{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:24:27Z","timestamp":1794014667439,"version":"4.8.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006722","name":"Centrum f\u00d6r Klinisk Forskning Dalarna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010805","name":"Forskningsr\u00e5det i Syd\u00f6stra Sverige","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010805","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Reinhold Sund foundation"},{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u00d6sterg\u00f6tland County Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Circulating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RA patients (<jats:italic>n<\/jats:italic>\u2009=\u2009196) and healthy blood donors (<jats:italic>n<\/jats:italic>\u2009=\u2009101), included in the cross-sectional study \u201cSecretory ACPA in Rheumatoid Arthritis\u201d (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1\/shared epitope (SE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (<jats:italic>r<\/jats:italic>\u2009=\u20090.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Salivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13075-020-02363-0","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T12:03:46Z","timestamp":1606133026000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis"],"prefix":"10.1186","volume":"22","author":[{"given":"Karin","family":"Roos Ljungberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"B\u00f6rjesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Martinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Wetter\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alf","family":"Kastbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sv\u00e4rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"issue":"1","key":"2363_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/BOR.0000000000000017","volume":"26","author":"MK Demoruelle","year":"2014","unstructured":"Demoruelle MK, Deane KD, Holers VM. When and where does inflammation begin in rheumatoid arthritis? Curr Opin Rheumatol. 2014;26(1) (1531\u20136963 (Electronic)):64\u201371.","journal-title":"Curr Opin Rheumatol"},{"issue":"9","key":"2363_CR2","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41584-018-0070-0","volume":"14","author":"VM Holers","year":"2018","unstructured":"Holers VM, Demoruelle MK, Kuhn KA, Buckner JH, Robinson WH, Okamoto Y, et al. Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nat Rev Rheumatol. 2018;14(9):542\u201357.","journal-title":"Nat Rev Rheumatol"},{"issue":"10","key":"2363_CR3","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1002\/art.11223","volume":"48","author":"S Rantapaa-Dahlqvist","year":"2003","unstructured":"Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48(10):2741\u20139.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2363_CR4","doi-asserted-by":"publisher","first-page":"R13","DOI":"10.1186\/ar3237","volume":"13","author":"H Kokkonen","year":"2011","unstructured":"Kokkonen H, Mullazehi M, Berglin E, Hallmans G, Wadell G, Ronnelid J, et al. Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res Ther. 2011;13(1):R13.","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"2363_CR5","doi-asserted-by":"publisher","first-page":"R75","DOI":"10.1186\/ar2449","volume":"10","author":"A Svard","year":"2008","unstructured":"Svard A, Kastbom A, Reckner-Olsson A, Skogh T. Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis: the Swedish TIRA project. Arthritis Res Ther. 2008;10(4):R75.","journal-title":"Arthritis Res Ther."},{"issue":"2","key":"2363_CR6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.imbio.2012.04.011","volume":"218","author":"A Svard","year":"2013","unstructured":"Svard A, Kastbom A, Sommarin Y, Skogh T. Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis. Immunobiology. 2013;218(2):232\u20137.","journal-title":"Immunobiology."},{"issue":"6","key":"2363_CR7","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/mi.2011.36","volume":"4","author":"JE Bakema","year":"2011","unstructured":"Bakema JE, van Egmond M. The human immunoglobulin A Fc receptor FcalphaRI: a multifaceted regulator of mucosal immunity. Mucosal Immunol. 2011;4(6):612\u201324.","journal-title":"Mucosal Immunol"},{"key":"2363_CR8","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3389\/fimmu.2013.00222","volume":"4","author":"P Brandtzaeg","year":"2013","unstructured":"Brandtzaeg P. Secretory IgA: designed for anti-microbial defense. Front Immunol. 2013;4:222.","journal-title":"Front Immunol"},{"key":"2363_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.3389\/fimmu.2019.00553","volume":"10","author":"A Breedveld","year":"2019","unstructured":"Breedveld A, van Egmond M. IgA and FcalphaRI: pathological roles and therapeutic opportunities. Front Immunol. 2019;10:553.","journal-title":"Front Immunol"},{"issue":"6","key":"2363_CR10","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/mi.2011.39","volume":"4","author":"JM Woof","year":"2011","unstructured":"Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal Immunol. 