title: Neutralizing antibodies in gene-defective hosts.
abstract: In a host with a normal immune system and a complete gene defect, the nondefective gene product will be immunogenic. Consequently, neutralizing antibodies against the respective protein can arise either 'spontaneously' or after immunization, as shown in patients and in animal models, such as knockout mice. Accordingly, patients with X-linked or homozygous autosomal gene defects are at risk of developing neutralizing antibodies, in particular after protein substitution or gene therapy. This Review compares and exemplifies the various genetic and immunological contexts that lead to 'neutralizing and generated by gene defect' or 'nagged' antibodies, and outlines implications and solutions for therapeutic strategies.
authors.affiliation: Rega Institute for Medical Research, Laboratory of Immunobiology, University of Leuven, Minderbroedersstraat 10, Belgium. ghislain.opdenakker@rega.kuleuven.ac.be
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Van den Steen
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hunninck
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000276:immunology*; D008040:Genetic Linkage; D006467:Hemophilia A / Q000235:genetics / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009500:Neutralization Tests; D014960:X Chromosome
chemical_list: D007518:Isoantibodies