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MIROSLAV HARJACEK, SALVADOR DIAZ-CANO, MANUEL DE MIGUEL, HUBERT WOLFE, CRISTINA A. MALDONADO, and GABRIEL A. RABINOVICH

ABSTRACT.

Objective. Juvenile idiopathic arthritis (JIA) is characterized by hyperplasia of synovial cells and accumulation of mononuclear inflammatory infiltrates, which are locally maintained through a balance between cell proliferation and apoptosis. Although defective clearance of activated T cells in RA joints has been explained by alterations of the Fas-Fas ligand system, this has not been confirmed in synovial tissue of patients with JIA. We evaluated the relation between expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) (ß-galactoside-binding proteins with pro- and anti-apoptotic properties, respectively) and the apoptosis and proliferation rates of infiltrative lymphocytes in synovial tissue of patients with JIA.

Methods. Using slide cytometry and in situ end labeling we observed dysregulated apoptosis of infiltrating mononuclear cells within the synovial tissue of patients with JIA.

Results. Patients with pauciarticular JIA showed minimal apoptosis, high Bcl-2 expression, and high or normal proliferation rates, while patients with polyarticular disease showed the lowest apoptotic indexes, accompanied by low Bcl-2 expression and low proliferation rates. We found that Gal-1 expression is downregulated and Gal-3 expression is upregulated in synovial tissue from patients with JIA.

Conclusion. In patients with polyarticular JIA, accumulation of inflammatory cells is mainly due to downregulated apoptosis, whereas in patients with pauciarticular disease the process results from increased proliferation. Defective mononuclear apoptosis in synovial inflammatory infiltrates from patients with JIA could be explained in part by decreased Gal-1 and increased Gal-3 expression. (J Rheumatol 2001;28:1914-22)

Key Indexing Terms:

APOPTOSIS
Bcl-2
GALECTIN-1
GALECTIN-3
JUVENILE IDIOPATHIC ARTHRITIS
SYNOVIAL PROLIFERATION