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) 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.


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 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.


RESULTS
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.


CONCLUSIONS
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.
Dykewicz
M S
MS
Division of Allergy and Immunology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Orfan
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NA
Sun
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D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D002352:Carrier Proteins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007073:Immunoglobulin E; D011956:Receptors, Cell Surface; D012709:Serum Albumin / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D012709:Serum Albumin; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D005492:Folic Acid