MAST-CELL RESPONSES IN RHEUMATOID SYNOVIUM - ASSOCIATION OF THE MC(TC) SUBSET WITH MATRIX TURNOVER AND CLINICAL PROGRESSION

Objective. To determine the distribution of mast cell subsets and thei r density in synovium from normal subjects and from patients with oste oarthritis (OA) and rheumatoid arthritis (RA). Methods. A sequential d ouble-immunohistochemical staining technique was used to distinguish m ast cells as positive for tryptase only (MC(T)) or for tryptase plus c hymase (MC(TC)), Synovial tissue was obtained from RA patients (n = 16 ), OA patients (n = 18), and normal subjects (n = 15), Sections were a nalyzed to a depth of 1 mm from the synoviocyte lining layer by quanti tative histomorphometry, Immunohistochemical 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 ce lls was significantly increased in RA synovia (60.9 cells/mm(2)) compa red with OA (21.7 cells/mm(2)) and with normal (9.4 cells/mm(2)) synov ia, Selective expansion of the MC(T) subset accounted for the increase d mast cell density in OA, In RA, both subsets expanded and were assoc iated with infiltrating inflammatory cells or with regions of highly c ellular fibrous tissue (mainly MC(TC)), An association was noted betwe en clinical parameters of activity or progression of rheumatoid diseas e and the density of MC(TC) cells, especially the density in the super ficial layer of synovium, In RA synovia, we found no evidence of the c hymase 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 pa thologic mechanisms that mediate tissue damage in RA.