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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">rsp</journal-id><journal-title-group><journal-title xml:lang="ru">Научно-практическая ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Rheumatology Science and Practice</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1995-4484</issn><issn pub-type="epub">1995-4492</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47360/1995-4484-2023-207-213</article-id><article-id custom-type="elpub" pub-id-type="custom">rsp-3323</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL RESEARCH</subject></subj-group></article-categories><title-group><article-title>Клинические особенности АЦЦП-негативного и АЦЦП-позитивного вариантов ревматоидного артрита</article-title><trans-title-group xml:lang="en"><trans-title>Clinical features of ACPA-negative and ACPA-positive variants of rheumatoid arthritis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3183-0464</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дибров</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Dibrov</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><email xlink:type="simple">dibrovd995@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3057-9175</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Авдеева</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Avdeeva</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1404-4963</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рыбакова</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Rybakova</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3065-4235</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Демидова</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Demidova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1598-8360</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Насонов</surname><given-names>Е. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Nasonov</surname><given-names>E. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а; 119991, Москва, ул. Трубецкая, 8, стр. 2</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A;</p><p>119991, Moscow, Trubetskaya str., 8, building 2</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»<country>Россия</country></aff><aff xml:lang="en">V.A. Nasonova Research Institute of Rheumatology<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский Университет)<country>Россия</country></aff><aff xml:lang="en">V.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>28</day><month>04</month><year>2023</year></pub-date><volume>61</volume><issue>2</issue><fpage>207</fpage><lpage>213</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Дибров Д.А., Авдеева А.С., Рыбакова В.В., Демидова Н.В., Насонов Е.Л., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Дибров Д.А., Авдеева А.С., Рыбакова В.В., Демидова Н.В., Насонов Е.Л.</copyright-holder><copyright-holder xml:lang="en">Dibrov D.A., Avdeeva A.S., Rybakova V.V., Demidova N.V., Nasonov E.L.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://rsp.mediar-press.net/rsp/article/view/3323">https://rsp.mediar-press.net/rsp/article/view/3323</self-uri><abstract><p>Цель исследования – изучить особенности клинической картины заболевания у пациентов с негативным и позитивным по антителам к циклическому цитруллинированному пептиду (АЦЦП) вариантами ревматоидного артрита (РА).</p><sec><title>Материалы и методы</title><p>Материалы и методы. В исследование были включены больные с достоверным диагнозом РА, соответствующие критериям Американской коллегии ревматологов/Европейского альянса ревматологических ассоциаций (ACR/EULAR, American College of Rheumatology/European Alliance of Associations for Rheumatology) 2010 г. Выделены две группы пациентов: АЦЦП-позитивная (АЦЦП(+)) и АЦЦП-негативная (АЦЦП(–)), которые были сопоставимы по полу, возрасту, длительности заболевания и проводимой терапии. Оценивались характер дебюта и течения заболевания, активность РА (по индексам DAS28 (Disease Activity Score), SDAI (Simplified Disease Activity Score), CDAI (Clinical Disease Activity Score)).</p></sec><sec><title>Результаты</title><p>Результаты. Включены 79 пациентов с АЦЦП(+) и 79 пациентов с АЦЦП(–) РА. Медиана возраста АЦЦП(–) больных составила 52 [39; 62] года, АЦЦП(+) больных – 54 [42; 62] года; длительность заболевания – 59 [23; 122] и 48 [17; 84] месяцев соответственно. У АЦЦП(+) пациентов определялись более высокая активность заболевания по индексам DAS28-СРБ (DAS28 с определением уровня C-реактивного белка), DAS28-СОЭ (DAS28 с определением скорости оседания эритроцитов), SDAI, CDAI, более высокие значения CРБ и СОЭ, большее число болезненных и припухших суставов (p&lt;0,05). У АЦЦП(+) пациентов чаще встречались воспалительные изменения проксимальных межфаланговых, пястнофаланговых, лучезапястных и плечевых суставов. Системные проявления РА на момент осмотра и в анамнезе статистически значимо чаще встречались у АЦЦП(+), чем у АЦЦП(–) больных – 32,9% и 17,7% соответственно. Из системных проявлений у АЦЦП(+) пациентов чаще отмечались ревматоидные узелки, при АЦЦП(–) РА выявлена тенденция к большей частоте нейропатии, склерита и эписклерита.