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Abstract: Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long‐term urate‐lowering treatment. Urate‐lowering drugs should be used during the inter‐critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate‐lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a nationwide cohort study to investigate the relationship between systemic lupus erythematosus (SLE) and the risk of incident respiratory failure. Methods: From the National Health Insurance Research Database, we identified 11 533 patients newly diagnosed with SLE and 46 132 controls without SLE who were randomly selected through frequency-matching according to age, sex, and index year. Both cohorts were followed until the end of 2011 to measure the incidence of incident respiratory failure, which was compared between the 2 cohorts through a Cox proportional hazards regression analysis. Results: The adjusted hazard ratio (aHR) of incident respiratory failure was 5.80 (95% confidence interval [CI] = 5.15–6.52) for the SLE cohort after we adjusted for sex, age, and comorbidities. Both men (aHR = 3.44, 95% CI = 2.67–4.43) and women (aHR = 6.79, 95% CI = 5.93–7.77) had a significantly higher rate of incident respiratory failure in the SLE cohort than in the non-SLE cohort. Both men and women aged <35 years (aHR = 31.2, 95% CI = 21.6–45.2), 35–65 years; (aHR = 6.19, 95% CI = 5.09–7.54) and ≥65 years (aHR = 2.35, 95% CI = 1.92–2.87) had a higher risk of incident respiratory failure in the SLE cohort. Moreover, the risk of incident respiratory failure was higher in the SLE cohort than the non-SLE cohort, for subjects with (aHR = 2.65, 95% CI = 2.22–3.15) or without (aHR = 9.08, 95% CI = 7.72–10.7) pre-existing comorbidities. In the SLE cohort, subjects with >24 outpatient visits and hospitalizations per year had a higher incident respiratory failure risk (aHR = 21.7, 95% CI = 18.0–26.1) compared with the non-SLE cohort. Conclusion: Patients with SLE are associated with an increased risk of incident respiratory failure, regardless of their age, sex, and pre-existing comorbidities; especially medical services with higher frequency. [ABSTRACT FROM AUTHOR]

Objectives: An increased risk of mortality in patients with hyperuricemia has been reported. We examined (1) the risk of all-cause and cardiovascular disease (CVD) mortality in untreated hyperuricemic patients who did not receive urate-lowering therapy (ULT), and (2) the impact of ULT on mortality risk in patients with hyperuricemia. Methods: In this retrospective case-matched cohort study during a mean follow-up of 6.4 years, 40,118 Taiwanese individuals aged ≥17 years who had never used ULT and who had never had gout were examined. The mortality rate was compared between 3,088 hyperuricemic patients who did not receive ULT and reference subjects (no hyperuricemia, no gout, no ULT) matched for age and sex (1:3 hyperuricemic patients/reference subjects), and between 1,024 hyperuricemic patients who received ULT and 1,024 hyperuricemic patients who did not receive ULT (matched 1:1 based on their propensity score and the index date of ULT prescription). Cox proportional hazard modeling was used to estimate the respective risk of all-cause and CVD (ICD-9 code 390–459) mortality. Results: After adjustment, hyperuricemic patients who did not receive ULT had increased risks of all-cause (hazard ratio, 1.24; 95% confidence interval, 0.97–1.59) and CVD (2.13; 1.34–3.39) mortality relative to the matched reference subjects. Hyperuricemic patients treated with ULT had a lower risk of all-cause death (0.60; 0.41–0.88) relative to hyperuricemic patients who did not receive ULT. Conclusion: Under-treatment of hyperuricemia has serious negative consequences. Hyperuricemic patients who received ULT had potentially better survival than patients who did not. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chronic inflammation that triggers endothelial dysfunction and atherosclerosis may promote the evolution of cardiovascular diseases, including acute ischemic stroke (AIS). In this study, we assessed the association between rhinitis (RN), an immunoglobulin E-related atopic disease, and the risk of AIS. Methods: We used a Taiwan national insurance claims data set of 1 million enrollees to distinguish 61,899 patients with RN and 123,798 randomly selected age- and sex-matched controls from January 1, 2000, to December 31, 2010. Both cohorts were followed up until the occurrence of stroke or the end of follow-up. The risk of AIS was evaluated by using the Cox proportional hazards regression model. Results: After adjustment of the relevant covariates, the RN group showed a lower risk of AIS (adjusted hazard ratio [aHR] 0.74 [95% confidence interval {CI}, 0.70-0.79]) compared with the control cohort at the end of follow-up. Among the participants without comorbidities, the RN cohort still had a lower risk of AIS compared with the control cohort (aHR 0.69 [95% CI, 0.59-0.81]). Moreover, in the three stratified age groups, RN was associated with a significantly decreased risk of AIS (ages ≤49 years: aHR 0.77 [95% CI, 0.63-0.95]; ages 50-64 years: aHR 0.72 [95% CI, 0.64-0.81]; ages ≥65 years: aHR 0.78 [95% CI, 0.71-0.85]). Conclusions: RN was associated with a decreased risk of developing AIS. Although a reduction in risk of AIS was observed, it warrants further consideration to prevent AIS in patients with RN. [ABSTRACT FROM AUTHOR]

