Long-term stability of anti-cyclic citrullinated peptide antibody status in patients with early inflammatory polyarthritis.

INTRODUCTION: The utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, particularly in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed therefore to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP). METHODS: Anti-CCP and RF were measured at baseline and 5 years in 640 IP patients from the Norfolk Arthritis Register, a primary care-based inception cohort. The relation between change in anti-CCP status/titer and the presence of radiologic erosions, the extent of the Larsen score, and Health Assessment Questionnaire (HAQ) score by 5 years was investigated. RESULTS: With a cut-off of 5 U/ml, 28% subjects tested positive for anti-CCP antibodies, 29% for RF, and 21% for both at baseline. Nine (2%) anti-CCP-negative patients seroconverted to positive, and nine (4.6%) anti-CCP-positive individuals became negative between baseline and 5 years. In contrast, RF status changed in 17% of subjects. However, change in RF status was strongly linked to baseline anti-CCP status and was not independently associated with outcome. Ever positivity for anti-CCP antibodies by 5 years did not improve prediction of radiographic damage compared with baseline status alone (accuracy, 75% versus 74%). A higher baseline anti-CCP titer (but not change in anti-CCP titer) predicted worse radiologic damage at 5 years (P < 0.0001), even at levels below the cut-off for anti-CCP positivity. Thus, a titer of 2 to 5 U/ml was strongly associated with erosions by 5 years (odds ratio, 3.6 (1.5 to 8.3); P = 0.003). CONCLUSIONS: Repeated testing of anti-CCP antibodies or RF in patients with IP does not improve prognostic value and should not be recommended in routine clinical practice.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Identifying fire plumes in the Arctic with tropospheric FTIR measurements and transport models

We investigate Arctic tropospheric composition using ground-based Fourier transform infrared (FTIR) solar absorption spectra, recorded at the Polar Environment Atmospheric Research Laboratory (PEARL, Eureka, Nunavut, Canada, 80°05' N, 86°42' W) and at Thule (Greenland, 76°53' N, −68°74' W) from 2008 to 2012. The target species, carbon monoxide (CO), hydrogen cyanide (HCN), ethane (C_2H_6), acetylene (C_2H_2), formic acid (HCOOH), and formaldehyde (H_2CO) are emitted by biomass burning and can be transported from mid-latitudes to the Arctic. By detecting simultaneous enhancements of three biomass burning tracers (HCN, CO, and C_2H_6), ten and eight fire events are identified at Eureka and Thule, respectively, within the 5-year FTIR time series. Analyses of Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model back-trajectories coupled with Moderate Resolution Imaging Spectroradiometer (MODIS) fire hotspot data, Stochastic Time-Inverted Lagrangian Transport (STILT) model footprints, and Ozone Monitoring Instrument (OMI) UV aerosol index maps, are used to attribute burning source regions and travel time durations of the plumes. By taking into account the effect of aging of the smoke plumes, measured FTIR enhancement ratios were corrected to obtain emission ratios and equivalent emission factors. The means of emission factors for extratropical forest estimated with the two FTIR data sets are 0.40 ± 0.21 g kg^(−1) for HCN, 1.24 ± 0.71 g kg^(−1) for C_2H_6, 0.34 ± 0.21 g kg^(−1) for C_2H_2, and 2.92 ± 1.30 g kg^(−1) for HCOOH. The emission factor for CH_3OH estimated at Eureka is 3.44 ± 1.68 g kg^(−1). To improve our knowledge concerning the dynamical and chemical processes associated with Arctic pollution from fires, the two sets of FTIR measurements were compared to the Model for OZone And Related chemical Tracers, version 4 (MOZART-4). Seasonal cycles and day-to-day variabilities were compared to assess the ability of the model to reproduce emissions from fires and their transport. Good agreement in winter confirms that transport is well implemented in the model. For C_2H_6, however, the lower wintertime concentration estimated by the model as compared to the FTIR observations highlights an underestimation of its emission. Results show that modeled and measured total columns are correlated (linear correlation coefficient r > 0.6 for all gases except for H_2CO at Eureka and HCOOH at Thule), but suggest a general underestimation of the concentrations in the model for all seven tropospheric species in the high Arctic

