Artrite Reumatoide e a Poluição do Ar

A artrite reumatoide é uma doença inflamatória, crônica, autoimune, sistêmica e progressiva com etiologia ainda desconhecida, que causa danos progressivos ao sistema musculoesquelético. Esta doença atinge aproximadamente 0,5% a 1% da população mundial, predomina no sexo feminino e acomete todas as faixas etárias com maior prevalência entre 40-60 anos. A atividade da doença é avaliada pelo Índice de Atividade da Doença (DAS28) analisando 28 articulações. Estudos demonstram que a poluição atmosférica está associada aos agravos à saúde humana e à perda de qualidade de vida. Este estudo teve como objetivo relatar o papel da poluição atmosférica na artrite reumatoide, através de uma revisão narrativa de literatura, a partir das bases de dados PubMed e Scielo. Incluíram-se artigos nos idiomas inglês e português publicados em periódicos, nacionais e internacionais, acerca da temática da pesquisa. A relação entre o desenvolvimento da AR e diferentes poluentes atmosféricos foi analisada em diversos estudos, que demostraram associação entre diferentes poluentes atmosféricos e o desenvolvimento da doença, no entanto, nenhum estudo publicado até a data atual, avaliou a relação com a exacerbação da atividade da doença. Palavras-chave: Artrite Reumatoide. Poluição do Ar. Doenças Autoimunes. Abstract Rheumatoid arthritis is an inflammatory, chronic, autoimmune, systemic and progressive disease with a still unknown etiology that causes progressive damage to the musculoskeletal system. This disease affects approximately 0.5% to 1% of the world population, predominates in females and affects all age groups with a higher prevalence between 40-60 years. The disease activity is assessed by the Disease Activity Index (DAS28) analyzing 28 joints. Studies show that air pollution is associated with damage to human health and loss of quality of life. This study aimed to report the role of air pollution in rheumatoid arthritis, through a literature narrative review, using the PubMed and Scielo databases. Articles in English and Portuguese published in national and international journals about the research theme were included. The relationship between the RA development and different air pollutants has been analyzed in several studies, which showed an association between different air pollutants and the development of the disease, however, no study published to date has evaluated the relationship with the disease activity exacerbation. Keywords: Rheumatoid Arthritis. Air Pollution. Autoimmune Diseases.

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AB0229 SHORT-TERM EXPOSURE TO OUTDOOR AIR POLLUTANTS AND RHEUMATOID ARTHRITIS ACTIVITY IN METROPOLITAN AREAS IN THE NORTH OF ITALY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2757 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1415.1-1415

Author(s):

