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Published on: February 8, 2019
Cellular characterization of the gouty tophus: a quantitative analysis
Nicola Dalbeth1, Bregina Pool, Greg D Gamble
1University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz
Insights
Gout tophi show a complex inflammatory cell structure with both pro-inflammatory (IL-1beta) and anti-inflammatory (TGFbeta1) factors, suggesting a cycle of chronic inflammation and tissue repair.
Area of Science:
- Immunology
- Pathology
- Rheumatology
Background:
- Gouty inflammation involves complex cellular interactions within tophi.
- Understanding tophus cellular architecture is crucial for managing chronic gouty arthritis.
Purpose of the Study:
- To characterize the cellular makeup of gout tophi.
- To identify cytokines involved in gout inflammation and resolution.
Main Methods:
- Quantitative immunohistochemistry on 16 gout tophi samples.
- Analysis of cell populations in tophus corona and fibrovascular zones.
- Statistical analysis using Genmod mixed models.
Main Results:
- Tophi contain abundant CD68+ cells, mast cells, and plasma cells, with few neutrophils.
- B cell aggregates were found in 50% of patients.
- Interleukin-1beta (IL-1beta) and Transforming Growth Factor beta1 (TGFbeta1) expressing cells were prevalent.
- CD68+ cell counts correlated with IL-1beta and TGFbeta1 expression.
Conclusions:
- Tophi represent organized chronic inflammation involving innate and adaptive immunity.
- Coexpression of IL-1beta and TGFbeta1 suggests a balance between inflammation and resolution.
- This cellular interplay may drive chronic inflammation and tissue remodeling in gout.
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.