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ObjectivesTo assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints.MethodsA web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises.ResultsThe web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification.ConclusionsBased on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined.

Background Gout is an inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystals’ joint deposition. MSU phagocytosis by resident macrophages is a key step in gout pathogenesis. MSU phagocytosis triggers nuclear factor kappa B (NFκB) activation and production of cytokines and chemokines. Proteoglycan-4 (PRG4) is a glycoprotein produced by synovial fibroblasts and exerts an anti-inflammatory effect in the joint mediated by its interaction with cell surface receptor CD44. PRG4 also binds and antagonizes TLR2 and TLR4. The objective of this study is to evaluate the efficacy of recombinant human PRG4 (rhPRG4) in suppressing MSU-induced inflammation and mechanical allodynia in vitro and in vivo. Methods THP-1 macrophages were incubated with MSU crystals ± rhPRG4 or bovine submaxillary mucin (BSM), and crystal phagocytosis, cytokines and chemokines expression and production were determined. NFκB p65 subunit nuclear translocation, NLRP3 induction, caspase-1 activation and conversion of proIL-1β to mature IL-1β were studied. MSU phagocytosis by Prg4 +/+ and Prg4 −/− peritoneal macrophages was determined in the absence or presence of rhPRG4, BSM, anti-CD44, anti-TLR2, anti-TLR4 and isotype control antibodies. Rhodamine-labeled rhPRG4 was incubated with murine macrophages and receptor colocalization studies were performed. Lewis rats underwent intra-articular injection of MSU crystals followed by intra-articular treatment with PBS or rhPRG4. Weight bearing and SF myeloperoxidase activities were determined. Results rhPRG4 reduced MSU crystal phagocytosis at 4 h ( p < 0.01 ) and IL-1β, TNF-α, IL-8 and MCP-1 expression and production at 6 h ( p < 0.05 ). BSM did not alter MSU phagocytosis or IL-1β production in human and murine macrophages. rhPRG4 treatment reduced NFκB nuclear translocation, NLRP3 expression, caspase-1 activation and generation of mature IL-1β ( p < 0.05 ). MSU-stimulated IL-1β production was higher in Prg4 −/− macrophages compared to Prg4 +/+ macrophages ( p < 0.001 ). rhPRG4, anti-CD44, anti-TLR2 and anti-TLR4 antibody treatments reduced MSU phagocytosis and IL-1β production in murine macrophages ( p < 0.05 ). rhPRG4 preferentially colocalized with CD44 on Prg4 −/− peritoneal macrophages compared to TLR2 or TLR4 ( p < 0.01 ). rhPRG4 normalized weight bearing and reduced SF myeloperoxidase activity compared to PBS in vivo. Conclusion rhPRG4 inhibits MSU crystal phagocytosis and exhibits an anti-inflammatory and anti-nociceptive activity in vitro and in vivo. rhPRG4’s anti-inflammatory mechanism may be due to targeting CD44 on macrophages.

The widespread adoption of digital health records, coupled with the rise of advanced diagnostic testing, has resulted in an explosion of patient data, comparable in scope to genomic datasets. This vast information repository offers significant potential for improving patient outcomes and decision-making, provided one can extract meaningful insights from it. This is where artificial intelligence (AI) tools like machine learning (ML) and deep learning come into play, helping us leverage these enormous datasets to predict outcomes and make informed decisions. AI models can be trained to analyze and interpret patient data, including physician notes, laboratory testing, and imaging, to aid in the management of patients with rheumatic diseases. As one of the most common autoimmune diseases, rheumatoid arthritis (RA) has attracted considerable attention, particularly concerning the evolution of diagnostic techniques and therapeutic interventions. Our aim is to underscore those areas where AI, according to recent research, demonstrates promising potential to enhance the management of patients with RA.

In this update on the genetics of hyperuricaemia and gout, the authors describe the associations between common genetic variants, serum uric acid levels and gout as well as the role of these genetic variants in gout pathogenesis. Pharmacogenetic associations between HLA-B * 5801 and severe allopurinol-hypersensitivity reactions and the potential causal role of urate in cardiovascular disease are also discussed. Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This Review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9 , ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular–metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B * 5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B * 5801 alleles could be used to predict these potentially fatal adverse effects. Key Points The majority of the genes that associate with hyperuricaemia and gout in genome-wide association studies have been implicated in the renal urate-transport system Genetic variation explains only a modest level of variance in serum uric acid levels (∼6%) Serum uric acid levels are determined by the net balance between urate absorption and secretion, which is mediated by separate sets of transporters in the renal proximal tubule The clinical utility of testing for urate-associated genes seems limited because serum urate levels themselves can effectively predict gout risk at a low cost Urate-associated genes and genetically determined urate levels have been largely unassociated with cardiovascular or metabolic outcomes, suggesting that serum uric acid does not have a causal role in these outcomes Strong pharmacogenetic associations between HLA-B * 5801 alleles and severe allopurinol-hypersensitivity reactions have been shown in Asian and European populations, suggesting clinical utility of testing for these alleles

Gout is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Researchers have recently made great advances in defining the pathogenesis of gout, including elucidating its risk factors and tracing the molecular mechanisms of renal urate transport and crystal-induced inflammation. Here, Choi et al investigate some key aspects of the pathogenesis og gout with a focus on the recent advances.

Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways.

Introduction Alopecia areata (AA) is the most common form of immune-mediated hair loss. Studies have begun to establish the most frequent comorbid diseases of AA; however, results have been inconsistent with few prospective studies. Methods A total of 63,692 women in the Nurses’ Health Study, 53–80 years, were prospectively followed from 2002 to 2014 to determine whether history of immune-mediated disease was associated with AA risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) for AA in relation to immune-mediated conditions were computed using Cox proportional hazard models, adjusted for AA risk factors. Results 133 AA cases were identified during follow-up. Personal history of any immune-mediated disease was associated with increased AA risk (HR 1.72, 95% CI 1.24–2.37). History of systemic lupus erythematosus (HR 5.43, 95% CI 2.11–13.97), multiple sclerosis (HR 4.10, 95% CI 1.40–11.96), vitiligo (HR 3.13, 95% CI 1.08–9.10), psoriasis (HR 2.01, 95% CI 1.00–4.03), hypothyroidism (HR 1.88, 95% CI 1.30–2.71), and rheumatoid arthritis (HR 1.66, 95% CI 1.09–2.52) were associated with increased AA risk. History of inflammatory bowel disease or Graves’ disease/hyperthyroidism was not significantly associated with AA risk. Conclusions In this prospective study, personal history of immune-mediated diseases either individually or overall was associated with increased AA risk.

Gout is a disorder of urate metabolism in which persistent high urate levels in the extracellular fluids result in the deposition of monosodium urate (MSU) crystal in joints and periarticular tissues. In recent years, this disease represents an increasingly common health problem, so the pace of investigation in the field has accelerated tremendously. New research advances in the pathogenesis of hyperuricemia and in the understanding of how MSU crystals induce an acute gouty attack have been focused in this review on the processes of inflammation and involvement of the innate immune response; in addition, we discuss new knowledge about the role of the reactive oxygen species in establishing oxidative stress in MSU crystal-induced arthritis.