2011;4(6):590\u20137.","journal-title":"Mucosal Immunol"},{"issue":"3","key":"2363_CR11","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1128\/CVI.00475-09","volume":"17","author":"SH Pakkanen","year":"2010","unstructured":"Pakkanen SH, Kantele JM, Moldoveanu Z, Hedges S, Hakkinen M, Mestecky J, et al. Expression of homing receptors on IgA1 and IgA2 plasmablasts in blood reflects differential distribution of IgA1 and IgA2 in various body fluids. Clin Vaccine Immunol. 2010;17(3):393\u2013401.","journal-title":"Clin Vaccine Immunol"},{"key":"2363_CR12","first-page":"383","volume":"47","author":"D Delacroix","year":"1982","unstructured":"Delacroix D, Dive C, Rambaud JC, Vaerman JP. IgA subclasses in various secretions and in serum. Immunology. 1982;47(0019\u20132805 (Print)):383\u20135.","journal-title":"Immunology"},{"key":"2363_CR13","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1134\/S0006297907050045","volume":"72","author":"TN Kazeeva","year":"2007","unstructured":"Kazeeva TN, Shevelev AB. Unknown functions of immunoglobulins A. Biochemistry (Mosc). 2007;72(0006\u20132979 (Print)):485\u201394.","journal-title":"Biochemistry (Mosc)"},{"issue":"1","key":"2363_CR14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4049\/jimmunol.105.1.43","volume":"105","author":"RH Waldman","year":"1970","unstructured":"Waldman RH, Mach JP, Stella MM, Rowe DS. Secretory IgA in human serum. J Immunol. 1970;105(1):43\u20137.","journal-title":"J Immunol"},{"issue":"1","key":"2363_CR15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/art.38201","volume":"66","author":"G Reynisdottir","year":"2014","unstructured":"Reynisdottir G, Karimi R, Joshua V, Olsen H, Hensvold AH, Harju A, et al. Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis. Artritis Rheumatol. 2014;66(1):31\u20139.","journal-title":"Artritis Rheumatol"},{"issue":"10","key":"2363_CR16","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1002\/art.38066","volume":"65","author":"VC Willis","year":"2013","unstructured":"Willis VC, Demoruelle MK, Derber LA, Chartier-Logan CJ, Parish MC, Pedraza IF, et al. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 2013;65(10):2545\u201354.","journal-title":"Arthritis Rheum"},{"issue":"4","key":"2363_CR17","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1093\/rheumatology\/kez377","volume":"59","author":"K Roos Ljungberg","year":"2020","unstructured":"Roos Ljungberg K, Joshua V, Skogh T, Eklund A, Sk\u00f6ld CM, Karimi R, et al. Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis. Rheumatology (Oxford). 2020;59(4):852\u20139.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"2363_CR18","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13075-016-1014-1","volume":"18","author":"K Roos","year":"2016","unstructured":"Roos K, Martinsson K, Ziegelasch M, Sommarin Y, Svard A, Skogh T, et al. Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking. Arthritis Res Ther. 2016;18(1):119.","journal-title":"Arthritis Res Ther."},{"key":"2363_CR19","first-page":"253","volume":"2","author":"G Lakos","year":"2008","unstructured":"Lakos G, Soos L, Fekete A, Szabo Z, Zeher M, Horvath IF, et al. Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope. Clin Exp Rheumatol. 2008;2(0392-856X (Print)):253\u201360.","journal-title":"Clin Exp Rheumatol"},{"key":"2363_CR20","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1002\/art.39170","volume":"67","author":"A Svard","year":"2015","unstructured":"Svard A, Skogh T, Alfredsson L, Ilar A, Klareskog L, Bengtsson C, et al. Associations with smoking and shared epitope differ between IgA- and IgG-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis. Artritis Rheumatol. 2015;67(2326\u20135205 (Electronic)):2032\u20137.","journal-title":"Artritis Rheumatol"},{"issue":"6","key":"2363_CR21","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3899\/jrheum.091323","volume":"37","author":"CA Hitchon","year":"2010","unstructured":"Hitchon CA, Chandad F, Ferucci ED, Willemze A, Ioan-Facsinay A, van der Woude D, et al. Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. J Rheumatol. 2010;37(6):1105\u201312.","journal-title":"J Rheumatol"},{"issue":"5","key":"2363_CR22","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1136\/annrheumdis-2018-213697","volume":"78","author":"G Courbon","year":"2019","unstructured":"Courbon G, Rinaudo-Gaujous M, Blasco-Baque V, Auger I, Caire R, Mijola L, et al. Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat. Ann Rheum Dis. 2019;78(5):594\u20139.","journal-title":"Ann Rheum Dis"},{"issue":"7","key":"2363_CR23","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/art.1780340708","volume":"34","author":"HG Otten","year":"1991","unstructured":"Otten HG, Daha MR, van Laar JM, de Rooy HH, Breedveld FC. Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites. Arthritis Rheum. 1991;34(7):831\u20139.