In vitro demonstration of IgE antibody to folate-albumin in anaphylaxis from folic acid

Background: Folic acid (the synthetic form of folate B vitamins in foods) i s widely used in vitamin supplements, Anaphylaxis from ingestion or injecti on of folic acid suggests IgE antibody-mediated mechanisms, but this has no t been demonstrated previously in vitro. Objective: This study was conducted to better define the mechanism of folic acid hypersensitivity and cross-reactivity among folic acid congeners, Methods: Skin testing was performed with folic acid congeners in a woman wh o developed anaphylaxis after ingestion of 2 different multivitamin prepara tions containing folic acid. In vitro immunologic serum studies were conduc ted using a Folate-human serum albumin (HSA) conjugate prepared by a novel application of carbodiimide condensation. Results: The patient had positive immediate-type skin test reactions to fol ic acid and several folate analogues including leucovorin (folinic acid). U rticaria developed during graded oral test dosing with leucovorin, Using a dot immunoblot assay or an ELISA for IgE antibody to folate-HSA, results of the patient's serum testing were positive, whereas results of sera From no rmal control subjects were negative, the first in vitro demonstration of Ig E to a folic acid-protein conjugate, By ELISA, the positive result of the p atient's serum was inhibited significantly by serum coincubation with folat e-HSA, but not HSA or folic acid. Conclusions: Immediate hypersensitivity to folic acid and possibly other vi tamins can be mediated by IgE antibody to conjugates formed between vitamin s and self-proteins or polypeptides. Leucovorin can have clinically importa nt immunologic cross-reactivity with folic acid. A diet rich in natural fol ates (pteroylpolyglutamates) appears useful as a management strategy for pr oviding adequate nutrition to patients with folic acid hypersensitivity.