Antibody Formation to Equine Anti-Lymphocytic Globulin (ALG) in Man: Effect on Absorption, Distribution and Effectiveness of the ALG

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Abstract
Increased rates of plasma clearance of 125I-labeled horse IgG were observed in 16 of 17 patients treated with a prolonged course of anti-lymphocytic globulin (ALG) and in 3 of 5 volunteers who received a single small dose of ALG. Rapid immune elimination of ALG developed within 2 weeks of starting ALG treatment, and was accompanied by (1) the development of circulating anti-horse IgG antibodies which could be measured by passive hemagglutination or immunoadsorbent assays and by (2) the return of established delayed hypersensitivity which initially had been suppressed by the ALG treatment. Radioactively labeled horse IgG was found in the 7S region of sera of four patients tested before development of rapid immune elimination. In three patients studied after onset of rapid immune elimination of horse IgG, the serum proteinbound radioactivity sedimented more rapidly than 7S in the ultracentrifuge. In one case, the labeled protein was completely removed from the circulation within minutes of injection and broken down into small molecular weight fragments. Absorption of ALG after intramuscular injection was impaired in the presence of anti-horse IgG antibodies. These results suggest (1) that antibodies form in allograft recipients against ALG despite simultaneous treatment with large doses of azathioprine and corticosteroids, and (2) that these antibodies interfere with the absorption, distribution and the immunosuppressive effectiveness of ALG.

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