title: The absence of human beta 2-microglobulin increases the occurrence of ankylosing enthesopathy in HLA-B27 transgenic mice.
abstract: HLA-B27 transgenic mice develop a spontaneous ankylosing enthesopathy (ANKENT). We have investigated the occurrence of ANKENT in transgenic mice carrying transgenes for human beta 2-microglobulin (M TGM), HLA-B27-heavy chain (27 TGM), or both (27M TGM). An unexpected finding was the increase in ANKENT occurrence among the HLA-B27 transgenic mice lacking the human beta 2-microglobulin transgene (27 TGM): 33% of such mice were found to develop ANKENT, whereas 19% of 27M mice were diseased. In addition, the expression of HLA-B27 molecules in individual 27 TGM was highly variable, ranging from no expression to a level similar to that observed in 27M TGM. Our results confirm that in mice the HLA-B27 transgene is a relative risk factor for ANKENT. The increase of ANKENT occurrence is HLA-B27 transgenics in the absence of human beta 2-microglobulin suggests a possible role for impaired cell surface expression of HLA-B27. The absence of human beta 2-microglobulin might entail an accumulation of unassembled HLA-B27 heavy chains. Exposure of these mice to an environmental trigger could then lead to an inappropriate immune response which might result in disease development.
authors.affiliation: Mouse Immunogenetics, U93 INSERM, Saint-Louis Hospital, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Chopin
authors.forename: R
authors.initials: R
authors.lastname: Plichtova
authors.forename: B
authors.initials: B
authors.lastname: Urbero
authors.forename: M
authors.initials: M
authors.lastname: Pla
mesh_terms: D000818:Animals; D000844:Ankylosis / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012216:Rheumatic Diseases / Q000276:immunology / Q000503:physiopathology*; D001613:beta 2-Microglobulin / Q000032:analysis* / Q000276:immunology
chemical_list: D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin