Protein-methotrexate-IgG complexes in the serum of patients receiving high-dose antifolate therapy

Three patients who were treated repetitive courses of high-dose methotrexate and leucovorin rescue experienced hypersensitivity symptoms infusion of the drug. Serum from all three patients contained one complex of methotrexate bound to a protein similar in size to albumin and a second complex of the protein-bound methotrexate coupled to IgG. This immune complex was not found in 4 patients similarly treated who did not experience hypersensitivity symptoms.