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

98 Citations (Scopus)

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
StatePublished - Dec 15 1996

Fingerprint

HLA-B27 Antigen
Transgenic Mice
Arthritis
Heavy Chain Disease
Spondylarthropathies
Nails
Genes
Blood Cells
Epithelium
Alleles
Antibodies
Infection

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human β2-microglobulin (β2m) double transgenic mice with disrupted mouse β2m. / Khare, Sanjay D.; Hansen, Julie; Luthra, Harvinder S.; David, Chella S.

In: Journal of Clinical Investigation, Vol. 98, No. 12, 15.12.1996, p. 2746-2755.

Research output: Contribution to journalArticle

@article{9b76802796654104ba18c63d45526869,
title = "HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human β2-microglobulin (β2m) double transgenic mice with disrupted mouse β2m",
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.",
keywords = "animal model, heavy chain, HLA-B27, Reiter's disease, spondyloarthropathy",
author = "Khare, {Sanjay D.} and Julie Hansen and Luthra, {Harvinder S.} and David, {Chella S.}",
year = "1996",
month = "12",
day = "15",
language = "English (US)",
volume = "98",
pages = "2746--2755",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

TY - JOUR

T1 - HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human β2-microglobulin (β2m) double transgenic mice with disrupted mouse β2m

AU - Khare, Sanjay D.

AU - Hansen, Julie

AU - Luthra, Harvinder S.

AU - David, Chella S.

PY - 1996/12/15

Y1 - 1996/12/15

N2 - 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.

AB - 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.

KW - animal model

KW - heavy chain

KW - HLA-B27

KW - Reiter's disease

KW - spondyloarthropathy

UR - http://www.scopus.com/inward/record.url?scp=0030482194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030482194&partnerID=8YFLogxK

M3 - Article

VL - 98

SP - 2746

EP - 2755

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 12

ER -