Cellular characterization of the gouty tophus: a quantitative analysis.
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).


CONCLUSIONS
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.
Dalbeth
Nicola
N
University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz
Pool
Bregina
B
Gamble
Greg D
GD
Smith
Timothy
T
Callon
Karen E
KE
McQueen
Fiona M
FM
Cornish
Jillian
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D003460:Crystallization; D005260:Female; D006073:Gout / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D014527:Uric Acid; C067980:CD68 antigen, human; D000097382:CD68 Molecule