Neutralizing antibodies in gene-defective hosts.
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.
Opdenakker
Ghislain
G
Rega Institute for Medical Research, Laboratory of Immunobiology, University of Leuven, Minderbroedersstraat 10, Belgium. ghislain.opdenakker@rega.kuleuven.ac.be
Van den Steen
Philippe E
PE
Laureys
Geneviève
G
Hunninck
Kathleen
K
Arnold
Bernd
B
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
D007518:Isoantibodies