Background: High serum uric acid (sUA) has been associated with increased mortality risks, but its clinical treatment varied with potential side effects. The role of physical activity has received limited attention.Methods: A cohort, consisting of 467 976 adults, who went through a standard health screening programme, with questionnaire and fasting blood samples, was successively recruited between 1996 and 2008. High sUA is defined as uric acid above 7.0 mg/dL. Leisure time physical activity level was self-reported, with fully active defined as those with 30 min per day for at least 5 days a week. National death file identified 12 228 deaths with a median follow-up of 8.5 years. Cox proportional model was used to analyse HRs, and 12 variables were controlled, including medical history, life style and risk factors.Findings: High sUA constituted one quarter of the cohort (25.6%). Their all-cause mortality was significantly increased [HR: 1.22 (1.15-1.29)], with much of the increase contributed to by the inactive (HR: 1.27 (1.17-1.37)), relative to the reference group with sUA level of 5-6 mg/dL. When they were fully active, mortality risks did not increase, but decreased by 11% (HR: 0.89 (0.82-0.97)), reflecting the benefits of being active was able to overcome the adverse effects of high sUA. Given the same high sUA, a 4-6 years difference in life expectancy was found between the active and the inactive.Conclusions: Physical activity is a valuable alternative to pharmacotherapy in its ability to reduce the increases in mortality risks from high sUA. By being fully active, exercise can extend life span by 4-6 years, a level greater than the 1-4 years of life-shortening effect from high sUA. [ABSTRACT FROM AUTHOR]

Objectives: Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia. Methods: We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0–729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling. Results: Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 103 person-years) and reference subjects (n = 15,162; 9.26 per 103 person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61–1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43–1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity). Conclusions: Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia. [ABSTRACT FROM AUTHOR]

The number of people with asthma has dramatically increased over the past few decades and the cost of care is more than $11·3 billion per year. The use of steroids is the major treatment to control asthma symptoms, but the side effects are often devastating. Seeking new drugs or new strategies to reduce the dose of steroid taken has always been an important task. A bovine whey protein extract (WPE), which is enriched in transforming growth factor-β (TGF-β), has been demonstrated to have the potential for reducing symptoms associated with mild-to-moderate T-helper cell type 1-mediated psoriasis in human subjects. However, whether WPE also has potential for inhibiting T-helper cell type 2 (Th2)-mediated disease remains unclear. In the present study, using a murine asthma model, we found that sensitised mice fed WPE daily, before they were challenged, resulted in reducing airway inflammation, serum ovalbumin-specific IgE, Th2-related cytokine production and airway hyperresponsiveness. Increase in the regulatory T cell (Treg) population in vitro and in vivo was observed when treated with WPE. According to the results from the TGF-β-blocking antibody study, we suggest that TGF-β is the main component that endows WPE with the potential to reduce the generation of Treg. Thus, the present data suggest that WPE has the potential to alleviate the symptoms of asthma by inducing the generation of Treg. Therefore, regular administration of WPE might be potentially beneficial for patients with asthma. [ABSTRACT FROM PUBLISHER]

