HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human β2-microglobulin (β2m) double transgenic mice with disrupted mouse β2m

Sanjay D. Khare, Julie Hansen, Harvinder S. Luthra, Chella S. David

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

MHC class 1 allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous β2-microglobulin (β2m) gene was replaced with transgenic human β2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs. These mice developed spontaneous arthritis and nail changes in the rear paws. Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area. Transgenic mice expressing HLA- B27 with mouse β2m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease. Our data demonstrate specific involvement of HLA-B27 'free' HCs in the disease process.

Original languageEnglish (US)
Pages (from-to)2746-2755
Number of pages10
JournalJournal of Clinical Investigation
Volume98
Issue number12
DOIs
StatePublished - Dec 15 1996

Keywords

  • HLA-B27
  • Reiter's disease
  • animal model
  • heavy chain
  • spondyloarthropathy

ASJC Scopus subject areas

  • Medicine(all)

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