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

Abstract

Folic acid (the synthetic form of folate B vitamins in foods) is widely used in vitamin supplements. Anaphylaxis from ingestion or injection of folic acid suggests IgE antibody-mediated mechanisms, but this has not been demonstrated previously in vitro. This study was conducted to better define the mechanism of folic acid hypersensitivity and cross-reactivity among folic acid congeners. Skin testing was performed with folic acid congeners in a woman who developed anaphylaxis after ingestion of 2 different multivitamin preparations containing folic acid. In vitro immunologic serum studies were conducted using a folate-human serum albumin (HSA) conjugate prepared by a novel application of carbodiimide condensation. The patient had positive immediate-type skin test reactions to folic acid and several folate analogues including leucovorin (folinic acid). Urticaria 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 normal control subjects were negative, the first in vitro demonstration of IgE to a folic acid-protein conjugate. By ELISA, the positive result of the patient's serum was inhibited significantly by serum coincubation with folate-HSA, but not HSA or folic acid. Immediate hypersensitivity to folic acid and possibly other vitamins can be mediated by IgE antibody to conjugates formed between vitamins and self-proteins or polypeptides. Leucovorin can have clinically important immunologic cross-reactivity with folic acid. A diet rich in natural folates (pteroylpolyglutamates) appears useful as a management strategy for providing adequate nutrition to patients with folic acid hypersensitivity.