Objective Hyperuricemia is the most important risk factor for the development of gout; however, not all patients with hyperuricemia develop gout, and patients experiencing a gout attack are not necessarily found to have hyperuricemia. We hypothesized that the interactions between serum uric acid (sUA) and other potential metabolic comorbidities increase the risk of gout development. Methods A prospective study was conducted to link baseline metabolic profiles from the MJ Health Screening Center to gout outcomes extracted from the Taiwan National Health Insurance database. A Cox proportional hazards model was used to assess the metabolic risks for incident gout stratified by hyperuricemia status (sUA level >7 mg/dl or not). Results During a mean followup period of 6.45 years (261,500 person-years), 1,189 patients with clinical gout (899 men, 202 women ages >50 years, and 88 women ages ≤50 years) were identified among the 40,513 examinees. The multivariate adjusted hazard ratios (HRs) of hyperuricemia for gouty arthritis were 5.80 (95% confidence interval [95% CI] 4.93-6.81) in men and 4.37 (95% CI 3.38-5.66) in women. Hypertriglyceridemia (triglyceride level >150 mg/dl) was found as an independent risk factor, with HRs of 1.38 (95% CI 1.18-1.60) in men with hyperuricemia and 1.40 (95% CI 1.02-1.92) in men without hyperuricemia. General obesity (body mass index >27 kg/m2) was independently associated with gout in older women, with HRs of 1.72 (95% CI 1.15-2.56) in women with hyperuricemia and 2.19 (95% CI 1.47-3.26) in women without hyperuricemia. Conclusion General obesity in women and hypertriglyceridemia in men may potentiate an sUA effect for gout development. Further investigation is needed. [ABSTRACT FROM AUTHOR]

Abstract: Aims: There is an ongoing discussion on whether serum uric acid (SUA) predicts ischemic heart disease (IHD) independently of other metabolic factors, which, if confirmed, would signify a role for uric acid in the pathogenesis of cardiovascular disease. We investigated whether such a relation exists for ethnic Chinese with low CVD risk. Methods and results: Enrolled, between 1994 and 1996, were 128,569 adults ≥20years from four ‘MJ’ Health Check-up Clinics in Taiwan. Excluded were those with heart disease, previous stroke(s), renal disease, and/or cancer. Physical examinations, biospecimen collections, and structured questionnaires were executed according to standardised protocols. We identified IHD events according to the ICD-9-CM codes 410–414 using hospitalisation records obtained from the National Health Insurance and the Death Certification Registry databases. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) between SUA and IHD events. A total of 2049 subjects (1239 men, 810 women) developed IHD from baseline to Dec. 31, 2002. Men had a higher IHD incidence than did women (2.84 vs. 1.61 1/1000person-years; p<0.0001). The risk-factor-adjusted HRs (95% confidence-interval [CI]) for hyperuricemiae (SUA ≥7.0/≥6.0mg/dL) were 1.25 (1.11–1.40) for men and 1.19 (1.02–1.38) for women. In the low-risk population (lacking the NCEP-ATPIII metabolic syndrome components), a significant association was still observed (adjusted HR: 1.54 [1.09–2.17]). Conclusion: The hyperuricemia was independently associated with the development of IHD not only in the general population but also in those without any metabolic risk factor for NCEP ATPIII. Hyperuricemia may be considered as a potential risk factor for IHD. [Copyright &y& Elsevier]

