The Gouty Tophus: a Review

Chhana, Ashika; Dalbeth, Nicola

doi:10.1007/s11926-014-0492-x

Cited by 114 publications

(112 citation statements)

References 74 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Typically, tophi present as subcutaneous nodules many years after initial presentation with acute inflammatory flares [6]. Although advanced age, kidney disease and diuretic use have been reported to be risk factors for development of tophi (reviewed in [7]), few studies have systematically examined the features associated with tophaceous disease.…”

Section: Introductionmentioning

confidence: 99%

Population-specific association between ABCG2 variants and tophaceous disease in people with gout

Phipps‐Green

Stamp

et al. 2017

Arthritis Res Ther

Self Cite

View full text Add to dashboard Cite

BackgroundTophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout. The aim of this study was to examine the role of SLC2A9 and ABCG2 variants in tophaceous disease in people with gout.MethodsParticipants (n = 1778) with gout fulfilling the 1977 American Rheumatism Association (ARA) classification criteria, who were recruited from primary and secondary care, attended a detailed study visit. The presence of palpable tophi was recorded. SLC2A9 rs11942223, ABCG2 rs2231142 and ABCG2 rs10011796 were genotyped. Data were analysed according to tophus status.ResultsCompared to participants without tophi, those with tophi were older, had longer disease duration and higher serum creatinine, and were more likely to be of Māori or Pacific (Polynesian) ancestry. SLC2A9 rs11942223 was not associated with tophi. However, the risk alleles for both ABCG2 single nucleotide polymorphisms (SNPs) were present more frequently in those with tophi (OR (95% CI) 1.24 (1.02–1.51) for rs2231142 and 1.33 (1.01–1.74) for rs10011796, p < 0.05 for both). The effect of rs2231142 was limited to participants of Māori or Pacific ancestry (OR 1.50 (1.14–1.99), p = 0.004), with a significant effect observed in those of Western Polynesian ancestry only (OR 1.71 (1.07–2.72), p = 0.017). The rs10011796 risk allele was strongly associated with tophi in the Western Polynesian group (OR 3.76 (1.61–8.77), p = 0.002), but not in the Eastern Polynesian group (OR 0.87 (0.52–1.46), p = 0.60) nor in the non-Polynesian group (OR 1.16 (0.81–1.66), p = 0.32). The ABCG2 associations persisted in the Western Polynesian group after adjusting for serum urate, creatinine, and disease duration, and when including both ABCG2 variants in the regression models.ConclusionsVariation in ABCG2 function may play a role in the development of tophaceous disease in some populations with high prevalence of severe gout.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1254-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Population-specific association between ABCG2 variants and tophaceous disease in people with gout

Phipps‐Green

Stamp

et al. 2017

Arthritis Res Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…A recent study shed new light on a potential anti-inflammatory role of NETs in gout [5]. At high PMN densities, NETosed PMNs and MSU crystals form ‘aggregated NETs’ (aggNETs), the proposed basis of gouty tophi, a characteristic white material that appears at the beginning of the resolution phase of acute gout flares [5, 24]. Although our view on the role of NETs in gout pathogenesis is improving, less is known how the two most important cell types initiating and mediating inflammation in gout, macrophages and PMNs, interact.…”

Section: Introductionmentioning

confidence: 99%

Macrophage-derived IL-1β enhances monosodium urate crystal-triggered NET formation

et al. 2016

View full text Add to dashboard Cite

Objective and design Arthritic gout is caused by joint inflammation triggered by the damaging effects of monosodium uric acid (MSU) crystal accumulation in the synovial space. Neutrophils play a major role in mediating joint inflammation in gout. Along with neutrophils, other immune cells such as macrophages are present in inflamed joints and contribute to gout pathogenesis. Neutrophils form neutrophil extracellular traps (NETs) in response to MSU crystals. In presence of MSU crystals, macrophages release IL-1β, a cytokine crucial to initiate gout pathogenesis and neutrophil recruitment. Our research investigated interactions between human macrophages and neutrophils in an in vitro model system and asked how macrophages affect NET formation stimulated by MSU crystals. Materials or subjects Human neutrophils and PBMCs were isolated from peripheral blood of healthy volunteers. PBMCs were differentiated into macrophages in vitro using human M-CSF. Treatment Human neutrophils were pretreated with macrophage-conditioned media, neutrophil-conditioned media or recombinant human IL-1β prior to stimulation by MSU crystals. Method Interaction of neutrophils with MSU crystals was evaluated by live imaging using confocal microscopy. The presence of myeloperoxidase (MPO) and neutrophil elastase (NE) was measured by ELISA. NET formation was quantitated by Sytox Orange-based extracellular DNA release assay and NE-DNA ELISA. AggNET formation was assessed by macroscopic evaluation. Results We found that crystal- and cell-free supernatants of macrophages stimulated with MSU crystals promote MSU crystal-stimulated NET formation in human neutrophils. This observation was confirmed by additional assays measuring the release of MPO, NE and the enzymatic activity of NE. MSU crystal-induced NET formation remained unchanged when neutrophil supernatants were tested. IL-1β is a crucial cytokine orchestrating the onset of inflammation in gout and is known to be released in large amounts from macrophages following MSU crystal stimulation. We found that recombinant IL-1β strongly promoted MSU crystal-induced NET formation in human neutrophils. Interestingly, IL-1β alone did not induce any NET release. We also found that clinical grade anakinra, an IL-1 receptor blocker, strongly reduced the NETosis-enhancing effect of macrophage supernatants indicating that IL-1β is mainly responsible for this effect. Conclusions Macrophage-derived IL-1β enhances MSU crystal-induced NET release in neutrophils. We identified a new mechanism by which macrophages and IL-1β affect neutrophil functions and could contribute to the inflammatory conditions present in gout. Our results also revealed a new anti-inflammatory mechanism of anakinra.

show abstract

“…In the present case, the elevation of the patient's bone resorption marker levels might imply that enhanced osteoclastogenesis was involved in the development of bone erosions and destruction. In addition, it is reported that increased levels of pro-inflammatory cytokines such as interleukin (IL)-1β are also associated with the development of bone erosion and destruction (25-27). The levels of these cytokines are elevated in obese subjects.…”

Section: Discussionmentioning

confidence: 99%

Multiple Gouty Tophi with Bone Erosion and Destruction: A Report of an Early-onset Case in an Obese Patient

et al. 2017

View full text Add to dashboard Cite

A 27 year-old severely obese man (BMI, 35.1) had hyperuricemia and multiple gouty tophi with bone erosion and destruction, resulting in gait disturbance for 6 years after the early onset of gout at 21 years of age. His hyperuricemia was associated with hyperinsulinemia in obesity and a genetic variant of the ABCG2 gene. In addition, multiple gouty tophi with bone erosion and destruction might have been caused by hypoadiponectinemia and the elevation of the patient’s pro-inflammatory cytokine (IL-1β) level with the accumulation of visceral fat. In this case, bone and Ga-67 scintigraphy were useful for detecting the location and magnitude of gouty tophi.

show abstract

The Gouty Tophus: a Review

Cited by 114 publications

References 74 publications

Population-specific association between ABCG2 variants and tophaceous disease in people with gout

Population-specific association between ABCG2 variants and tophaceous disease in people with gout

Macrophage-derived IL-1β enhances monosodium urate crystal-triggered NET formation

Multiple Gouty Tophi with Bone Erosion and Destruction: A Report of an Early-onset Case in an Obese Patient

Contact Info

Product

Resources

About