Trends in the Vertical Distribution of Ozone: A Comparison of Two Analyses of Ozonesonde Data

We present the results of two independent analyses of ozonesonde measurements of the vertical profile of ozone. For most of the ozonesonde stations we use data that were recently reprocessed and reevaluated to improve their quality and internal consistency. The two analyses give similar results for trends in ozone. We attribute differences in results primarily to differences in data selection criteria and in utilization of data correction factors, rather than in statistical trend models. We find significant decreases in stratospheric ozone at all stations in middle and high latitudes of the northern hemisphere from 1970 to 1996, with the largest decreases located between 12 and 21 km, and trends of -3 to -10 %/decade near 17 km. The decreases are largest at the Canadian and the most northerly Japanese station, and are smallest at the European stations, and at Wallops Island, U.S.A. The mean mid-latitude trend is largest, -7 %/decade, from 12 to 17.5 km for 1970-96. For 1980-96, the decrease is more negative by 1-2 %/decade, with a maximum trend of -9 %/decade in the lowermost stratosphere. The trends vary seasonally from about 12 to 17.5 km, with largest ozone decreases in winter and spring. Trends in tropospheric ozone are highly variable and depend on region. There are decreases or zero trends at the Canadian stations for 1970-96, and decreases of -2 to -8 %/decade for the mid-troposphere for 1980-96; the three European stations show increases for 1970-96, but trends are close to zero for two stations for 1980-96 and positive for one; there are increases in ozone for the three Japanese stations for 1970-96, but trends are either positive or zero for 1980-96; the U.S. stations show zero or slightly negative trends in tropospheric ozone after 1980. It is not possible to define reliably a mean tropospheric ozone trend for northern mid-latitudes, given the small number of stations and the large variability in trends. The integrated column trends derived from the sonde data are consistent with trends derived from both surface based and satellite measurements of the ozone column

A roadmap to estimating agricultural ammonia volatilization over Europe using satellite observations and simulation data

Ammonia (NH3) is one of the most important gases emitted from agricultural practices. It affects air quality and the overall climate and is in turn influenced by long-term climate trends as well as by short-term fluctuations in local and regional meteorology. Previous studies have established the capability of the Infrared Atmospheric Sounding Interferometer (IASI) series of instruments, aboard the Metop satellites, to measure ammonia from space since 2007. In this study, we explore the interactions between atmospheric ammonia, land and meteorological variability, and long-term climate trends in Europe. We investigate the emission potential (Γsoil) of ammonia from the soil, which describes the soil–atmosphere ammonia exchange. Γsoil is generally calculated in-field or in laboratory experiments; here, and for the first time, we investigate a method which assesses it remotely using satellite data, reanalysis data products, and model simulations. We focus on ammonia emission potential in March 2011, which marks the start of growing season in Europe. Our results show that Γsoil ranges from 2 × 103 to 9.5 × 104 (dimensionless) in fertilized cropland, such as in the North European Plain, and is of the order of 10–102 in a non-fertilized soil (e.g., forest and grassland). These results agree with in-field measurements from the literature, suggesting that our method can be used in other seasons and regions in the world. However, some improvements are needed in the determination of mass transfer coefficient k (m s−1), which is a crucial parameter to derive Γsoil. Using a climate model, we estimate the expected increase in ammonia columns by the end of the century based on the increase in skin temperature (Tskin), under two different climate scenarios. Ammonia columns are projected to increase by up to 50 %, particularly in eastern Europe, under the SSP2-4.5 scenario and might even double (increase of 100 %) under the SSP5-8.5 scenario. The increase in skin temperature is responsible for a formation of new hotspots of ammonia in Belarus, Ukraine, Hungary, Moldova, parts of Romania, and Switzerland.</p

Genetic variation in FOXO3 is associated with reductions in inflammation and disease activity in inflammatory polyarthritis

OBJECTIVE: Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte-driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. METHODS: Collagen-induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss-of-function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C-reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. RESULTS: Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin-6 in the blood. Similarly, rs12212067 (a single-nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. CONCLUSION: Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage

SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA

A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis

Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)- DRB1 locus that possesses the shared susceptibility epitope (SE) and the citrullination of self-antigens. We show how citrullinated aggrecan and vimentin epitopes bind to HLADRB1* 04:01/04. Citrulline was accommodated within the electropositive P4 pocket of HLA-DRB1*04:01/04, whereas the electronegative P4 pocket of the RA-resistant HLADRB1* 04:02 allomorph interacted with arginine or citrulline-containing epitopes. Peptide elution studies revealed P4 arginine-containing peptides from HLA-DRB1*04:02, but not from HLA-DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin, thereby generating self-epitopes that are presented to T cells in HLA-DRB1*04:01+ individuals. Using HLA-II tetramers, we observed citrullinated vimentin- and aggrecan-specific CD4+ T cells in the peripheral blood of HLA-DRB1*04:01+ RA-affected and healthy individuals. In RA patients, autoreactive T cell numbers correlated with disease activity and were deficient in regulatory T cells relative to healthy individuals. These findings reshape our understanding of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in RA

Analysis of SNP-SNP interactions and bone quantitative ultrasound parameter in early adulthood

Background: Osteoporosis individual susceptibility is determined by the interaction of multiple genetic variants and environmental factors. The aim of this study was to conduct SNP-SNP interaction analyses in candidate genes influencing heel quantitative ultrasound (QUS) parameter in early adulthood to identify novel insights into the mechanism of disease. Methods: The study population included 575 healthy subjects (mean age 20.41; SD 2.36). To assess bone mass QUS was performed to determine Broadband ultrasound attenuation (BUA, dB/MHz). A total of 32 SNPs mapping to loci that have been characterized as genetic markers for QUS and/or BMD parameters were selected as genetic markers in this study. The association of all possible SNP pairs with QUS was assessed by linear regression and a SNP-SNP interaction was defined as a significant departure from additive effects. Results: The pairwise SNP-SNP analysis showed multiple interactions. The interaction comprising SNPs rs9340799 and rs3736228 that map in the ESR1 and LRP5 genes respectively, revealed the lowest p value after adjusting for confounding factors (p-value = 0.001, β (95% CI) = 14.289 (5.548, 23.029). In addition, our model reported others such as TMEM135-WNT16 (p = 0.007, β(95%CI) = 9.101 (2.498, 15.704), ESR1-DKK1 (p = 0.012, β(95%CI) = 13.641 (2. 959, 24.322) or OPG-LRP5 (p = 0.012, β(95%CI) = 8.724 (1.936, 15.512). However, none of the detected interactions remain significant considering the Bonferroni significance threshold for multiple testing (p<0.0001). Conclusion: Our analysis of SNP-SNP interaction in candidate genes of QUS in Caucasian young adults reveal several interactions, especially between ESR1 and LRP5 genes, that did not reach statistical significance. Although our results do not support a relevant genetic contribution of SNP-SNP epistatic interactions to QUS in young adults, further studies in larger independent populations would be necessary to support these preliminary findings.This study was supported by a grant PI-0414-2014 from Consejería de Salud (Junta de Andalucía, Spain). Correa-Rodríguez M is a predoctoral fellow (FPU13/ 00143) from the Ministerio de Educación, Cultura y Deporte (Programa de Formación del Profesorado Universitario)

Comparisons of the Orbiting Carbon Observatory-2 (OCO-2) XCO2_{CO_{2}} measurements with TCCON

NASA\u27s Orbiting Carbon Observatory-2 (OCO-2) has been measuring carbon dioxide column-averaged dry-air mole fraction, X$_{CO_{2}}$, in the Earth\u27s atmosphere for over 2 years. In this paper, we describe the comparisons between the first major release of the OCO-2 retrieval algorithm (B7r) and X$_{CO_{2}}$ from OCO-2\u27s primary ground-based validation network: the Total Carbon Column Observing Network (TCCON). The OCO-2 X$_{CO_{2}}$ retrievals, after filtering and bias correction, agree well when aggregated around and coincident with TCCON data in nadir, glint, and target observation modes, with absolute median differences less than 0.4 ppm and RMS differences less than 1.5 ppm. After bias correction, residual biases remain. These biases appear to depend on latitude, surface properties, and scattering by aerosols. It is thus crucial to continue measurement comparisons with TCCON to monitor and evaluate the OCO-2 X$_{CO_{2}}$ data quality throughout its mission