Cellular Characterization of the Gouty Tophus: A Quantitative Analysis

Arthritis Rheum. 2010 May;62(5):1549-56. doi: 10.1002/art.27356.

Abstract

Objective: To characterize the cellular architecture of the tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation.

Methods: Sixteen fixed, paraffin-embedded, uninfected tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the tophus was analyzed by Genmod mixed models analysis.

Results: Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1beta (IL-1beta) were observed in the corona zone. Transforming growth factor beta1 (TGFbeta1)-expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1beta (r = 0.691, P = 0.009) and the number expressing TGFbeta1 (r = 0.518, P = 0.04).

Conclusion: The tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1beta and TGFbeta1 suggests that both proinflammatory and antiinflammatory factors present within the tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, CD20 / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Crystallization
  • Female
  • Gout / immunology*
  • Gout / metabolism
  • Gout / pathology*
  • Humans
  • Immunohistochemistry
  • Interleukin-1beta / metabolism
  • Leukocytes / metabolism*
  • Leukocytes / pathology*
  • Male
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Middle Aged
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Transforming Growth Factor beta1 / metabolism
  • Uric Acid / chemistry
  • Uric Acid / metabolism

Substances

  • Antigens, CD
  • Antigens, CD20
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Interleukin-1beta
  • Transforming Growth Factor beta1
  • Uric Acid