Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


A New Humanized Mouse Model for Experimental Erosive Arthritis: A Possible Role of Epstein-Barr Virus (EBV) for Experimental Erosive Arthritis That Resembles Rheumatoid Arthritis (RA).

Kuwana5,  Yoshikazu, Takei5,  Masami, Yajima3,  Misako, Inomata6,  Hirotake, Shiozaki7,  Masaaki, Ikumi7,  Natsumi, Nozaki7,  Takamasa

Central Institute for Experimental Animals, Kawasaki, Japan
Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Department of Virology, Division of Medical Science, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Itabashi Tokyo, Japan
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Itabashi Tokyo, Japan
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

Purpose:

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by destructive synovitis and systemic immunologic abnormalities. In this study, whether Epstein-Barr virus (EBV) infection could result in erosive arthritis that resembles RA in NOD/Shi-scid/IL-2Rnull (NOG) mice was examined.

Methods:

NOG mice, a highly immunodeficient mouse strain, in which the functional human immune system is reconstituted when they receive hematopoietic stem cell (HSC) transplants, were used. Human CD34+ HSCs were obtained from cord blood using a magnetic-activated cell sorting (MACS) direct CD34 Progenitor Cell Isolation Kit. These CD34+ cells (1×104 to 1.2×105 cells/mouse) were injected intravenously into 6–10-week-old, female, NOG mice. The NOG mice were inoculated intravenously through the tail vein with EBV (100-103 TD50) on days 106 to 180 after stem cell transplantation. EBV DNA in peripheral blood was quantified by a real-time quantitative polymerase chain reaction (PCR) assay based on the TaqMan system (Applied Biosystems) 1 to 4 months after inoculation. One, two, six, and twelve months after being inoculated with EBV, the humanized NOG mice were sacrificed, and their joints were examined pathologically. The joint tissues were stained with hematoxylin-eosin (H-E) stain, and immunostaining and EBV in situ hybridization were performed.

Results:

The joint tissues of the mice revealed pannus invading bone tissue, synovial membrane proliferation, and inflammatory tissues infiltrating the bone marrow (BM) space. Human CD4+ T cells were seen proliferating to the synovium and the BM near joints. Migration of large multinuclear giant cells, thought to be osteoclasts, was also evident in the pannus site. EBV-infected cells were mainly conformed within the BM of the EBV-inoculated NOG mice, but there were few EBV-infected cells in the synovium.

Conclusions:

In this study, bone erosion accompanied by pannus and synovial membrane proliferation was confirmed at the joints of EBV-inoculated NOG mice. Further, some EBV-inoculated NOG mice revealed BM erosion as a result of the inflammatory cell infiltration. The results of this study suggest that EBV-inoculated NOG mice develop erosive arthritis that resembles RA.

To cite this abstract, please use the following information:
Kuwana, Yoshikazu, Takei, Masami, Yajima, Misako, Inomata, Hirotake, Shiozaki, Masaaki, Ikumi, Natsumi, et al; A New Humanized Mouse Model for Experimental Erosive Arthritis: A Possible Role of Epstein-Barr Virus (EBV) for Experimental Erosive Arthritis That Resembles Rheumatoid Arthritis (RA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1708
DOI: 10.1002/art.29473

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