F. Ingegnoli ◽

T. Ubiali ◽

T. Schioppo ◽

V. Longo ◽

S. Iodice ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Air Pollution ◽

Disease Activity ◽

Air Pollutants ◽

Positive Trend ◽

Inverse Association ◽

Short Term ◽

Short Term Exposure ◽

The Impact

Background:Air pollution is believed to cause oxidative stress and systemic inflammation, that could trigger autoimmunity in rheumatoid arthritis (RA). Several epidemiological studies investigated the possible role of air pollution in the outbreak of RA with controversial results. As far as we know, studies on the effects on disease activity of short-term exposure have not been published.Objectives:To evaluate the impact of short-term exposure to air pollutants (daily mean PM10, PM2.5, NO2and O3) on disease activity in patients with RA.Methods:Consecutive patients with RA (ACR/EULAR Criteria 2010) resident in Lombardy (Italy) were enrolled. In each patient Disease Activity Score on 28 joints (DAS28), Simple Disease Activity Index (SDAI) were assessed. Daily PM10, PM2.5, NO2and O3concentrations, estimated by Regional Environmental Protection Agency at municipality resolution, were used to assign short-term exposure from day of visit back to 14 days. Multivariable linear regression models were performed to identify the day of the pollutants independently associated with disease activity indices, adjusting for the variables significant at the univariate analysis. β coefficients were reported for 1 μg/m3increments of pollutants’ concentrations.Results:422 RA patients were enrolled in the study between January and June 2018: 81.5% females, mean age 58.2±13.3 years, mean disease duration 16.1±11.5 years, 27.3% current smokers, 59.5% RF positivity, 54.5% ACPA positivity. Sparse punctual statistically significant negative associations emerged at the multivariate analysis between PM10, PM2.5, NO2and the outcomes, although with very low estimates, whereas positive associations resulted for O3.Afterwards patients were stratified in 3 subgroups according to their ongoing treatment (no therapy, n=25, conventional synthetic Disease Modifying anti-Rheumatic Drugs -DMARDs-, n=108 and biological or targeted synthetic DMARDs, n=289). A statistical significance was found by analysing the influence of therapy on the interaction between PM2.5and DAS28 (Figure below): a positive trend between PM2.5and DAS28 appeared in the first two groups (no therapy, 0.013±0.007, p=0.06 and csDMARDs, 0.006±0.004, p=0.17), whereas a statistically significant inverse association was seen in the b/tsDMARDs group (-0.005±0.002, p=0.01). Therapy interaction was particularly evident in several days before the visit also for O3.Conclusion:The changes of the outcome measures related to the increase of the pollutants’ levels did not reach the minimal clinically important difference, therefore air pollution seems barely relevant on disease activity once the loss of tolerance is established in RA. O3and PM/NO2always exhibit an opposite performance having inversely proportional atmospheric concentrations, whereas the biological role of this substance is still matter of debate and will need further understanding. Therapy seems to be able to interact with the relation between air pollutants and the parameters considered.Disclosure of Interests:Francesca Ingegnoli: None declared, Tania Ubiali: None declared, Tommaso Schioppo: None declared, Valentina Longo: None declared, Simona Iodice: None declared, Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Orazio De Lucia: None declared, Antonella Murgo: None declared, Valentina Bollati: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

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Anemia e índices de atividade de doença em mulheres com artrite reumatoide

Scientia Medica ◽

10.15448/1980-6108.2018.2.28816 ◽

2018 ◽

Vol 28 (2) ◽

pp. 28816

Author(s):

Thamiris Becker Scheffel ◽

Aline Defaveri do Prado ◽

Henrique Luiz Staub ◽

Inês Guimarães da Silveira ◽

Ana Lígia Bender

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Health Assessment ◽

Disease Activity Index ◽

Significant Negative Correlation ◽

Cross Sectional Study ◽

Cross Sectional ◽

Artrite Reumatoide ◽

Student’S T

AIMS: To evaluate disease activity indexes in female patients with rheumatoid arthritis, Anemic and Non-anemic, correlating with hemoglobin levels.METHODS: A cross-sectional study involved women with rheumatoid arthritis classified into two groups: 1) Anemic (hemoglobin <12 g/dL) and 2) Non-anemic. Disease activity was measured by Disease Activity Index (DAS28), using different inflammatory markers: Erythrocyte Sedimentation Rate (ESR) and C-reative Protein (CRP). This score also uses the number of swollen and painful joints and an overall assessment of the disease on Visual Analogue Scale (VAS). An assessment of functional capacity by the Health Assessment Questionnaire (HAQ) was also performed. The statistic used Student’s t-Test, Mann-Whitney, Wilcoxon, Fisher, likelihood ratio and Spearman correlation tests. It was considered significant p <0,05.RESULTS: Twenty-four patients were included, eight of Anemic group and 16 of Non-anemic. The groups were similar in terms of clinical, demographic and treatment characteristics, differing only in relation to rheumatoid factor, positive in all anemic participants and in 56,2% of non anemic participants. DAS28 ESR (median 6,05; interquartile range [IQR] 5,21-7,76), DAS28 CRP (median 4,32; IQR 3,98-5,92) and VAS (median 66,50 mm; IQR 54,75-80,50) were significantly higher in Anemic group. DAS28 ESR (-0,418) and VAS (-0,426) showed a significant negative correlation with hemoglobin level. DAS28 ESR and DAS28 CRP values were different in the same group, showing a discrepancy in the categorization of disease activity. In Anemic group, DAS28 ESR value (median 6,05; IQR 5,21-7,76) was higher in relation to DAS28 CRP (median 4,32; IQR 3,98-5,92). A less discrepant increase of DAS28 ESR (median 4,01; IQR 3,05-5,68) compared to DAS28 CRP (median 3,06; IQR 2,18-4,66) was observed in Non-anemic group.CONCLUSIONS: Anemia was associated with worse disease activity indexes in women with rheumatoid arthritis, correlated with greater pain intensity and increase of DAS28 ESR score.

