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Cross-reactivity studies of horse, goat and rabbit anti-lymphocyte globulin.

Abstract: In the sera of ten normal humans and twenty-eight candidates for organ transplantation, the passive haemagglutination test detected a 50% incidence of preformed antibodies of low titre directed against horse serum. Such antibodies were also found to cross react with goat or rabbit sera in most instances. Seventeen of the organ recipients were later studied after the institution of treatment with horse antihuman-lymphocyte globulin (ALG). The incidence of anti-horse-serum antibodies rose to 100%. At the same time, an increased activity against goat serum developed; cross-reactions against rabbit serum were also demonstrated but to a less pronounced degree. With immunoelectrophoresis and Ouchterlony diffusion tests, it was shown that the cross-reactivity was to similar although not necessarily identical protein components of the different heterologous sera. These data suggest that there is an inherent risk in switching from one ALG to another, particularly if horse and goat derivatives are used sequentially. Since rabbit ALG does not cross react so extensively with horse or goat serum it would be predicted to be a relatively safer second-line agent. These expectations seemed to have been realized in six patients who were given more than one kind of ALG, always beginning with horse globulin. When goat ALG was administered second, anaphylactic reactions tended to appear early, but when the rabbit product was given second or third, it was relatively well tolerated.
Publication Date: 1970-02-01 PubMed ID: 4985160PubMed Central: PMC1712782
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  • Journal Article

Summary

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The research study investigates the occurrence of preformed antibodies against horse serum in humans, as well as their cross-reactions with goat and rabbit sera. The results suggest a potential risk in switching from one type of anti-lymphocyte globulin (ALG) to another, especially from horse to goat derivatives.

Identification of Antibodies in Human Sera

  • The study first analyzed sera taken from ten healthy individuals and twenty-eight candidates for organ transplantation.
  • Using a passive haemagglutination test, the researchers identified a 50% incidence of preformed antibodies of low titre directed against horse serum. This indicates that half of the participants exhibited an immune response to horse serum.

Cross-reactivity study

  • The researchers also found that there was a cross-reactivity between the identified antibodies and goat or rabbit sera. This means that the identified antibodies not only target horse serum but also react to goat and rabbit serum.
  • This cross-reactivity was identified in most instances, showing a common occurrence of response against these different animal sera.

Observation Post-treatment with ALG

  • The study then followed up with seventeen of the organ recipients who had undergone treatment with horse antihuman-lymphocyte globulin (ALG).
  • Post-treatment, there was a 100% incidence of antibodies against horse serum. This is an increase compared to the pre-treatment incidence.
  • Post-treatment, the activity against goat serum also increased. Cross-reactions against rabbit serum were present, but less pronounced.

Identification of Cross-reacting Protein Components

  • Using immunoelectrophoresis and Ouchterlony diffusion tests, the researchers showed that the cross-reactivity was due to similar, but not necessarily identical, protein components in the different animal sera.
  • This suggests a response based on protein structures present in more than one type of serum.

Inherent Risks in Switching ALGs

  • The results of the study point to a potential risk in switching from one ALG to another, specifically if horse and goat derivatives are used sequentially.
  • Rabbit ALG, which exhibited less extensive cross-reactivity with horse or goat serum, could be a relatively safer second-line agent.
  • These expectations seemed to hold true in six patients who were given more than one type of ALG. They began with horse globulin and when goat ALG was administered second, anaphylactic reactions tended to appear early, but when the rabbit ALG was given second or third, it was generally better tolerated.

Cite This Article

APA
Ameniya H, Kashiwagi N, Putnam CW, Starzl TE. (1970). Cross-reactivity studies of horse, goat and rabbit anti-lymphocyte globulin. Clin Exp Immunol, 6(2), 279-289.

Publication

ISSN: 0009-9104
NlmUniqueID: 0057202
Country: England
Language: English
Volume: 6
Issue: 2
Pages: 279-289

Researcher Affiliations

Ameniya, H
    Kashiwagi, N
      Putnam, C W
        Starzl, T E

          MeSH Terms

          • Animals
          • Antigen-Antibody Reactions
          • Antilymphocyte Serum / therapeutic use
          • Cross Reactions
          • Goats
          • Hemagglutination Tests
          • Horses
          • Humans
          • Immunodiffusion
          • Immunoelectrophoresis
          • Kidney Transplantation
          • Liver Transplantation
          • Rabbits
          • Species Specificity
          • Transplantation, Homologous

          References

          This article includes 10 references
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          Citations

          This article has been cited 5 times.
          1. James K, Pullar DM, Morton JB, Dalton RG, Nolan B, Woodruff MF. The intravenous administration of equine antilymphocytic globulin in renal transplant recipients and the detection of circulating antibodies to equine globulin.. Clin Exp Immunol 1971 Apr;8(4):529-42.
            pubmed: 4995934
          2. Amemiya H, Yokoyama T, Torisu M, Putnam CW, Anderson JT, Starzl TE. The reduction of antigenicity of heterologous antilymphocyte serum with acid Taka-protease.. Clin Exp Immunol 1972 May;11(1):67-81.
            pubmed: 4624986
          3. Amemiya H, Yokoyama T, Putnam CW, Torisu M, Starzl TE. The nature of antiplatelet activity in antilymphoblast ALG--with special reference to cross-reacting antibody, immunochemical characterization, and Coombs' positive thrombocytopenia in ALG-treated renal recipients.. Clin Exp Immunol 1972 Mar;10(3):417-26.
            pubmed: 4556008
          4. Allardyce RA, Anderson NF, Vaerman JP, James K. The antigenic and immunosuppressive properties of normal and antilymphocytic equine IgG subfractions.. Clin Exp Immunol 1973 Feb;13(2):263-78.
            pubmed: 4120853
          5. Henricsson A, Husberg B, Bergentz SE. The mechanism behind the effect of ALG on platelets in vivo.. Clin Exp Immunol 1977 Sep;29(3):515-22.
            pubmed: 589869