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      Clinical significance of BPI‐ANCA detecting in COPD patients with Pseudomonas aeruginosa colonization

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          Abstract

          Background

          Antineutrophil cytoplasmic autoantibodies against neutrophil granule bactericidal/permeability‐increasing protein (BPI‐ANCA) has been found in many inflammatory diseases, such as COPD, which can reduce the killing effect of BPI on Gram‐negative bacteria. This study was aimed to assess the clinical significance of BPI‐ANCA detecting in COPD patients with Pseudomonas aeruginosa ( P aeruginosa) colonization.

          Methods

          A total of 216 COPD patients with lung P aeruginosa colonization, 244 patients with P aeruginosa infection from June 2015 to June 2018, and 100 healthy individuals were included. Serum BPI‐ANCA, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐6 and IL‐1β levels were detected by ELISA, and the lung function of the patients was measured at stable clinical stages. Patients with COPD were grouped according to BPI‐ANCA detection and GOLD criteria, and serum TNF‐α, IL‐6, and IL‐1β levels and indices reflecting lung function were compared and analyzed between groups.

          Results

          Positive rate of BPI‐ANCA in COPD patients with P aeruginosa colonization was 48.15%; and compared with BPI‐ANCA(‐) group, FEV 1%pred and FEV 1/FVC(%) in BPI‐ANCA(+) patients were significantly decreased, while TNF‐α, IL‐6, and IL‐1β levels were elevated. There were 31.73% and 36.54% BPI‐ANCA(+) patients with severe and very severe airflow limitation, respectively, which was significantly higher than that in the BPI‐ANCA(‐) group. FEV 1%pred and FEV 1/FVC(%) were negatively correlated with TNF‐α, IL‐6, IL‐1β, and NEU%. C‐reactive protein (CRP) was negatively correlated with FEV 1%pred, yet not significantly correlated with FEV 1/FVC(%).

          Conclusion

          BPI‐ANCA positivity is associated with inflammatory status in COPD patients with pulmonary P aeruginosa colonization and can be used as a potential biomarker assessing disease severity.

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          Most cited references14

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          Infections and antineutrophil cytoplasmic antibodies: triggering mechanisms.

          The precise cause of the antineutrophil cytoplasmic antibodies (ANCA) autoimmunity is not known and is likely to be multifactorial. Infections may trigger formation of ANCA and a fraction of the patients with infection-triggered ANCA develop ANCA-associated vasculitis. Here we discuss some of the proposed mechanisms of ANCA formation during the course of infection. They include initiation of autoimmune response by microbial peptides that are complementary to autoantigens; epigenetic silencing and antigen complementarity leading to upregulation of autoantigen genes; molecular mimicry between bacterial and self-antigens; formation of neutrophil extracellular traps that stimulate immune processes including production of ANCA; and interaction of bacterial components with Toll-like receptors, which leads to formation of mediators affecting the immune responses to infections and can trigger ANCA production. Further work is needed to clarify these mechanisms and develop preventive measures and therapeutic interventions.
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            The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease.

            Gram-negative bacteria (GNB) and their endotoxin present a constant environmental challenge. Endotoxins can potently signal mobilization of host defenses against invading GNB but also potentially induce severe pathophysiology, necessitating controlled initiation and resolution of endotoxin-induced inflammation to maintain host integrity. The bactericidal/permeability-increasing protein (BPI) is a pluripotent protein expressed, in humans, mainly neutrophils. BPI exhibits strong antimicrobial activity against GNB and potent endotoxin-neutralizing activity. BPI mobilized with neutrophils in response to invading GNB can promote intracellular and extracellular bacterial killing, endotoxin neutralization and clearance, and delivery of GNB outer membrane antigens to dendritic cells. Tissue expression by dermal fibroblasts and epithelia could further amplify local levels of BPI and local interaction with GNB and endotoxin, helping to constrain local tissue infection and inflammation and prevent systemic infection and systemic inflammation. This review article focuses on the structural and functional properties of BPI with respect to its contribution to host defense during GNB infections and endotoxin-induced inflammation and the genesis of autoantibodies against BPI that can blunt BPI activity and potentially contribute to chronic inflammatory disease.
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              Chronic obstructive pulmonary disease (COPD): evaluation from clinical, immunological and bacterial pathogenesis perspectives.

              Chronic obstructive pulmonary disease (COPD), a disease manifested by significantly impaired airflow, afflicts ∼14.2 million cases in the United States alone with an estimated 63 million people world-wide. Although there are a number of causes, the predominant cause is excessive tobacco smoke. In fact, in China, there have been estimates of 315,000,000 people that smoke. Other less frequent causes are associated with indirect cigarette smoke, air pollutants, biomass fuels, and genetic mutations. COPD is often associated with heart disease, lung cancer, osteoporosis and conditions can worsen in patients with sudden falls. COPD also affects both innate and adaptive immune processes. Cigarette smoke increases the expression of matrix metalloproteases and proinflammatory chemokines and increases lung titers of natural killer cells and neutrophils. Yet, neutrophil reactive oxygen species (ROS) mediated by the phagocytic respiratory burst and phagocytosis is impaired by nicotine. In contrast to innate immunity in COPD, dendritic cells represent leukocytes recruited to the lung that link the innate immune responses to adaptive immune responses by activating naïve T cells through antigen presentation. The autoimmune process that is also a significant part of inflammation associated with COPD. Moreover, coupled with restricted FEV1 values, are the prevalence of patients with single or multiple infections by bacteria, viruses and fungi. Finally, we focus on one of the more problematic infectious agents, the Gram-negative opportunistic pathogenic bacterium, Pseudomonas aeruginosa. Specifically, we delve into the development of highly problematic biofilm infections that are highly refractory to conventional antibiotic therapies in COPD. We offer a non-conventional, biocidal treatment that may be effective for COPD airway infections as well as with combinations of current antibiotic regimens for more effective treatment outcomes and relief for patients with COPD.
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                Author and article information

                Contributors
                ndefy84029@ncu.edu.cn
                Journal
                J Clin Lab Anal
                J. Clin. Lab. Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                20 May 2019
                July 2019
                : 33
                : 6 ( doiID: 10.1002/jcla.2019.33.issue-6 )
                : e22908
                Affiliations
                [ 1 ] Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine the Second Affiliated Hospital of Nanchang University Nanchang China
                Author notes
                [*] [* ] Correspondence

                Liming Tan, Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, the NO.1 Minde Road, Donghu District, Nanchang, Jiangxi, China.

                Email: ndefy84029@ 123456ncu.edu.cn

                Author information
                https://orcid.org/0000-0002-4943-9116
                https://orcid.org/0000-0001-9938-1656
                Article
                JCLA22908
                10.1002/jcla.22908
                6642326
                31106488
                9621e104-bab3-4ee1-a229-ebf3f58899d6
                © 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 October 2018
                : 21 March 2019
                : 15 April 2019
                Page count
                Figures: 1, Tables: 5, Pages: 7, Words: 4395
                Funding
                Funded by: National Nature Science Foundation of China
                Award ID: 81760382
                Funded by: Grants from Jiangxi Provincial Science and Technology Bureau
                Award ID: 20151122070198
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                jcla22908
                July 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.0 mode:remove_FC converted:24.10.2019

                Clinical chemistry
                antineutrophil cytoplasm autoantibodies,bactericidal/permeability‐increasing protein,chronic obstructive pulmonary disease,cytokines,pseudomonas aeruginosa

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