</p></sec><sec><title>Выводы</title><p>Выводы. У пациентов с АЦЦП(–) субтипом РА менее выражены клинические признаки поражения суставов и признаки системного воспаления по сравнению с АЦЦП(+) пациентов. Однако смешанная картина манифестации, менее «яркое» течение заболевания, отсутствие характерных иммунологических биомаркеров обуславливают необходимость длительного и тщательного наблюдения данной группы. При этом субъективное восприятие тяжести болезни и нарушение функции из-за анкилозирования суставов у АЦЦП(+) и АЦЦП(–) больных существенно не различались.</p></sec></abstract><trans-abstract xml:lang="en"><p>The aim of the study was to study the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.</p><sec><title>Materials and methods</title><p>Materials and methods. The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the values of the ACPA, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease and therapy. The nature of the onset and course of the disease, the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices).</p></sec><sec><title>Results and discussion</title><p>Results and discussion. The study included 79 patients with ACPA-negative variant of RA and 79 with ACPA-positive. Age of patients (Me [IR], in years) with the ACPA(–) variant was 52 [39; 62], with the ACPA(+) – 54 [42; 62], the duration of the disease (in months) is 59 [23; 122] and 48 [17; 84] respectively. In ACPA(+) patients, higher disease activity was determined by the indices DAS28-CRP, DAS28-ESR, SDAI, CDAI, values of C-reactive protein and erythrocyte sedimentation rate, a greater number of painful and swollen joints (p&lt;0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(–) (17.7%). Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, a tendency to a higher frequency of neuropathy, scleritis and episcleritis was revealed in ACPA(–) patients.</p></sec><sec><title>Conclusion</title><p>Conclusion. In patients with ACPA(–) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less “bright” course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>антитела к циклическому цитруллинированному пептиду</kwd><kwd>ревматоидный артрит</kwd><kwd>АЦЦП-негативный ревматоидный артрит</kwd><kwd>серонегативный ревматоидный артрит</kwd><kwd>клинические особенности</kwd></kwd-group><kwd-group xml:lang="en"><kwd>anti-cyclic citrullinated peptide antibodies</kwd><kwd>rheumatoid arthritis</kwd><kwd>ACPA-negative rheumatoid arthritis</kwd><kwd>seronegative rheumatoid arthritis</kwd><kwd>clinical features</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ (ред.). Российские клинические рекомендации. Ревматология. М.:ГЭОТАР-Медиа;2020.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL (ed.). Rheumatology. Russian clinical recommendations. Moscow:GEOTAR-Media;2020 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Burgers LE, van Steenbergen HW, Ten Brinck RM, Huizinga TW, van der Helm-van Mil AH. Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: A longitudinal study in arthralgia during progression to clinical arthritis. Ann Rheum Dis. 2017;76(10):1751-1754. doi: 10.1136/annrheumdis-2017-211325</mixed-citation><mixed-citation xml:lang="en">Burgers LE, van Steenbergen HW, Ten Brinck RM, Huizinga TW, van der Helm-van Mil AH. Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: A longitudinal study in arthralgia during progression to clinical arthritis. Ann Rheum Dis. 2017;76(10):1751-1754. doi: 10.1136/annrheumdis-2017-211325</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Pertsinidou E, Manivel VA, Westerlind H, Klareskog L, Alfredsson L, Mathsson-Alm L, et al. Rheumatoid arthritis autoantibodies and their association with age and sex. Clin Exp Rheumatol. 2021;39(4):879-882.</mixed-citation><mixed-citation xml:lang="en">Pertsinidou E, Manivel VA, Westerlind H, Klareskog L, Alfredsson L, Mathsson-Alm L, et al. Rheumatoid arthritis autoantibodies and their association with age and sex. Clin Exp Rheumatol. 2021;39(4):879-882.