Ревматоидный артрит как клинико-иммунологический синдром: фокус на серонегативный субтип заболевания

Ревматоидный артрит (РА) – наиболее частое иммуновоспалительное (аутоиммунное) ревматическое заболевание (ИВРЗ), проявляющийся хроническим эрозивным артритом и системным поражением внутренних органов. В настоящее время РА рассматривается как синдром, характеризующийся клинической и патогенетической гетерогенностью, связанной с многообразием механизмов патологической активации врожденного и приобретенного иммунитета, определяющих вариабильность течения и исходов воспалительного процесса и эффективность терапии. На основании выявления или отсутствия IgM ревматоидного фактора (РФ) и антител к циклическим цитруллинированным пептидам (АЦЦП) РА условно подразделяется на два субтипа (фенотипа): серопозитивный РА и серонегативный РА, – однако благодаря совершенствованию методов лабораторной диагностики спектр аутоантител, выявляемых при РА, существенно увеличился. Диагностика серонегативного РА, основанная на классификационных (а не диагностических) критериях, может быть затруднена, особенно на ранних стадиях заболевания, и диагноз устанавливается только в процессе длительного наблюдения пациентов. Это усложняет своевременное назначение адекватной противовоспалительной терапии. В статье суммированы данные, касающиеся проблем генетической предрасположенности, иммунопатогенеза, биомаркеров, клинического спектра, инструментальной диагностики и фармакотерапии серонегативного РА.

1. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. doi: 10.1038/nrdp.2018.1

2. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-2219. doi: 10.1056/NEJMra1004965

3. Gravallese EM, Firestein GS. Rheumatoid arthritis – Common origins, divergent mechanisms. N Engl J Med. 2023;388(6):529-542. doi: 10.1056/NEJMra2103726

4. Насонов ЕЛ. Проблемы иммунопатологии ревматоидного артрита: эволюция болезни. Научно-практическая ревматология. 2017;55(3):277-294. doi: 10.14412/1995-4484-2017-277-294

5. Насонов ЕЛ. Фармакотерапия ревматоидного артрита: новая стратегия, новые мишени. Научно-практическая ревматология. 2017;55(4):409-419. doi: 10.14412/1995-4484-2017-409-419

6. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175-187. doi: 10.1136/annrheumdis-2017-211555

7. McGonagle D, Watad A, Savic S. Mechanistic immunological based classification of rheumatoid arthritis. Autoimmun Rev. 2018;17(11):1115-1123. doi: 10.1016/j.autrev.2018.06.001

8. Sokolova MV, Schett G, Steffen U. Autoantibodies in rheumatoid arthritis: Historical background and novel findings. Clin Rev Allergy Immunol. 2022;63(2):138-151. doi: 10.1007/s12016-021-08890-1

9. Volkov M, van Schie KA, van der Woude D. Autoantibodies and B cells: The ABC of rheumatoid arthritis pathophysiology. Immunol Rev. 2020;294(1):148-163. doi: 10.1111/imr.12829

10. Pouw JN, Leijten EFA, van Laar JM, Boes M. Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD). Clin Exp Immunol. 2021;203(2):160-173. doi: 10.1111/cei.13542

11. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi: 10.1002/art.27584

12. Wu CY, Yang HY, Lai JH. Anti-citrullinated protein antibodies in patients with rheumatoid arthritis: Biological effects and mechanisms of immunopathogenesis. Int J Mol Sci. 2020;21(11):4015. doi: 10.3390/ijms21114015

13. Catrina A, Krishnamurthy A, Rethi B. Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis. RMD Open. 2021;7(1):e001228. doi: 10.1136/rmdopen-2020-001228

14. Scherer HU, van der Woude D, Toes REM. From risk to chronicity: Evolution of autoreactive B cell and antibody responses in rheumatoid arthritis. Nat Rev Rheumatol. 2022;18(7):371-383. doi: 10.1038/s41584-022-00786-4

15. Lenti MV, Rossi CM, Melazzini F, Gastaldi M, Bugatti S, Rotondi M, et al. Seronegative autoimmune diseases: A challenging diagnosis. Autoimmun Rev. 2022;21(9):103143. doi: 10.1016/j.autrev.2022.103143

16. Moll JM. Seronegative arthropathies. J R Soc Med. 1983;76(6):445-448. doi: 10.1177/014107688307600601

17. Boeters DM, Gaujoux-Viala C, Constantin A, van der Helmvan Mil AHM. The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts. Semin Arthritis Rheum. 2017;47(2):170-174. doi: 10.1016/j.semarthrit.2017.04.009

