action has not been demonstrated as yet, although many theories exist. The best evidence is that the effects are both specific and nonspecific. It appears to be produced by T lymphocytes. The exact nature of the substance we call "transfer factor" remains to be elucidated. Further research should provide more conclusive answers to these questions.

Animals↗
PubMed2026

Age- and sex-adjusted genomic differences between Korean and Beat AML cohorts.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Journal Article↗
PubMedDate not supplied

Protecting chicks and poults from Salmonellae by oral administration of "normal" gut microflora.

Resistance of young chicks and poults to salmonella exposure was substantially increased by early oral administration of intestinal contents or feces from selected adult chickens. Protection was secured also by administering anaerobic broth cultures of intestinal microflora from selected donor birds. Protection, was substantial for 63 days, the longest period tested, although it could be overcome by severe exposure. The protective mechanism appears to be a consequence of competitive exclusion of salmonella by "normal" microflora of the gastrointestinal tract.

Administration, Oral↗
PubMed1978

Successful use of multiagent immunosuppression in the bone marrow transplantation of sensitized patients.

Of 23 patients with severe aplastic anemia, 17 were sensitized to histocompatibility antigens of HLA-A, -B, and -D loci-identical potential sibling donors as determined by cell-mediated lysis (CML) assays in vitro. Antibody-dependent sensitization was detected in 3 patients, antibody-independent cellular sensitization in 11, and both in 3. Fourteen sensitized patients were transplanted after initial multiagent immunosuppression consisting of rabbit anti-human thymocyte serum, procarbazine, and cyclophosphamide, eleven with a CML-positive donor and three with a CML-negative donor. Engraftment was achieved in each of 13 patients who were evaluable, and only 2 ultimately rejected their marrow grafts, 1 with subsequent return of his own marrow function. Five patients without evidence in vitro of sensitization were transplanted after immunosuppression with cyclophosphamide alone; none of these rejected their grafts. These studies show that sensitized bone marrow transplant recipients can be successfully transplanted after optimal donor selection and multiagent immunosuppression.

Adolescent↗
PubMed1979

[Sperma- and HLA-antibody demonstration in sterility].

Sperma antibodies were detected by means of passive haemagglutination, the immobilisation test and immunofluorescence in the serum of 16 females from among 150 infertile married couples. These serums (experimental group) and 16 serum samples containing no sperma antibodies (control group) were investigated for the presence of cytotoxic HLA-antibodies against lymphocytes from their married partners and from 20 selected donors by means of the micro-lymphocyte toxicity test. HLA-antibodies against the lymphocytes of the husbands involved were found in four women from the experimental group. Two of these four serums also reacted with 20% of the test lymphocytes. In the control group, lymphocyte-toxic antibodies against test subjects were also found in all three serums which cross-reacted with the lymphocytes of the husbands. No new diagnostic or therapeutic criteria for the treatment of sterility can be derived from the combined humoral sperma and cytotoxic HLA-antibodies in the serum.

Antibodies↗
PubMed1977

Treatment of Bechçet's syndrome with transfer factor.

Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.

Adult↗
PubMed1975

An in vitro method for study of human lymphocyte cytotoxicity against mumps-virus-infected target cells.

A chromium release assay was used to study lymphocyte-mediated cytotoxicity against mumps virus-infected target cells in vitro. Purified lmyphocytes from randomly selected donors killed significantly more virus-infected Vero cells than non-infected cells. Lymphocyte-target cell ratios of 50 to 100:1 and incubation period from 16 to 20 hr were optimal for determination of cytotoxicity. The lymphocyte induced chromium release was not obviously correlated with serum mumps hemagglutination-inhibition titers of the effector cell donors. However, the lymphocyte reaction against virus-infected target cells seems to have an immunologic basis. Thus, the more pronounced susceptibility of mumps-infected target cells as compared to non-infected cells was not due to a cytocidal effect of the virus, since spontaneous isotope release from both target cells was the same. Also, cord blood lymphocytes which had exhibited good cytotoxicity when induced either with phytohemagglutinin or with antiserum against target cell antigens were not cytotoxic for mumps-infected Vero cells. Moreover, the lymphocyte reaction against virus infected target cells could be inhibited by high concentrations of hyperimmune rabbit antimumps sera. On the other hand, lower concentrations of antisera specifically poteniated the lymphoycte-mediated isotope release from mumps-infected target cells.

Animals↗
PubMed1975

Plasma therapy: an alternative to gamma globulin injections in immunodeficiency.

The intravenous infusion of fresh-frozen plasma is an alternative to intramuscular immune serum globulin (ISG) injections. When given in doses of 15 ml/kg at 3-week intervals, the IgG levels achieved are significantly higher than those achieved by 0.7 ml/kg of ISG and they persist longer. In addition, IgM and IgA levels are raised slightly. Other advantages of plasma include the avoidance of intramuscular infections, better patient tolerance, and provision of other serum proteins. The chief disadvantages of plasma are the risk of serum hepatitis (which can be minimized by donor selection) and the inconvenience of procurement and administration. However, it is the treatment of choice for Wiskott-Aldrich syndrome, certain opsonic deficiencies and patients refractory, sensitive or unable to have ISG injections.