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"2363_CR24","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/art.21575","volume":"54","author":"L Klareskog","year":"2006","unstructured":"Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006;54(1):38\u201346.","journal-title":"Arthritis Rheum"},{"issue":"4","key":"2363_CR25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3109\/03009748809098795","volume":"17","author":"C Ekdahl","year":"1988","unstructured":"Ekdahl C, Eberhardt K, Andersson SI, Svensson B. Assessing disability in patients with rheumatoid arthritis. Use of a Swedish version of the Stanford Health Assessment Questionnaire. Scand J Rheumatol. 1988;17(4):263\u201371.","journal-title":"Scand J Rheumatol"},{"key":"2363_CR26","doi-asserted-by":"crossref","unstructured":"Prevoo ML, Van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38(1):44\u201348.","DOI":"10.1002\/art.1780380107"},{"issue":"9","key":"2363_CR27","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1136\/ard.2003.016808","volume":"63","author":"A Kastbom","year":"2004","unstructured":"Kastbom A, Strandberg G, Lindroos A, Skogh T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004;63(9):1085\u20139.","journal-title":"Ann Rheum Dis"},{"key":"2363_CR28","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.4049\/jimmunol.136.10.3631","volume":"136","author":"K Kett","year":"1986","unstructured":"Kett K, Brandtzaeg P, Radl J, Haaijman JJ. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986;136(0022\u20131767 (Print)):3631\u20135.","journal-title":"J Immunol"},{"issue":"1","key":"2363_CR29","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41467-019-13992-8","volume":"11","author":"U Steffen","year":"2020","unstructured":"Steffen U, Koeleman CA, Sokolova MV, Bang H, Kleyer A, Rech J, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun. 2020;11(1):120.","journal-title":"Nat Commun"},{"issue":"1","key":"2363_CR30","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1136\/annrheumdis-2018-213724","volume":"78","author":"MAM van Delft","year":"2019","unstructured":"van Delft MAM, van der Woude D, Toes REM, Trouw LA. Secretory form of rheumatoid arthritis-associated autoantibodies in serum are mainly of the IgM isotype, suggesting a continuous reactivation of autoantibody responses at mucosal surfaces. Ann Rheum Dis. 2019;78(1):146\u20138.","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"2363_CR31","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1093\/rheumatology\/kez348","volume":"59","author":"K Martinsson","year":"2020","unstructured":"Martinsson K, Roos Ljungberg K, Ziegelasch M, Cedergren J, Eriksson P, Klimovich V, et al. Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk. Rheumatology (Oxford). 2020;59(5):979\u201387.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"2363_CR32","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12967-018-1588-2","volume":"16","author":"M Engstrom","year":"2018","unstructured":"Engstrom M, Eriksson K, Lee L, Hermansson M, Johansson A, Nicholas AP, et al. Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis. J Transl Med. 2018;16(1):214.","journal-title":"J Transl Med"},{"issue":"2","key":"2363_CR33","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/jre.12002","volume":"48","author":"GP Harvey","year":"2013","unstructured":"Harvey GP, Fitzsimmons TR, Dhamarpatni AASSK, Marchant C, Haynes DR, Bartold PM. Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva. J Periodontal Res. 2013;48(2):252\u201361.","journal-title":"J Periodontal Res"},{"issue":"7","key":"2363_CR34","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1600-051X.2012.01885.x","volume":"39","author":"W Nesse","year":"2012","unstructured":"Nesse W, Westra J, van der Wal JE, Abbas F, Nicholas AP, Vissink A, et al. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J Clin Periodontol. 2012;39(7):599\u2013607.","journal-title":"J Clin Periodontol"},{"issue":"12","key":"2363_CR35","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.3899\/jrheum.180897","volume":"46","author":"HM Berens","year":"2019","unstructured":"Berens HM, Polinski KJ, Mikuls TR, Khatter S, August J, Visser A, et al. Anticyclic citrullinated peptide antibodies 3.1 and anti-CCP-IgA are associated with increasing age in individuals without rheumatoid arthritis. J Rheumatol. 2019;46(12):1556\u20139.","journal-title":"J Rheumatol"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02363-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-020-02363-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02363-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:52:33Z","timestamp":1697194353000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-02363-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2363"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-02363-0","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]},"assertion":[{"value":"25 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Open Access funding statement has been added.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the ethical review board in Uppsala, Sweden, and all participants signed a written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"274"}}