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Influence of Ambient Air Pollution on Rheumatoid Arthritis Disease Activity Score Index

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17020416 ◽

2020 ◽

Vol 17 (2) ◽

pp. 416

Author(s):

Ahmad Alsaber ◽

Jiazhu Pan ◽

Adeeba Al-Herz ◽

Dhary Alkandary ◽

Adeeba Al-Hurban ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Air Pollution ◽

Disease Activity ◽

Disease Activity Score ◽

Ambient Air ◽

Activity Score ◽

Unknown Etiology ◽

Das 28 ◽

Increased Risk ◽

Pm 10

Rheumatoid arthritis (RA) is a chronic autoimmune of an unknown etiology. Air pollution has been proposed as one of the possible risk factors associated with disease activity, although has not been extensively studied. In this study, we measured the relationship between exposure to air pollutants and RA activity. Data on RA patients were extracted from the Kuwait Registry for Rheumatic Diseases (KRRD). Disease activity was measured using disease activity score with 28 examined joints (DAS-28) and the Clinical Disease Activity Index (CDAI) during their hospital visits from 2013 to 2017. Air pollution was assessed using air pollution components (PM 10 , NO 2 , SO 2 , O 3 , and CO). Air pollution data were obtained from Kuwait Environmental Public Authority (K-EPA) from six different air quality-monitoring stations during the same period. Multiple imputations by the chained equations (MICE) algorithm were applied to estimate missing air pollution data. Patients data were linked with air pollution data according to date and patient governorate address. Descriptive statistics, correlation analysis, and linear regression techniques were employed using STATA software. In total, 1651 RA patients with 9875 follow-up visits were studied. We detected an increased risk of RA using DAS-28 in participants exposed to SO 2 and NO 2 with β = 0 . 003 (95% CI: 0.0004–0.005, p < 0 . 01 ) and β = 0 . 003 (95% CI: 0.002–0.005, p < 0 . 01 ), respectively, but not to PM 10 , O 3 , and CO concentrations. Conclusively, we observed a strong association between air pollution with RA disease activity. This study suggests air pollution as a risk factor for RA and recommends further measures to be taken by the authorities to control this health problem.

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Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573397115666190122113221 ◽

2019 ◽

Vol 15 (4) ◽

pp. 316-320

Author(s):

Mir Amir Aghdashi ◽

Seyedmostafa Seyedmardani ◽

Sholeh Ghasemi ◽

Zohre Khodamoradi

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Inflammatory Arthritis ◽

Unknown Etiology ◽

Tender Joint Count ◽

Serum Samples ◽

Tender Joint ◽

Cross Sectional ◽

Calprotectin Level ◽

Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

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Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

Lupus ◽

10.1177/0961203319899478 ◽

2020 ◽

Vol 29 (2) ◽

pp. 182-190

Author(s):

W Batista Cicarini ◽

R C Figueiredo Duarte ◽

K Silvestre Ferreira ◽

C de Mello Gomes Loures ◽

R Vargas Consoli ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Endothelial Injury ◽

Control Group ◽

Systemic Lupus ◽

Low Concentrations ◽

The Relationship

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

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AB0655 RHEUMATOID ARTHRITIS ACTIVITY BEFORE AND AFTER COVID-19 LOCKDOWN PERIOD

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.576 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1360.1-1360

Author(s):