Agammaglobulinemia↗
PubMed1976

HLA patterns and disease associations.

The a priori biologic significance of the histocompatibility complex with its excessive polymorphism remains unknown. Teleologically, however, the role of the HLA system may be viewed as vital for survival of the species and the individual by providing the host with a recognition system of and defenses against viruses, microorganisms, parasites, plant antigens, neoplastic cells, and others. HLA testing, in addition to its usefulness in donor selection for transplantation, has been recently applied to the diagnosis and differentiation of specific diseases, the prediction of disease development (risk prediction), and as a basis for prognostic evaluations. An increasing number of diseases is being shown to be linked by specific HLA antigens and certain common denominators, such as arthritides, autoimmune components or infections, suggesting common etiologic or pathogenic mechanisms or both. These diseases with HLA associations can be separated into those that appear certain, probable, or only statistically possible.

Autoimmune Diseases↗
PubMedDate not supplied

Selection of compatible platelet donors: a prospective evaluation of three cross-matching techniques.

A prospective study was undertaken to assess the values of platelet aggregometry, lymphocytotoxicity, and mixed lymphocyte cultures in selecting compatible donors for patients refractory to random platelet transfusions. Donors were selected at random without regard to HLA types. Concurrent with each platelet transfusion, platelet aggregometry and lymphocytotoxicity were performed using patient serum and donor cells. The results were compared with HLA types, MLC, and increments in platelet counts. Forty-one transfusions were given to 21 patients; 27 were from related and 14 from unrelated donors. Platelet aggregometry was used successfully in selecting compatible donors in 37 cases (90%) with three false negative and one false positive results. Lymphocytotoxicity was useful in 73 per cent of cases with eight false negative and three false positive results. The response to platelet transfusions correlated poorly with HLA matches or MLC reactions. These data suggest platelet aggregometry and lymphocytotoxicity are useful cross matching techniques in selection of compatible platelet donors.

Adolescent↗
PubMedDate not supplied

Ocurrence of anti-Wr a in blood donors and in selected patient groups, with a note on the incidence of the Wr a antigen.

The occurrence of the Wr a antigen on the red blood cells of 5,000 primarily Caucasian New York State blood donors was shown to be 1:1,000. Anti-Wr a was detected in sera from random blood donors with a frequency of 1:56 and with progressively increasing frequency in postpartum women, patients undergoing open-heart surgery, hemodialysis subjects, and random persons with other alloantibodies. Anti-Wr a was found in one fourth of sera from patients with positive direct antiglobulin tests, including 12 of 23 in whom the positive test was associated with alphamethyldopa treatment.

Adult↗
PubMed1975

Selective IgA deficiency in blood donors.

The frequency of selective deficiency of serum IgA was determined in a population of 64,588 new Finnish blood donors by Ouchterlony's double diffusion with 10 mug/ml as the limit of detection. The incidence was 1:396. Those found IgA-deficient were retested by hemagglutination inhibition and by radioimmunoassay. The calculated incidences of IgA levels below 0.5 and 0.015 mug/ml were 1:500 and 1:800, respectively. Statistically significant compensatory elevation of serum IgG was observed in the IgA-deficient donors. The IgM levels were not changed. Among 9,920 hospital patients, the incidence of IgA deficiency was 1:660. The age structure of the IgA-deficient patients was similar to that of the IgA-deficient healthy blood donors but lower than that of hospital patients in general. No difference was observed between the clinical history of IgA-deficienct blood donors and of the controls.

Adolescent↗
PubMed1978

Histocompatibility (HLA) antigens and keratoplasty.

In 84 cases of keratoplasty, all patients had densely vascularized corneas and a history of prior exposure to HLA antigens by pregnancy, blood transfusion, or previous transplantation. Donors were selected on the basis of a negative crossmatch to avoid donor antigens to which the recipient was preimmunized. The overall rate of graft failure from rejection was 15%. A retrospective analysis of donor-recipient HLA matching in 103 high-risk cases showed no consistent correlation between the number of antigens shared and graft outcome. These findings indicated negative cross-match to be important in donor selection for keratoplasty in high-risk cases.

Adolescent↗
PubMed1979

[Results of blood transfusion in anemia of dairy cattle with references to serological tolerance].

Therapeutic use of blood transfusion as a life-saving step in cases of dairy cattle anaemia cannot be recommended unless serological tolerance is taken into due consideration. The results obtainable from cross-testing and biological testing are useless in avoiding transfusion problems caused by blood groups in situations of first transfusion. Suitable donors can be identified only by haemolysis and haemolysis inhibition tests. Preliminary selection of donors in advance is permissible for first transfusions. The most important antigens, which may correspond with normal agglutinins, must not be present in the blood patterns of selected donors. Blood transfusion without knowledge of serological tolerance and compatibility between donor and recipient may be justified in emergency situations, yet, together with desensitisation.

Anemia↗