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      Association between TNFi anti-drug antibodies, smoking, and disease activity in patients with inflammatory arthritis: Results from a Norwegian cross-sectional observational study

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          Abstract

          Introduction

          We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive.

          Methods

          TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models.

          Results

          A total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient’s global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb ( p < 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients ( p < 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes ( p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses ( p ≤ 0.008).

          Conclusions

          nADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40744-022-00464-7.

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          Most cited references15

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          Rheumatoid arthritis.

          Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis.
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            Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

            Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells. Complex roles of cigarette smoke have resulted in numerous diseases, including cardiovascular, respiratory and autoimmune diseases, allergies, cancers and transplant rejection etc. Although previous reviews have described the effects of smoking on various diseases and regional immunity associated with specific diseases, a comprehensive and updated review is rarely seen to demonstrate impacts of smoking on general immunity and, especially on major components of immune cells. Here, we aim to systematically and objectively review the influence of smoking on major components of both innate and adaptive immune cells, and summarize cellular and molecular mechanisms underlying effects of cigarette smoking on the immune system. The molecular pathways impacted by cigarette smoking involve NFκB, MAP kinases and histone modification. Further investigations are warranted to understand the exact mechanisms responsible for smoking-mediated immunopathology and to answer lingering questions over why cigarette smoking is always harmful rather than beneficial even though it exerts dual effects on immune responses.
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              Effects of tobacco smoke on immunity, inflammation and autoimmunity.

              Smoking is a central factor in many pathological conditions. Its role in neoplasm, lung and cardiovascular diseases has been well established for years. However it is less acknowledged the cigarette smoking affects both the innate and adoptive immune arms. Cigarette smoke was shown to augment the production of numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8 GM-CSF and to decrease the levels of anti-inflammatory cytokines such as IL-10. Tobacco smoke via multiple mechanisms leads to elevated IgE concentrations and to the subsequent development of atopic diseases and asthma. Cigarette smoke has also been shown activate in many ways macrophage and dendritic cell activity. While it is better evident how cigarette smoke evokes airway diseases more mechanisms are being revealed linking this social hazard to autoimmune disorders, for instance via the production of antibodies recognizing citrullinated proteins in rheumatoid arthritis or by the elevation of anti-dsDNA titers in systemic lupus erythematosus. The current review underlines the importance of smoking prevention and eradication not only in respiratory disorders but also in autoimmune conditions as well. Copyright 2009 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                brigitte_michelsen@yahoo.no
                Journal
                Rheumatol Ther
                Rheumatol Ther
                Rheumatology and Therapy
                Springer Healthcare (Cheshire )
                2198-6576
                2198-6584
                20 May 2022
                20 May 2022
                August 2022
                : 9
                : 4
                : 1171-1179
                Affiliations
                [1 ]GRID grid.417290.9, ISNI 0000 0004 0627 3712, Division of Rheumatology, Department of Medicine, , Sørlandet Hospital, ; Service Box 416, 4604 Kristiansand, Norway
                [2 ]GRID grid.417290.9, ISNI 0000 0004 0627 3712, Department of Clinical Immunology and Transfusion Medicine, , Sørlandet Hospital, ; Kristiansand, Norway
                [3 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Division of Rheumatology, Allergy, Immunology, , University of California San Diego, ; San Diego, CA USA
                [4 ]GRID grid.5947.f, ISNI 0000 0001 1516 2393, Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, , NTNU, Norwegian University of Science and Technology, ; Trondheim, Norway
                Author information
                http://orcid.org/0000-0003-0103-2840
                http://orcid.org/0000-0001-6942-5830
                http://orcid.org/0000-0002-9279-5191
                Article
                464
                10.1007/s40744-022-00464-7
                9314485
                35594016
                23d3f113-1178-4e12-828d-74ea28e1eb74
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 22 March 2022
                : 7 May 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100012266, Norsk Revmatikerforbund;
                Funded by: FundRef http://dx.doi.org/10.13039/100004319, Pfizer;
                Funded by: Calpro AS
                Categories
                Brief Report
                Custom metadata
                © The Author(s) 2022

                rheumatoid arthritis,psoriatic arthritis,ankylosing spondylitis,tumor necrosis factor inhibitors

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