Downregulation of RCAS1 and Upregulation of Cytotoxic T Cells Affects Synovial Proliferation and Apoptosis in Rheumatoid Arthritis

SHIRO YOSHIDA, FUJIO HIGUCHI, YUMIKO ISHIBASHI, MASAFUMI GOTO, YASUO SUGITA, YUKO NOMURA, KENNOSUKE KARUBE, KEI SHIMIZU, RYOSUKE AOKI, HIDEKI KOMATANI, KEIKO HASHIKAWA, YOSHIZO KIMURA, MANABU NAKASHIMA, KENSEI NAGATA, and KOICHI OHSHIMA

ABSTRACT.

Objective. The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells. This seems to be the result of the proliferation and apoptosis induced by immune balance. We studied the involvement of RCAS1 and the infiltration of cytotoxic T lymphocytes (CTL), and examined the synovium immunohistochemically to determine the involvement of proliferation and apoptosis in synovial lining cells, and their relationship with the activity of RA Treg cells in the germinal center.

Methods. We used double-immunological staining of Ki-67 and caspase-3 to investigate proliferation and apoptosis. We analyzed CTL, regulatory T cells (Treg), and receptor-binding cancer antigen expressed on SiSo cells (RCAS1), recently recognized to play a role in immune evasion. Proliferation and apoptosis were more frequently encountered in synovial lining cells in RA than in those in osteoarthritis (OA) that were used as a control.

Results. High expression of RCAS1 was detected more frequently in the synovial lining cells of OA, but CTL infiltration into the synovium was rarely found. In RA, on the other hand, CTL were observed, while RCAS1 expression was lacking. We compared the presence of Foxp3-positive cells with the level of C-reactive protein (CRP) that served as an active inflammatory marker. Foxp3-positive cells in the germinal center and in CRP showed possible correlation in terms of the range of inflammatory states.

Conclusion. In RA, the lack of RCAS1 is thought to induce CTL infiltration through loss of the ability to evade immune attack, thus leading to apoptosis of the synovial lining cells. In addition, Treg cells may play a role in the downregulation of activated T cells. (First Release Aug 1 2008; J Rheumatol 2008;35:1716-22)

Key Indexing Terms:

RCAS1
APOPTOSIS
PROLIFERATION
RHEUMATOID ARTHRITIS
CASPASE-3
Ki-67
Foxp3
SYNOVIUM

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From the Department of Pathology and Department of Orthopaedic Surgery, School of Medicine, Kurume University, Kurume; and the Department of Pharmaceutical Sciences, Clinical Pharmacology, Fukuoka University, Fukuoka, Japan.

S. Yoshida, MD, Department of Pathology and Department of Orthopaedic Surgery, School of Medicine, Kurume University; F. Higuchi, MD; Y. Ishibashi, MD; M. Goto, MD, Department of Orthopaedic Surgery, School of Medicine, Kurume University, Medical Center; Y. Sugita, MD; Y. Nomura, MD; K. Karube, MD; K. Shimizu, MD; R. Aoki, MD; H. Komatani, MD; K. Hashikawa, MD; Y. Kimura, MD, Department of Pathology, School of Medicine, Kurume University; M. Nakashima, MD, Department of Pharmaceutical Sciences, Clinical Pharmacology, Fukuoka University; K. Nagata, MD, Department of Orthopaedic Surgery, School of Medicine, Kurume University; K. Ohshima, MD, Department of Pathology, School of Medicine, Kurume University.

Address reprint requests to Dr. S. Yoshida, Department of Pathology, School of Medicine, Kurume University, Asahi-machi 67, Kurume-city, Fukuoka 830-0011, Japan. E-mail: marine7blue@hotmail.com

Accepted for publication April 10, 2008.

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