M. Jordhani ◽

D. Ruci ◽

F. Skana ◽

E. Memlika

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Musculoskeletal Diseases ◽

Statistical Tests ◽

Laboratory Data ◽

World Population ◽

Chronic Patients ◽

Das 28 ◽

Significant Difference ◽

Before And After

Background:The COVID-19 global pandemic has had a great impact on world population due to morbidity, mortality and restriction measures in order to stop the progression of COVID-19.Patients with rheumatic and musculoskeletic diseases, and especially rheumatoid arthritis (RA) patients, being one of the vulnerable classes of chronic patients, were recommended to follow the government’s rules1.Objectives:The aim of this study was to evaluate DAS-28-ESR in patients with rheumatoid arthritis before and after lockdown period.Methods:This is a multi-center observational study including 85 patients which were evaluated before and after lockdown for their disease activity score according to DAS-28-ESR score. They had been diagnosed with rheumatoid arthritis more than 5 years ago. A thorough physical examination was performed before and after the lockdown period. It included examination of tender and swollen joints and patient’s global health. They were completed with all required laboratory data, including erythrosedimentation rate. For a more accurate calculation, DAS-28-ESR was used in an electronic version. Patients with other inflammatory or infective diseases were excluded from the study. All data were statistically evaluated using statistical tests such as t-student test.Results:The first group (the one before lockdown) had an average DAS-28-ESR of 4.7 while after the lockdown period, the average DAS-28-ESR was 5.16.After statistically evaluating all data, it was found that there exists a significant difference between DAS-28-ESR score before and after COVID-19 lockdown (p=0.0011).Conclusion:Our study showed that lockdown period due to COVID-19 pandemic, has aggravated disease activity in patients with Rheumatoid Arthritis. This may be consequence of various causes such as physical inactivity and difficulty to follow-up or to take the medication properly.References:[1]Landewé RB, Machado PM, Kroon F, et al, EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2, Annals of the Rheumatic Diseases 2020;79:851-858.Disclosure of Interests:None declared.

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The modification effect of temperature on the relationship between air pollutants and daily incidence of influenza in Ningbo, China

Respiratory Research ◽

10.1186/s12931-021-01744-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Rui Zhang ◽

Yujie Meng ◽

Hejia Song ◽

Ran Niu ◽

Yu Wang ◽

...

Keyword(s):

Air Pollution ◽

High Temperature ◽

Air Pollutants ◽

Meteorological Data ◽

Effect Of Temperature ◽

Distributed Lag ◽

Modification Effect ◽

Incidence Risk ◽

The Impact ◽

The Relationship

Abstract Background Although exposure to air pollution has been linked to many health issues, few studies have quantified the modification effect of temperature on the relationship between air pollutants and daily incidence of influenza in Ningbo, China. Methods The data of daily incidence of influenza and the relevant meteorological data and air pollution data in Ningbo from 2014 to 2017 were retrieved. Low, medium and high temperature layers were stratified by the daily mean temperature with 25th and 75th percentiles. The potential modification effect of temperature on the relationship between air pollutants and daily incidence of influenza in Ningbo was investigated through analyzing the effects of air pollutants stratified by temperature stratum using distributed lag non-linear model (DLNM). Stratified analysis by sex and age were also conducted. Results Overall, a 10 μg/m3 increment of O3, PM2.5, PM10 and NO2 could increase the incidence risk of influenza with the cumulative relative risk of 1.028 (95% CI 1.007, 1.050), 1.061 (95% CI 1.004, 1.122), 1.043 (95% CI 1.003, 1.085), and 1.118 (95% CI 1.028, 1.216), respectively. Male and aged 7–17 years were more sensitive to air pollutants. Through the temperature stratification analysis, we found that temperature could modify the impacts of air pollution on daily incidence of influenza with high temperature exacerbating the impact of air pollutants. At high temperature layer, male and the groups aged 0–6 years and 18–64 years were more sensitive to air pollution. Conclusion Temperature modified the relationship between air pollution and daily incidence of influenza and high temperature would exacerbate the effects of air pollutants in Ningbo.

