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Gout Urate Cryst. Depos. Dis., Volume 2, Issue 2 (June 2024) – 4 articles

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11 pages, 3813 KiB  
Brief Report
Sex-Specific Differences in Cytokine Production Capacity in Patients with Gout Compared to Controls
by Medeea Badii, Orsolya I. Gaal, Ioana Hotea, Valentin Nica, Andreea M. Mirea, Dragoş Mărginean, HINT Consortium, Cristina Pamfil, Simona Rednic, Radu A. Popp, Tania O. Crişan and Leo A. B. Joosten
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 133-143; https://doi.org/10.3390/gucdd2020012 - 22 Apr 2024
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Abstract
Gout, an inflammatory disease orchestrated by interleukin-1β activation and release, is more prevalent in men. The clinical profiles of patients with gout report differences by sex. This study aims to investigate sex-specific cytokine profiles in circulation and in stimulated peripheral blood mononuclear cells [...] Read more.
Gout, an inflammatory disease orchestrated by interleukin-1β activation and release, is more prevalent in men. The clinical profiles of patients with gout report differences by sex. This study aims to investigate sex-specific cytokine profiles in circulation and in stimulated peripheral blood mononuclear cells (PBMCs) of patients with gout and controls. Participants included in the gout group met the criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR). The control group included individuals with varying levels of serum urate and absence of gout. PBMCs were stimulated in vitro for 24 h with various TLR ligands. Cytokines were determined in culture supernatants and plasma. Plasma IL-1Ra and high-sensitivity C-reactive protein (hsCRP) were higher in men with gout compared to men without gout whereas no significant differences in circulating cytokines were observed in women. PBMCs of patients with gout showed higher cytokine production of IL-1β, IL-1Ra, and TNF-α following 24 h stimulation, predominantly observed in women. We identified sex-specific cytokine production in gout in response to in vitro stimulation. While men with gout had higher levels of circulating cytokines, stimulated PBMCs of women with gout show an enhanced capacity for cytokine production. These data may suggest potentially different regulatory mechanisms of inflammation in men and women with gout. Full article
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25 pages, 1161 KiB  
Review
Circadian Rhythms in NLRP3 Inflammasome Regulation: Possible Implications for the Nighttime Risk of Gout Flares
by Raewyn C. Poulsen and Nicola Dalbeth
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 108-132; https://doi.org/10.3390/gucdd2020011 - 15 Apr 2024
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Abstract
Gout flares more frequently start late at night or in the early morning compared to during the day. The reasons for this are unknown. Activation of the NLRP3 inflammasome in monocytes/macrophages is central to initiation of gout flares. Here, we review the mechanisms [...] Read more.
Gout flares more frequently start late at night or in the early morning compared to during the day. The reasons for this are unknown. Activation of the NLRP3 inflammasome in monocytes/macrophages is central to initiation of gout flares. Here, we review the mechanisms by which circadian clocks control the NLRP3 inflammasome and the implications of this for the nighttime pattern of gout flares. Several hormones involved in inflammation regulation, e.g., glucocorticoids, melatonin and melanocortins, are under circadian control, with both circulating hormone levels as well as the expression of their receptors on target tissues showing time-of day differences. In addition, the NLRP3 inflammasome is also under the control of the macrophage circadian clock, leading to time-of-day differences in expression of NLRP3 inflammasome components and susceptibility to inflammasome-activating stimuli. MSU crystal exposure leads to altered expression of circadian clock components in macrophages, leading to time-of-day-specific loss of repression of NLRP3 inflammasome activity. Taken together, there is clear evidence that circadian clocks regulate the NLRP3 inflammasome and that this regulation may be compromised by MSU crystal exposure in gout. Circadian control of the inflammasome may be one of the factors contributing to nighttime susceptibility to gout flares. Full article
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7 pages, 230 KiB  
Review
Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review
by Augustin Latourte, Hang-Korng Ea and Pascal Richette
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 101-107; https://doi.org/10.3390/gucdd2020010 - 05 Apr 2024
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Abstract
Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition [...] Read more.
Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising. Full article
15 pages, 3588 KiB  
Review
Optimising the Use of Ultrasound in Gout: A Review from the Ground Up
by Emilio Filippucci, Edoardo Cipolletta, Silvia Sirotti and Georgios Filippou
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 86-100; https://doi.org/10.3390/gucdd2020009 - 04 Apr 2024
Viewed by 347
Abstract
The use of ultrasonography (US) has considerable potential for the diagnosis and monitoring of gout due to its capacity to detect monosodium urate deposits. In the last decade, a critical amount of scientific data has become available. Consensus-based definitions for ultrasonographic elementary lesions [...] Read more.
The use of ultrasonography (US) has considerable potential for the diagnosis and monitoring of gout due to its capacity to detect monosodium urate deposits. In the last decade, a critical amount of scientific data has become available. Consensus-based definitions for ultrasonographic elementary lesions in gout have been developed, tested, and validated, as well as a semiquantitative scoring system for their quantification. Many scanning protocols have been proposed in different clinical scenarios. In this review, we formulate a set of practical suggestions for the use of the US in daily practice. We discuss the current knowledge to indicate which joints and structures are to be scanned and which elementary findings are to be evaluated according to the clinical scenario. While for some clinical settings, a quite definite scanning protocol can be indicated, others still need to be further investigated, and how to obtain the best out of the US is still entrusted to the individual experience. Full article
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