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. 1998 Nov;57(11):664–671. doi: 10.1136/ard.57.11.664

Synovial mast cell responses during clinical improvement in early rheumatoid arthritis

I Gotis-Graham 1, M Smith 1, A Parker 1, H McNeil 1
PMCID: PMC1752502  PMID: 9924208

Abstract

OBJECTIVES—To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity.
METHODS—Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MCT and MCTC mast cells and correlations were sought between clinical and histological data.
RESULTS—The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MCT subset predominated, outnumbering MCTC by 3:1. There was a significant correlation between the histological inflammation index and the MCT density, (r = 0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement.
CONCLUSIONS—The mast cell response in early RA is characterised by substantial expansion of predominantly MCT mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MCTC cells in synovial damage and disease progression, these results suggest that MCT and MCTC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.



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Figure 1  .

Figure 1  

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Two µm serial sections of skin (a) (b), tonsil (c) (d), and 4 µm sections of RA synovium (e) (f) (g) (h) were stained for tryptase (a) (c) (e) (g) and with avidin (b) (d) (f) (h). The arrows indicate the synoviocyte lining layer. In skin where > 99% of mast cells are MCTC, all avidin positive cells (b) (cells 1-6) stained for tryptase (a), confirming that avidin detects MCTC mast cells. In tonsil, no avidin positive cells (d) were found beneath the capsule (cap) or around lymphoid follicles where MCT are known to be present (c), indicating that avidin does not bind to MCT mast cells. These staining results are consistent with the known distribution of MCTC within skin and tonsil and validate avidin as a marker of MCTC. Adjacent sections from a patient with RA (e) (f) show MCTC around subsynovial venules in an area with relatively few lymphocytes and a thin synovial lining layer. The tryptase positive mast cells in (e) also stain with avidin (f). Adjacent sections from another RA patient (g) (h) show MCT around a collection of lymphocytes, underneath a hyperplastic synovial lining layer. Tryptase positive mast cells (g) are not detected with avidin (h), indicating these cells are MCT. Magnification: all at × 500, except (g) (h) at × 312. 

Figure 2  .

Figure 2  

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Relation of mast cells to inflammation index. There was a significant correlation between (a) total mast cell density and the inflammation index (r = 0.39, p < 0.05). When mast cell subsets were examined, this relation was because of the MCT subset, with (b) a significant correlation between MCT density and the inflammation index (r = 0.4, p < 0.05). (c) No correlation was observed between the inflammation index and the MCTC density.

Figure 3  .

Figure 3  

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The changes in synovial mast cell density between final and baseline biopsies. Each point represents the changes seen in the superficial or deeper layers of synovia from patients 1 to 6. 

Figure 4  .

Figure 4  

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Individual patient mast cell responses at different time points. In patient (a), the total mast cell density remained stable over the study period. However, the MCT density decreased while there was a reciprocal increase in MCTC density. In patient (b), there was a dramatic reduction in total mast cell density after intravenous methylprednisolone, and over subsequent biopsies there was a progressive increase in the MCT density.

Selected References

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