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Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-219876 ◽

2021 ◽

pp. annrheumdis-2021-219876

Author(s):

Evgeniy Nasonov ◽

Saeed Fatenejad ◽

Eugen Feist ◽

Mariana Ivanova ◽

Elena Korneva ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Phase Iii ◽

Double Blind Study ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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POS0009 THE RELATIONSHIP BETWEEN DIFFERENT IGG AND IGA ANTI-MODIFIED PROTEIN AUTOANTIBODIES IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3003 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 206.1-207

Author(s):

C. Grönwall ◽

L. Liljefors ◽

H. Bang ◽

A. Hensvold ◽

M. Hansson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Comprehensive Evaluation ◽

Patient Characteristics ◽

Post Translational Modifications ◽

Cell Clones ◽

Thermo Fisher Scientific ◽

History Of ◽

The Relationship ◽

Fisher Scientific

Background:Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared

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AB0048 ENZYMATIC PATTERN OF CIRCULATING PRO- AND ANTIOXIDANT ENZYMES IN RHEUMATOID ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1754 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1056.2-1057

Author(s):

S. Bedina ◽

E. Mozgovaya ◽

A. Trofimenko ◽

S. Spitsina ◽

M. Mamus

Keyword(s):

Rheumatoid Arthritis ◽

Antioxidant Enzymes ◽

Disease Activity ◽

Neutrophil Extracellular Traps ◽

Unknown Etiology ◽

Antioxidant Enzyme Activities ◽

Reference Ranges ◽

Sod Activity ◽

Low Disease Activity ◽

Extracellular Traps

Background:Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis and systemic organ involvement resulting in early disability and shorter life expectancy. Neutrophils are suggested to play a substantial role in the induction and promotion of autoimmune inflammation in RA. This ability can be based on newly discovered feature of neutrophils to release neutrophil extracellular traps (NETs) during specific type cell death called NETosis. Hyperproduction of reactive oxygen species (ROS) is one of the factors promoting NETs production. With this background, the study of pro- and antioxidant enzymatic activities in RA patients can be of great interest.Objectives:To assess plasma activities of essential prooxidant and antioxidant enzymes in RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 71 RA patients (46 women and 25 men) were enrolled in the study. The diagnosis was verified using ACR/EULAR criteria (2010). RA activity was measured using the Disease Activity Score of 28 joints (DAS28). 30 healthy persons comprise control group. Plasma xanthine oxidase (XO; ЕС 1.17.3.2), xanthine dehydrogenase (XDH; ЕС 1.17.1.4) and superoxide dismutase (SOD; ЕС 1.15.1.1) activities were measured using spectrophotometric technique. XO and XDG activities were expressed as nmol/ml/min, SOD activity – as units of action. Statistical analysis was performed using Statistica 6.0 software package. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:Mean age of patients was 43.2±3.6 years, mean RA duration was 11.9±2.6 years. 24 (33.8%) RA patients had low disease activity, and 6 (8.5%) patients had high one. Extra-articular manifestations were found in 30 (42.2%) patients. 30% of them had cardiovascular involvement, 23.3% – pulmonary lesions, and 23.3% had renal involvement. Reference ranges for XO, XDG, and SOD activities were 2.28-5.12 nmol/min/ml, 3,96-7,24 nmol/min/ml, and 3,13-6,58 units, respectively. We examined activities of these enzymes in circulation of RA patients with different patterns of clinical manifestations as well as relationship between RA activity and XO, XDG, and SOD activities. RA patients had increased both mean XO and mean SOD activities (p<0.001 for both enzymes). XO activity reached its highest values at maximum disease activity and overt extra-articular involvements, while SOD activity did it in moderate and high disease activities as well as in patients with joint manifestations. XDG activity was increased in low disease activity (р<0.001) and solely joint lesions (р=0.011), while moderate or high disease activities (р=0.008) and extra-articular involvements (р=0.025) were characterized by decreased activity of this enzyme.Conclusion:We have revealed substantial multidirectional changes of plasma XO and XDG activities in RA. Plasma enzymatic pattern in RA patients is characterized by activation of both oxidant and antioxidant metabolic pathways. Activities of XO and SOD were positively correlated with RA activity, while XDG activity was negative correlated with RA activity. The differences between selective articular RA type and RA form with extraarticular manifestations were also revealed. Changes in oxidant and antioxidant enzyme activities can be connected with anticitrulline autoimmunity in RA via production of citrulline-rich neutrophil extracellular traps, thus enhancing rheumatoid autoimmunity.Disclosure of Interests:None declared

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