{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:05:00Z","timestamp":1791302700360,"version":"4.1.0"},"reference-count":47,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"ThermoFisher Diagnostics"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2022,12,23]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in the prediction of clinical features and outcome. The study of RF isotypes has further attempted to improve diagnostic accuracy and identify specific subgroups of patients. The main objective of this study is to provide an analysis of the literature on the role of RF isotypes in the diagnosis and prognosis of rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a systematic literature review and meta-analysis on the role of RF isotypes in RA (only in English, from PubMed, search terms: \u201crheumatoid factor isotypes\u201d, \u201cdiagnosis\u201d, \u201cprognosis\u201d and \u201crheumatoid arthritis\u201d, last search 31 July 2022, two independent assessment of quality and biases, results included in tables and in the meta-analysis).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-six articles were examined (7517 patients). Testing all RF isotypes with latex test or nephelometry allows for the highest sensitivity (68.6%, 95% CI 66.2% to 71.0%); nonetheless, the determination of IgA isotype provides the highest specificity (91.4%, 95% CI 90.8% to 92.0%) and the highest positive likelihood ratio (7.7, 95% CI 5.7 to 10.4). When testing IgM isotype the highest diagnostic OR (21.7, 95% CI 16.1 to 29.3) is reached. When analysing anti-citrullinated protein antibodies, RF isotype determination increases diagnostic accuracy. On the other hand, these do not provide relevant prognostic information, as results are conflicting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Testing RF allows the highest sensitivity, while IgA isotype the highest specificity and positive likelihood ratio for RA diagnosis. On the other hand, determination of RF isotypes dose not allow prognostic information, as data are limited and heterogeneous.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002817","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:31:01Z","timestamp":1691152261000},"page":"e002817","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["Rheumatoid factor isotypes in rheumatoid arthritis diagnosis and prognosis: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8093-2734","authenticated-orcid":false,"given":"Francesca","family":"Motta","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-6983","authenticated-orcid":false,"given":"Nicola","family":"Bizzaro","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology, Azienda Sanitaria Universitaria Integrata, Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Giavarina","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, St Bortolo Hospital, Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"},{"name":"Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-4467","authenticated-orcid":false,"given":"Maria","family":"Infantino","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Allergology, Ospedale San Giovanni di Dio, Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boaz","family":"Palterer","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Domenico","family":"Sebastiani","sequence":"additional","affiliation":[{"name":"Rheumatology, Azienda Ospedaliera San Camillo Forlanini, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-0376","authenticated-orcid":false,"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology 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