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Annals of surgery1976; 184(3); 352-368; doi: 10.1097/00000658-197609000-00013

Seven years’ experience with antilymphoblast globulin for renal transplantation from cadaver donors.

Abstract: Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.
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Publication Date: 1976-09-01 PubMed ID: 786192PubMed Central: PMC1344397DOI: 10.1097/00000658-197609000-00013Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper presents an analysis of seven years of experience using anti-human lymphoblast globulin (ALG), a type of antibody, in renal transplantation from cadaver donors. The study found improved patient survival and transplant function rates, with a significant reduction in the rejection of grafts and a delayed onset of rejection episodes. However, high doses of ALG were found to be potentially dangerous for older patients with poorly matched donors.

Methodology of ALG Production

  • The study explains that the antibody used, called antilymphoblast globulin (ALG), is derived from horses immunized with human lymphoblasts and Freund’s adjuvant. This substance assists in stimulating the immune system and increasing the response to vaccination.
  • Safety measures for producing this globulin include using early bleedings after immunization (reducing other antibodies), absorbing it with human red blood cell stroma and platelets, stabilizing it with silica dioxide, and completing chromatography to remove unwanted substances.
  • The prepared ALG is tested for toxicity and pyrogenicity in animals and for sterility in vitro.

Benefits and Risks of ALG in Transplants

  • Once properly prepared and safety-tested, ALG can contribute to a standard immunosuppressive regimen for patients, alongside azathioprine and prednisone, reducing the risk of the patient rejecting the transplant.
  • The study demonstrates that allergic reactions to horse IgG are quite rare and that the immune elimination of circulating horse IgG cannot typically be detected in the human circulation.
  • However, treatment with high doses of ALG can be harmful, particularly for older patients or those with poorly matched donors, as they may suffer from an increased incidence of septic loss of kidney and/or life.

ALG’s Impact on Transplant Success

  • The study, based on the results of 184 first cadaver transplants, displays that the use of ALG along with standardized doses of azathioprine and prednisone notably improves patient survival and transplant function.
  • ALG also resulted in a substantial reduction in the number of graft rejects and rejection episodes and a delay in the onset of rejection
  • These results remained consistent, even when controlling for variables like patient age and tissue typing.
  • The paper concludes by suggesting that the dose of ALG should probably be reduced in older patients or those receiving kidneys from poorly matched donors.

Limitations of the Study

  • The paper ends with a caveat that the results of the study are specific to the ALG produced in their center, and might not be replicable with ALG produced elsewhere or by other methods, due to the various factors that affect transplant success or failure.

Cite This Article

APA
Najarian JS, Simmons RL, Condie RM, Thompson EJ, Fryd DS, Howard RJ, Matas AJ, Sutherland DE, Ferguson RM, Schmidtke JR. (1976). Seven years’ experience with antilymphoblast globulin for renal transplantation from cadaver donors. Ann Surg, 184(3), 352-368. https://doi.org/10.1097/00000658-197609000-00013

Publication

Annals of surgery
ISSN: 0003-4932
NlmUniqueID: 0372354
Country: United States
Language: English
Volume: 184
Issue: 3
Pages: 352-368

Researcher Affiliations

Najarian, J S
    Simmons, R L
      Condie, R M
        Thompson, E J
          Fryd, D S
            Howard, R J
              Matas, A J
                Sutherland, D E
                  Ferguson, R M
                    Schmidtke, J R

                      MeSH Terms

                      • Age Factors
                      • Antilymphocyte Serum / adverse effects
                      • Antilymphocyte Serum / isolation & purification
                      • Cadaver
                      • HLA Antigens
                      • Histocompatibility Testing
                      • Humans
                      • Hypersensitivity
                      • Kidney Transplantation
                      • Lymphocytes / analysis
                      • Transplantation, Homologous

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                      Citations

                      This article has been cited 18 times.
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