18. Paalanen K, Puolakka K, Nikiphorou E, Hannonen P, Sokka T. Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study. Rheumatology (Oxford). 2021;60(5):2391-2395. doi: 10.1093/rheumatology/keaa623

19. Mease PJ, Bhutani MK, Hass S, Yi E, Hur P, Kim N. Comparison of clinical manifestations in rheumatoid arthritis vs. spondyloarthritis: A systematic literature review. Rheumatol Ther. 2022; 9(2):331-378. doi: 10.1007/s40744-021-00407-8

20. 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.

21. Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al.; T2T Expert Committee. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631-637. doi: 10.1136/ard.2009.123919

22. Matthijssen XME, Niemantsverdriet E, Huizinga TWJ, van der Helm-van Mil AHM. Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands. PLoS Med. 2020;17(9):e1003296. doi: 10.1371/journal.pmed.1003296

23. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328-2337. doi: 10.1016/S0140-6736(17)31472-1

24. Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: From triggering to targeting. Nat Rev Immunol. 2017;17(1):60-75. doi: 10.1038/nri.2016.124

25. Roodenrijs NMT, Welsing PMJ, van Roon J, Schoneveld JLM, van der Goes MC, Nagy G, et al. Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: A narrative review with systematic literature search. Rheumatology (Oxford). 2022;61(9):3552-3566. doi: 10.1093/rheumatology/keac114

26. De Stefano L, D’Onofrio B, Manzo A, Montecucco C, Bugatti S. The genetic, environmental, and immunopathological complexity of autoantibody-negative rheumatoid arthritis. Int J Mol Sci. 2021;22(22):12386. doi: 10.3390/ijms222212386

27. Li K, Wang M, Zhao L, Liu Y, Zhang X. ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation. EBioMedicine. 2022;83:104233. doi: 10.1016/j.ebiom.2022.104233

28. Дибров ДА. АЦЦП-негативный ревматоидный артрит – клинические и иммунологические особенности. Научно-практическая ревматология. 2022;60(3):314-326. doi: 10.47360/1995-4484-2022-314-326

29. Padyukov L. Genetics of rheumatoid arthritis. Semin Immunopathol. 2022;44(1):47-62. doi: 10.1007/s00281-022-00912-0

30. Frisell T, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J. Familial risks and heritability of rheumatoid arthritis: Role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 2013;65(11):2773-2782. doi: 10.1002/art.38097

31. Frisell T, Hellgren K, Alfredsson L, Raychaudhuri S, Klareskog L, Askling J. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: A register-based case-control study in Sweden. Ann Rheum Dis. 2016;75(1):183-189. doi: 10.1136/annrheumdis-2014-206133

32. Kirino Y, Remmers EF. Genetic architectures of seropositive and seronegative rheumatic diseases. Nat Rev Rheumatol. 2015;11(7):401-414. doi: 10.1038/nrrheum.2015.41

33. Padyukov L, Seielstad M, Ong RT, Ding B, Rönnelid J, Seddighzadeh M, et al.; Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study group. A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPAnegative rheumatoid arthritis. Ann Rheum Dis. 2011;70(2):259-265. doi: 10.1136/ard.2009.126821

34. Regueiro C, Casares-Marfil D, Lundberg K, Knevel R, AcostaHerrera M, Rodriguez-Rodriguez L, et al. HLA-B*08 identified as the most prominently associated major histocompatibility complex locus for anti-carbamylated protein antibody-positive/anticyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheumatol. 2021;73(6):963-969. doi: 10.1002/art.41630

35. Saevarsdottir S, Stefansdottir L, Sulem P, Thorleifsson G, Ferkingstad E, Rutsdottir G, et al.; Members of the DBDS Genomic Consortium; Danish RA Genetics Working Group; Swedish Rheumatology Quality Register Biobank Study Group (SRQb). Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset. Ann Rheum Dis. 2022;81(8):1085-1095. doi: 10.1136/annrheumdis-2021-221754

36. Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al. Trans-ancestry genome-wide association study identifies novel genetic mechanisms in rheumatoid arthritis. medRxiv. 2021;2021.12.01.21267132. doi: 10.1101/2021.12.01.21267132