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Boeters DM, Mangnus L, Ajeganova S, Lindqvist E, Svensson B, Toes REM, et al. The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical. Arthritis Res Ther. 2017;19(1):115. doi: 10.1186/s13075-017-1324-y</mixed-citation><mixed-citation xml:lang="en">Boeters DM, Mangnus L, Ajeganova S, Lindqvist E, Svensson B, Toes REM, et al. The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical. Arthritis Res Ther. 2017;19(1):115. doi: 10.1186/s13075-017-1324-y</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Arnold MB, Bykerk VP, Boire G, Haraoui BP, Hitchon C, Thorne C, et al.; CATCH Investigators. Are there differences between young- and older-onset early inflammatory arthritis and do these impact outcomes? An analysis from the CATCH cohort. Rheumatology (Oxford). 2014;53(6):1075-1086. doi: 10.1093/rheumatology/ket449</mixed-citation><mixed-citation xml:lang="en">Arnold MB, Bykerk VP, Boire G, Haraoui BP, Hitchon C, Thorne C, et al.; CATCH Investigators. Are there differences between young- and older-onset early inflammatory arthritis and do these impact outcomes? An analysis from the CATCH cohort. Rheumatology (Oxford). 2014;53(6):1075-1086. doi: 10.1093/rheumatology/ket449</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Nilsson J, Andersson MLE, Hafström I, Svensson B, Forslind K, Ajeganova S, et al. Influence of age and sex on disease course and treatment in rheumatoid arthritis. Open Access Rheumatol. 2021;13:123-138. doi: 10.2147/OARRR.S306378</mixed-citation><mixed-citation xml:lang="en">Nilsson J, Andersson MLE, Hafström I, Svensson B, Forslind K, Ajeganova S, et al. Influence of age and sex on disease course and treatment in rheumatoid arthritis. Open Access Rheumatol. 2021;13:123-138. doi: 10.2147/OARRR.S306378</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7(5):949-958. doi: 10.1186/ar1767</mixed-citation><mixed-citation xml:lang="en">van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7(5):949-958. doi: 10.1186/ar1767</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Ursum J, Bos WH, van Dillen N, Dijkmans BA, van Schaardenburg D. Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: A cohort study. Arthritis Res Ther. 2010;12(1):8. doi: 10.1186/ar2907</mixed-citation><mixed-citation xml:lang="en">Ursum J, Bos WH, van Dillen N, Dijkmans BA, van Schaardenburg D. Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: A cohort study. Arthritis Res Ther. 2010;12(1):8. doi: 10.1186/ar2907</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bergstra SA, Couto MC, Govind N, Chopra A, Salomon Escoto K, Murphy E, et al. Impact of the combined presence of erosions and ACPA on rheumatoid arthritis disease activity over time: Results from the METEOR registry. RMD Open. 2019;5(2):e000969. doi: 10.1136/rmdopen-2019-000969</mixed-citation><mixed-citation xml:lang="en">Bergstra SA, Couto MC, Govind N, Chopra A, Salomon Escoto K, Murphy E, et al. Impact of the combined presence of erosions and ACPA on rheumatoid arthritis disease activity over time: Results from the METEOR registry. RMD Open. 2019;5(2):e000969. doi: 10.1136/rmdopen-2019-000969</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, et al. The association of treatment response and joint damage with ACPA-status in recent-onset RA: A subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis. 2012;71(2):245-248. doi: 10.1136/annrheumdis-2011-200379</mixed-citation><mixed-citation xml:lang="en">van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, et al. The association of treatment response and joint damage with ACPA-status in recent-onset RA: A subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis. 2012;71(2):245-248. doi: 10.1136/annrheumdis-2011-200379</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Seegobin SD, Ma MH, Dahanayake C, Cope AP, Scott DL, Lewis CM, et al. ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: Secondary analysis of a randomized controlled trial. Arthritis Res Ther. 2014;16(1):13. doi: 10.1186/ar4439</mixed-citation><mixed-citation xml:lang="en">Seegobin SD, Ma MH, Dahanayake C, Cope AP, Scott DL, Lewis CM, et al. ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: Secondary analysis of a randomized controlled trial. Arthritis Res Ther. 2014;16(1):13. doi: 10.1186/ar4439</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Shpatz R, Braun-Moscovici Y, Balbir-Gurman A. ACPA antibodies titer at the time of rheumatoid arthritis diagnosis is not associated with disease severity. Isr Med Assoc J. 2021;23(10):646-650.</mixed-citation><mixed-citation xml:lang="en">Shpatz R, Braun-Moscovici Y, Balbir-Gurman A. ACPA antibodies titer at the time of rheumatoid arthritis diagnosis is not associated with disease severity. Isr Med Assoc J. 2021;23(10):646-650.