Objective: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard., Methods: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout., Results: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62])., Conclusion: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi., Competing Interests: AO has received consulting fees from Novartis. ND has received consulting fees, speaker fees or grants from the following companies: Takeda, Menarini, Teijin, Pfizer, Crealta, Cymabay, Fonterra, Ardea Biosciences and AstraZeneca, outside the submitted work. WT has received consulting fees from AstraZeneca and Pfizer. FPR has received consulting fees from AstraZeneca, Menarini and Cymabay; speaker fees from AstraZeneca and Menarini; investigation grants from Spanish Health Ministry, Basque Country Industry and Development Department, Spanish Foundation for Rheumatology, and Cruces Hospital Rheumatology Association. LKS has received consulting fees from AstraZeneca. AKT has received fees from Berlin-Chemie Menarini, Andrea Biosciences/AstraZeneca and Novartis. GM has received consulting and speaker fees from Menarini. MAC has received investigation grants and speakers fees from Menarini., (© 2016, American College of Rheumatology.)

Objective: To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies., Methods: Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard., Results: For all tested GUGC definitions, the simple definition of "self-report of gout or urate-lowering therapy use" had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%)., Conclusion: A simple definition of "self-report of gout or urate-lowering therapy use" has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered., (© 2016, American College of Rheumatology.)

Background: The association between the risk of subsequent gout and hypertensive disorders in pregnancy (HDP), including gestational hypertension and preeclampsia has not been well investigated. We investigated the risk of gout in later life for women with a history of HDP., Methods: We identified 1133 newly diagnosed HDP women aged 14-40 years from Taiwan insurance claims data from the period of 2000-2010. From the same database, 9064 women without HDP were randomly selected as the control cohort, with frequency matched by age and diagnosis year. Those with a baseline history of hypertension or gout were excluded from this study. All study participants were followed until the development of gout, withdrawal from the insurance program, or the end of 2011. Cox proportional hazards regression was used to assess the risk for gout in the HDP cohort compared with the controls., Results: The incidence of gout was 2.83 folds higher in the HDP cohort than in the control cohort (2.66 vs. 0.94 per 1000 person-years) with an adjusted hazard ratio of 2.34 (95% confidence interval = 1.36-4.02) and 1.84 (95% confidence interval = 1.03-3.32) after controlling for comorbidities prior to and after pregnancy, respectively. In addition, the risk for gout increased as the severity of HDP increased., Conclusion: Women with HDP are at higher risk of developing gout in their later life. Close surveillance for hyperuricemia and lifestyle intervention should be considered for these high risk women. Further prospective study is needed for investigating the relationship between HDP and subsequent gout.

Objective: To determine the frequency of adverse events of diagnostic arthrocentesis in patients with possible gout., Methods: Consecutive patients underwent arthrocentesis and were evaluated at 6 weeks to determine adverse events. The 95% CI were obtained by bootstrapping., Results: Arthrocentesis was performed in 910 patients, and 887 (97.5%) were evaluated for adverse events. Any adverse event was observed in 12 participants (1.4%, 95% CI 0.6-2.1). There was 1 case (0.1%, 95% CI 0-0.34) of septic arthritis., Conclusions: Diagnostic arthrocentesis is associated with a low frequency of adverse events. Septic arthritis rarely occurs.

Objective: To examine (1) the risk of death from cardiovascular disease (CVD) and from all causes in patients with gout who do not undergo urate-lowering therapy (ULT), and (2) the effect of ULT on mortality risk in patients with gout., Methods: In this prospective case-matched cohort study, 40,623 Taiwanese individuals aged ≥ 17 years were followed for 6.5 years. Mortality rate was compared between 1189 patients with gout who did not receive ULT and reference subjects (no gout, no ULT) matched for age, sex, and the index date of gout diagnosis (1:3 patients with gout/reference subjects), and between 764 patients with gout who received ULT and 764 patients with gout who did not receive ULT matched 1-to-1 based on their propensity score and the index date of ULT prescription. Cox proportional hazard modeling was used to estimate the respective risk of CVD (International Classification of Diseases, 9th ed. code 390-459) and all-cause mortality., Results: After adjustment, patients with gout not treated with ULT had an increased risk of CVD mortality (HR 2.43, 95% CI 1.33-4.45) and all-cause mortality (1.45, 1.05-2.00) relative to the matched reference subjects (no gout, no ULT). Patients with gout treated with ULT had a lower risk of CVD (0.29, 0.11-0.80) and all-cause mortality (0.47, 0.29-0.79) relative to patients with gout not treated with ULT. This survival benefit persisted for users of either allopurinol or benzbromarone., Conclusion: Patients with gout who received ULT had significantly better survival rates than those who did not. Thus, undertreatment of gout has serious negative consequences.

