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Expression of Melanoma Antigen Gene by Cells from Inflamed Joints in Juvenile Rheumatoid Arthritis

DEBORAH K. McCURDY, LEI-QIAN TAI, KAREN L. IMFELD, MICHAEL SCHWARTZ, FRANK ZALDIVAR, and MONIQUE A. BERMAN

ABSTRACT.

Objective.
To determine if synovial fluid (SF) cells from inflamed joints of patients with juvenile rheumatoid arthritis (JRA) express melanoma antigen gene (MAGE) RNA and protein.

Methods. The pattern of MAGE-A1 expression was analyzed in inflammatory synovial tissue and peripheral blood mononuclear cells (PBMC) from patients with JRA by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry.

Results. MAGE-A1, previously detected only in tumor cells, is strongly expressed in SF cells from patients with JRA. Immunocytochemistry revealed strong staining of SF cells in all of 22 specimens tested. PBMC from patients (7 of 7) also expressed MAGE-A1, but not as strongly as SF cells. Two-color immunofluorescence showed colocalization with CD4 and CD14. Flow cytometry on 3 samples of SF cells confirmed the presence of MAGE-A1 on the cell surface and intracellularly. Five of 5 SF cell samples were positive for MAGE-A1 by RT-PCR.

Conclusion. Mononuclear cells from inflamed joints and blood from patients with JRA express MAGE-A1. MAGE family proteins were previously thought to be expressed only by certain tumors and presented by HLA Class I, resulting in tumor cell lysis by cytotoxic T cells. The observation of MAGE-A1 expression in JRA suggests an association with autoimmune disease and a possible causal role for MAGE antigen in the chronic inflammation of JRA. (J Rheumatol 2002;29:2219-24)

Key Indexing Terms:

AUTOIMMUNITY
RHEUMATOID ARTHRITIS
CHRONIC INFLAMMATION
ANTIGEN
MAGE
ANTIGEN PRESENTATION


From the Division of Rheumatology and CHOC Research Institute, Children's Hospital of Orange County, Orange, California, USA.

Supported by grants from the Arthritis Foundation, So. California Chapter, Children's Hospital of Orange County Padrinos Foundation, and Pediatric & Adolescent Diabetes Research and Education (PADRE) Foundation.

D.K. McCurdy, MD; L-Q. Tai, Pharm D; K.L. Imfeld, BS; M. Schwartz, BS; F. Zaldivar, PhD; M.A. Berman, PhD.

Address reprint requests to Dr. D. McCurdy, Division of Rheumatology, Children's Hospital of Orange County, 455 South Main Street, PO Box 5700, Orange, CA 92613-5700. E-mail: dmccurdy@choc.org

Submitted November 21, 2001; revision accepted April 1, 2002.




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