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Boer AC, Boonen A, van der Helm-van Mil AHM. Is anticitrullinated protein antibody-positive rheumatoid arthritis still a more severe disease than anti-citrullinated protein antibody-negative rheumatoid arthritis? A longitudinal cohort study in rheumatoid arthritis patients diagnosed from 2000 onward. Arthritis Care Res (Hoboken). 2018;70(7):987-996. doi: 10.1002/acr.23497</mixed-citation><mixed-citation xml:lang="en">Boer AC, Boonen A, van der Helm-van Mil AHM. Is anticitrullinated protein antibody-positive rheumatoid arthritis still a more severe disease than anti-citrullinated protein antibody-negative rheumatoid arthritis? A longitudinal cohort study in rheumatoid arthritis patients diagnosed from 2000 onward. Arthritis Care Res (Hoboken). 2018;70(7):987-996. doi: 10.1002/acr.23497</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Farragher TM, Lunt M, Plant D, Bunn DK, Barton A, Symmons DP. Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies. Arthritis Care Res (Hoboken). 2010;62(5):664-675. doi: 10.1002/acr.20207</mixed-citation><mixed-citation xml:lang="en">Farragher TM, Lunt M, Plant D, Bunn DK, Barton A, Symmons DP. Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies. Arthritis Care Res (Hoboken). 2010;62(5):664-675. doi: 10.1002/acr.20207</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Mouterde G, Rincheval N, Lukas C, Daien C, Saraux A, Dieudé P, et al. Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort. Arthritis Res Ther. 2019;21(1):140. doi: 10.1186/s13075-019-1909-8</mixed-citation><mixed-citation xml:lang="en">Mouterde G, Rincheval N, Lukas C, Daien C, Saraux A, Dieudé P, et al. Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort. Arthritis Res Ther. 2019;21(1):140. doi: 10.1186/s13075-019-1909-8</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Katchamart W, Koolvisoot A, Aromdee E, Chiowchanwesa wakit P, Muengchan C. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment out-comes in patients with rheumatoid arthritis. Rheumatol Int. 2015;35(10):1693-1699. doi: 10.1007/s00296-015-3271-8</mixed-citation><mixed-citation xml:lang="en">Katchamart W, Koolvisoot A, Aromdee E, Chiowchanwesa wakit P, Muengchan C. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment out-comes in patients with rheumatoid arthritis. Rheumatol Int. 2015;35(10):1693-1699. doi: 10.1007/s00296-015-3271-8</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">del Val del Amo N, Ibanez Bosch R, Fito Manteca C, Gutierrez Polo R, Loza Cortina E. Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness. Clin Exp Rheumatol. 2006;24(3):281-286.</mixed-citation><mixed-citation xml:lang="en">del Val del Amo N, Ibanez Bosch R, Fito Manteca C, Gutierrez Polo R, Loza Cortina E. Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness. Clin Exp Rheumatol. 2006;24(3):281-286.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Barra L, Pope JE, Orav JE, Boire G, Haraoui B, Hitchon C, et al.; CATCH Investigators. Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis. J Rheumatol. 2014;41(12):2361-2369. doi: 10.3899/jrheum.140082</mixed-citation><mixed-citation xml:lang="en">Barra L, Pope JE, Orav JE, Boire G, Haraoui B, Hitchon C, et al.; CATCH Investigators. Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis. J Rheumatol. 2014;41(12):2361-2369. doi: 10.3899/jrheum.140082</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Nordberg LB, Lillegraven S, Lie E, Aga AB, Olsen IC, Hammer HB, et al.; ARCTIC working group. Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria. Ann Rheum Dis. 2017;76(2):341-345. doi: 10.1136/annrheumdis-2015-208873</mixed-citation><mixed-citation xml:lang="en">Nordberg LB, Lillegraven S, Lie E, Aga AB, Olsen IC, Hammer HB, et al.; ARCTIC working group. Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria. Ann Rheum Dis. 2017;76(2):341-345. doi: 10.1136/annrheumdis-2015-208873</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Choi S, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative study. PLoS One. 2018;13(4):e0195550. doi: 10.1371/journal.pone.0195550</mixed-citation><mixed-citation xml:lang="en">Choi S, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative study. PLoS One. 2018;13(4):e0195550. doi: 10.1371/journal.pone.0195550</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Jonsson MK, Hensvold AH, Hansson M, Aga AB, Sexton J, Mathsson-Alm L, et al. The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy. Arthritis Res Ther. 2018;20(1):146. doi: 10.1186/s13075-018-1635-7.</mixed-citation><mixed-citation xml:lang="en">Jonsson MK, Hensvold AH, Hansson M, Aga AB, Sexton J, Mathsson-Alm L, et al. The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy. Arthritis Res Ther. 2018;20(1):146. doi: 10.1186/s13075-018-1635-7.