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Proc Assoc Am Physicians. 1997 Sep;109(5):462-9.

Autoantibodies in pernicious anemia type I patients recognize sequence 251-256 in human intrinsic factor.

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1
Department of Gastroenterology, Faculty of Medicine, Henri Poincaré University, Vandoeuvre-lès-Nancy, France.

Abstract

Pernicious anemia is an organ-specific autoimmune disease characterized by cobalamin deficiency, megaloblastic anemia, neuropathy, and autoimmune gastritis with anti-intrinsic factor autoantibodies. Type 1 anti-intrinsic factor autoantibodies block the cobalamin binding site of the intrinsic factor, a gastric protein required for the assimilation of cobalamin. The aim of our study was to identify the epitope domain of type 1 antibodies. Different series of peptides derived from the intrinsic factor sequence were synthesized and tested for antibody binding in enzyme-linked immunosorbent assay, radioisotope assay, gel filtration, and SDS-PAGE autoradiography. One of these peptides, named IF-R7 (the intrinsic factor aminoacid sequence 251-265), showed a type 1 antibody binding activity and inhibited, in vitro, their blocking activity with Ki at 2.3 microM. The cross-linking of IF-R7 to beta-lactoglobulin produced type 1 anti-intrinsic factor antibodies in immunized sheep. In vivo Schilling tests performed on guinea pigs also revealed IF-R7 peptide inhibition of type 1 antibody blocking activity. 256Ser, 258Lys, 262Tyr and 265Val of the IF-R7 were essential for the epitope recognition. Reactivity with type 1 antibodies was found in IF-R7 homologous peptides from herpesvirus Saimiri and from pathogenic Escherichia coli. In conclusion, the epitope of type 1 anti-intrinsic factor autoantibodies is located in the 251-265 amino acid sequence of the protein. The identification of this epitope will enable the definition of an experimental animal model of anti-IF autoimmunity in order to study the pathogenesis of pernicious anemia.

PMID:
9285945
[Indexed for MEDLINE]
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