Mast cell responses in rheumatoid synovium. Association of the MCTC subset with matrix turnover and clinical progression

Abstract

Objective. To determine the distribution of mast cell subsets and their density in synovium from normal subjects and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. A sequential double-immunohisto-chemical staining technique was used to distinguish mast cells as positive for tryptase only (MC_T) or for tryptase plus chymase (MC_TC). Synovial tissue was obtained from RA patients (n = 16), OA patients (n = 18), and normal subjects (n = 15). Sections were analyzed to a depth of 1 mm from the synoviocyte lining layer by quantitative histomorphometry. Immunohisto-chemical data were correlated with histologic findings and clinical indices of disease activity. Results. In normal synovium, the majority of mast cells belonged to the MC_TC subset, outnumbering MC_T cells by 5:1. The mean density of mast cells was significantly increased in RA synovia (60.9 cells/mm²) compared with OA (21.7 cells/mm²) and with normal (9.4 cells/mm²) synovia. Selective expansion of the MC_T subset accounted for the increased mast cell density in OA. In RA, both subsets expanded and were associated with infiltrating inflammatory cells or with regions of highly cellular fibrous tissue (mainly MC_TC). An association was noted between clinical parameters of activity or progression of rheumatoid disease and the density of MC_TC cells, especially the density in the superficial layer of synovium. In RA synovia, we found no evidence of the chymase only, or MC_C, immunophenotype. Conclusion. MC_TC mast cells expand in RA but not OA, associate with regions of “active” fibrosis, and correlate with parameters of disease activity or progression of RA. These findings implicate the MC_TC subset of mast cells in the pathologic mechanisms that mediate tissue damage in RA.