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      Antieosinophil Antibodies Alone or in Combination with Antineutrophil Cytoplasmic Antibodies (ANCA) Detected in Different Autoimmune Conditions


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          Circulating antieosinophil antibodies (AEOSA) have been associated with various autoimmune conditions affecting the liver, kidneys, lungs, and joints but are not part of routine clinical diagnostics. While analyzing human sera for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) on granulocytes, 0.8% of analyzed samples were found to be reactive with eosinophils. Our aim was to determine the diagnostic relevance and antigenic specificity of AEOSA. AEOSA were seen either in combination with an myeloperoxidase (MPO)-positive p-ANCA (44%; AEOSA+/ANCA+) or on their own (56%; AEOSA+/ANCA−). AEOSA/ANCA positivity was seen in patients with thyroid disease (44%) or vasculitis (31%), while AEOSA+/ANCA− pattern was more common in patients with autoimmune disorders of the gastrointestinal tract and/or liver. Eosinophil peroxidase (EPX) was the main target recognized in 66% of the AEOSA+ sera by enzyme-linked immunosorbent assay (ELISA). Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were also identified as target antigens but less frequently and only in combination with EPX. In conclusion, we confirmed that EPX is a major target of AEOSA, illustrating the high antigenic potential of EPX. Our results also demonstrate the presence of concomitant AEOSA/ANCA positivity in a defined patient group. Further research should aim to elucidate the association of AEOSA with autoimmunity.

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          Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis.

          Uveitis, psoriasis and inflammatory bowel disease (IBD) are common extra-articular manifestations (EAM) in patients with ankylosing spondylitis (AS); however, summary data of reported prevalence are lacking. The aim of the present study was to summarise the prevalence of EAMs among patients with AS and to identify underlying factors to explain potential heterogeneity of prevalence. A systematic literature search was performed (Medline, Embase and Cochrane Library) to identify relevant articles. Risk of bias was assessed and data were extracted. Pooled prevalences were calculated. Potential sources of any observed clinical or methodological heterogeneity in the estimates were explored by subgroup and metaregression analysis. In the 156 selected articles, 143 reported the prevalence of uveitis (44 372 patients), 56 of psoriasis (27 626 patients) and 69 of IBD (30 410 patients). Substantial heterogeneity was observed in prevalence estimates among all EAMs (I(2)=84-95%). The pooled prevalence of uveitis was 25.8% (95% CI 24.1% to 27.6%), and was positively associated in multivariable metaregression with disease duration (β 0.05, 95% CI 0.03 to 0.08) and random selection of patients (β -0.24, 95% CI -0.43 to -0.04). The pooled prevalence of psoriasis was 9.3% (95% CI 8.1% to 10.6%). The pooled prevalence of IBD was 6.8% (95% CI 6.1% to 7.7%) and was positively associated with the percentage of women in the studies (β 0.02, 95% CI 0.00 to 0.03). Geographical area was associated in multivariable metaregressions with prevalence of all EAMs. EAMs are common in patients with AS. The large heterogeneity between studies can be partly explained by differences in clinical as well as methodological characteristics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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            Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species.

            Neutrophil extracellular traps (NETs) are mesh-like DNA fibers clad with intracellular proteins that are cast out from neutrophils in response to certain stimuli. The process is thought to depend on reactive oxygen species (ROS) generated by the phagocyte NADPH-oxidase and the ROS-modulating granule enzyme myeloperoxidase (MPO), but when, how, and where these factors contribute is so far uncertain. The neutrophil NADPH-oxidase can be activated at different cellular sites and ROS may be produced and processed by MPO within intracellular granules, even in situations where a phagosome is not formed, e.g., upon stimulation with phorbol myristate acetate (PMA).
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              Sputum autoantibodies in patients with severe eosinophilic asthma.

              The persistence of eosinophils in sputum despite high doses of corticosteroids indicates disease severity in asthmatic patients. Chronic inflamed airways can lose tolerance over time to immunogenic entities released on frequent eosinophil degranulation, which further contributes to disease severity and necessitates an increase in maintenance corticosteroids.

                Author and article information

                J Immunol Res
                J Immunol Res
                Journal of Immunology Research
                26 April 2023
                : 2023
                : 5980287
                1Department of Rheumatology and Inflammation Research, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                2Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
                3Department of Oral Microbiology and Immunology, Institute of Odontology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                4Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
                5Department of Molecular and Clinical Medicine, Institute of Biomedicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                6Institute of Biomedicine, Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                7Department of Clinical Microbiolog, Sahlgrenska University Hospital, Gothenburg, Sweden
                Author notes

                Academic Editor: Lalit Batra

                Author information
                Copyright © 2023 Régis Dieckmann et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 29 December 2022
                : 17 March 2023
                : 18 March 2023
                Funded by: Sahlgrenska University Hospitals Research Foundations
                Funded by: Reumatikerförbundet
                Award ID: R-663511
                Funded by: Göteborgs Universitet
                Award ID: ALF/GBG-926621
                Award ID: ALF/GBG-966039
                Funded by: Vetenskapsrådet
                Award ID: 2019-01123
                Funded by: Hjärt-Lungfonden
                Award ID: 2021-2407
                Funded by: King Gustaf V Memorial Foundation
                Award ID: FAI-2021-0768
                Funded by: Insamlingsstiftelsen Cancer- och Allergifonden
                Award ID: 2020-10154
                Research Article


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