Objective: To determine which clinical, laboratory, and imaging features most accurately distinguished gout from non-gout., Methods: We performed a cross-sectional study of consecutive rheumatology clinic patients with ≥1 swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (two-thirds) and test sample (one-third). Univariate and multivariate association between clinical features and monosodium urate-defined gout was determined using logistic regression modeling. Shrinkage of regression weights was performed to prevent overfitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement., Results: In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n = 653), the following features were selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13), difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved (multivariate OR 2.30), location of currently tender joints in other foot/ankle (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6 mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49). The final model performed adequately in the test set, with no evidence of misfit, high discrimination, and predictive ability. MTP1 joint involvement was the most common joint pattern (39.4%) in gout cases., Conclusion: Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria., (© 2015, American College of Rheumatology.)

Introduction: Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied., Methods: Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect TG2 expression in synovial fluid mononuclear cells (SFMCs) and synovial tissue from patients with gouty arthritis. MSU crystal-exposed RAW264.7 mouse macrophages were analyzed for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and TG2 expression by RT-PCR and enzyme-linked immunosorbent assay (ELISA). TG2 small interfering (si)-RNA-mediated silencing and overexpression in RAW264.7 cells were used to evaluate the involvement of TG2 in resolving MSU crystal-induced inflammation. The role of metastatic tumor antigen 1 (MTA1), a master chromatin modifier, was investigated by MTA1 si-RNA-mediated knockdown. In addition, the inflammatory responses were followed in wild type and TG2 null mice after being challenged with MSU crystals in an in vivo peritonitis model., Results: TG2 expression was up-regulated in the synovium tissue and SFMCs from patients with gouty arthritis. The levels of MTA1, TG2, TGF-β1, IL-1β and TNF-α mRNAs were consistently increased in MSU crystal-stimulated RAW264.7 cells. si-MTA1 impaired the basal, as well as the MSU crystal-induced expression of TG2 and TGF-β1, but increased that of IL-1β and TNF-α. TG2 overexpression dramatically suppressed MSU crystal-induced IL-1β and TNF-α, but significantly enhanced the TGF-β1 production. Neutralizing TGF-β antibodies or inhibition of the crosslinking activity of TG2 attenuated these effects. On the contrary, loss of TG2 resulted in a reduced TGF-β, but in an increased IL-1β and TNF-α production in MSU crystal-stimulated RAW264.7 cells and mouse embryonic fibroblasts (MEFs). MSU crystal-stimulated IL-1β production was Janus kinase 2 (JAK2)-signaling dependent and TG2-induced TGF-β suppressed the activity of it. Finally, TG2-deficient mice exhibited hyper inflammatory responses after being challenged with MSU crystals in an in vivo peritonitis model., Conclusions: These findings reveal an inherent regulatory role of the MTA1-TG2 pathway in the self-limitation of MSU crystal-induced inflammation via positively regulating the levels of active TGF-β1 in macrophages that opposes the MSU crystal-induced JAK2-dependent pro-inflammatory cytokine formation.

Objective: To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout., Methods: Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index., Results: Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory., Conclusion: Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.

We observed by flow cytometry that the frequency of both gastric infiltrating Tregs and PD-1-positive CD4 T cells is correlated with the density of Helicobacter pylori, suggesting that cellular immunity against this pathogen is inhibited.