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao SS, Nikiphorou E, Young A, Kiely PDW. Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study. Rheumatol Int. 2022;42(4):621-629. doi: 10.1007/s00296-021-04931-2.</mixed-citation><mixed-citation xml:lang="en">Zhao SS, Nikiphorou E, Young A, Kiely PDW. Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study. Rheumatol Int. 2022;42(4):621-629. doi: 10.1007/s00296-021-04931-2.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Gadeholt O, Hausotter K, Eberle H, Klink T, Pfeil A. Differing X-ray patterns in seronegative and seropositive rheumatoid arthritis. Clin Rheumatol. 2019;38(9):2403-2410. doi: 10.1007/s10067-019-04602-5.</mixed-citation><mixed-citation xml:lang="en">Gadeholt O, Hausotter K, Eberle H, Klink T, Pfeil A. Differing X-ray patterns in seronegative and seropositive rheumatoid arthritis. Clin Rheumatol. 2019;38(9):2403-2410. doi: 10.1007/s10067-019-04602-5.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Grosse J, Allado E, Roux C, Pierreisnard A, Couderc M, Clerc-Urmes I, et al. ACPA-positive versus ACPA-negative rheumatoid arthritis: Two distinct erosive disease entities on radiography and ultrasonography. Rheumatol Int. 2020;40(4):615-624. doi: 10.1007/s00296-019-04492-5</mixed-citation><mixed-citation xml:lang="en">Grosse J, Allado E, Roux C, Pierreisnard A, Couderc M, Clerc-Urmes I, et al. ACPA-positive versus ACPA-negative rheumatoid arthritis: Two distinct erosive disease entities on radiography and ultrasonography. Rheumatol Int. 2020;40(4):615-624. doi: 10.1007/s00296-019-04492-5</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Joo YB, Park YJ, Park KS, Kim KJ. Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic progression in patients with rheumatoid arthritis. Clin Rheumatol. 2019;38(9):2423-2432. doi: 10.1007/s10067-019-04554-w</mixed-citation><mixed-citation xml:lang="en">Joo YB, Park YJ, Park KS, Kim KJ. Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic progression in patients with rheumatoid arthritis. Clin Rheumatol. 2019;38(9):2423-2432. doi: 10.1007/s10067-019-04554-w</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Forslind K, Ahlmén M, Eberhardt K, Hafström I, Svensson B; BARFOT Study Group. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: Role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004;63(9):1090-1095. doi: 10.1136/ard.2003.014233</mixed-citation><mixed-citation xml:lang="en">Forslind K, Ahlmén M, Eberhardt K, Hafström I, Svensson B; BARFOT Study Group. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: Role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004;63(9):1090-1095. doi: 10.1136/ard.2003.014233</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Mustila A, Korpela M, Haapala AM, Kautiainen H, Laasonen L, Möttönen T, et al. Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies. Clin Exp Rheumatol. 2011;29(3):500-505.</mixed-citation><mixed-citation xml:lang="en">Mustila A, Korpela M, Haapala AM, Kautiainen H, Laasonen L, Möttönen T, et al. Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies. Clin Exp Rheumatol. 2011;29(3):500-505.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Coffey CM, Crowson CS, Myasoedova E, Matteson EL, Davis JM 3rd. Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: Missing the window of opportunity. Mayo Clin Proc. 2019;94(11):2241-2248. doi: 10.1016/j.mayocp.2019.05.023</mixed-citation><mixed-citation xml:lang="en">Coffey CM, Crowson CS, Myasoedova E, Matteson EL, Davis JM 3rd. Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: Missing the window of opportunity. Mayo Clin Proc. 2019;94(11):2241-2248. doi: 10.1016/j.mayocp.2019.05.023</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Paalanen K, Puolakka K, Nikiphorou E, Hannonen P, Sokka T. Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study. Rheumatology (Oxford). 2021;14;60(5):2391-2395. doi: 10.1093/rheumatology/keaa623</mixed-citation><mixed-citation xml:lang="en">Paalanen K, Puolakka K, Nikiphorou E, Hannonen P, Sokka T. Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study. Rheumatology (Oxford). 2021;14;60(5):2391-2395. doi: 10.1093/rheumatology/keaa623</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Paalanen K, Rannio K, Rannio T, Asikainen J, Hannonen P, Sokka T. Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study. Clin Exp Rheumatol. 2019;37(1):37-43.</mixed-citation><mixed-citation xml:lang="en">Paalanen K, Rannio K, Rannio T, Asikainen J, Hannonen P, Sokka T. Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study. Clin Exp Rheumatol. 2019;37(1):37-43.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