37. Wei WH, Viatte S, Merriman TR, Barton A, Worthington J. Genotypic variability based association identifies novel non-additive loci DHCR7 and IRF4 in sero-negative rheumatoid arthritis. Sci Rep. 2017;7(1):5261. doi: 10.1038/s41598-017-05447-1

38. Yuan S, Li X, Lin A, Larsson SC. Interleukins and rheumatoid arthritis: Bi-directional Mendelian randomization investigation. Semin Arthritis Rheum. 2022;53:151958. doi: 10.1016/j.semarthrit.2022.151958

39. Chang C, Xu L, Zhang R, Jin Y, Jiang P, Wei K, et al. MicroRNA-mediated epigenetic regulation of rheumatoid arthritis susceptibility and pathogenesis. Front Immunol. 2022;13:838884. doi: 10.3389/fimmu.2022.838884

40. Jasemi S, Erre GL, Cadoni ML, Bo M, Sechi LA. Humoral response to microbial biomarkers in rheumatoid arthritis patients. J Clin Med. 2021;10(21):5153. doi: 10.3390/jcm10215153

41. Kronzer VL, Westerlind H, Alfredsson L, Crowson CS, Klareskog L, Holmqvist M, et al. Allergic conditions and risk of rheumatoid arthritis: A Swedish case-control study. RMD Open. 2022;8(1):e002018. doi: 10.1136/rmdopen-2021-002018

42. Morotti A, Sollaku I, Franceschini F, Cavazzana I, Fredi M, Sala E, et al. Systematic review and meta-analysis on the association of occupational exposure to free crystalline silica and rheumatoid arthritis. Clin Rev Allergy Immunol. 2022;62(2):333-345. doi: 10.1007/s12016-021-08846-5

43. Curtis JR, Jain A, Askling J, Bridges SL Jr, Carmona L, Dixon W, et al. A comparison of patient characteristics and outcomes in selected European and U.S. rheumatoid arthritis registries. Semin Arthritis Rheum. 2010;40(1):2-1r4.e1. doi: 10.1016/j.semarthrit.2010.03.003

44. Courvoisier DS, Chatzidionysiou K, Mongin D, Lauper K, Mariette X, Morel J, et al. The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: Results from a collaboration of 16 registries. Rheumatology (Oxford). 2021;60(2):820-828. doi: 10.1093/rheumatology/keaa393

45. Brinkmann GH, Norvang V, Norli ES, Grøvle L, Haugen AJ, Lexberg ÅS, et al. Treat to target strategy in early rheumatoid arthritis versus routine care – A comparative clinical practice study. Semin Arthritis Rheum. 2019;48(5):808-814. doi: 10.1016/j.semarthrit.2018.07.004

46. Balduzzi S, Scirè CA, Sakellariou G, Benaglio F, Bugatti S, Montecucco C, et al. In early inflammatory polyarthritis more intensive management according to the 2010 ACR/EULAR criteria leads to higher rates of clinical remission: Comparison of two cohorts treated according to different treat-to-target protocols. Clin Exp Rheumatol. 2017;35(3):401-405.

47. Elfving P, Kononoff A, Huhtakangas J, Kautiainen H, Savolainen E, Arstila L, et al. Incidence of seropositive rheumatoid arthritis in population-based studies in Northern Savo, Finland, during 1980–2020. Rheumatol Int. 2023;43(4):659-666. doi: 10.1007/s00296-022-05268-0

48. Enzer I, Dunn G, Jacobsson L, Bennett PH, Knowler WC, Silman A. An epidemiologic study of trends in prevalence of rheumatoid factor seropositivity in Pima Indians: evidence of a decline due to both secular and birth-cohort influences. Arthritis Rheum. 2002;46(7):1729-1734. doi: 10.1002/art.10360

49. Myasoedova E, Davis J, Matteson EL, Crowson CS. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014. Ann Rheum Dis. 2020;79(4):440-444. doi: 10.1136/annrheumdis-2019-216694

50. Hadwen B, Yu R, Cairns E, Barra L. Presence of autoantibodies in males and females with rheumatoid arthritis: A systematiceview and metaanalysis. J Rheumatol. 2022;49(7):663-671. doi: 10.3899/jrheum.211020

51. Matthjssen XME, Huizinga TWJ, van der Helm, van Mil AHM. Increasing incidence of autoantibody-negative RA is replicated and is partly explained by an aging population. Ann Rheum Dis. 2022;81:e69. doi: 10.1136/annrheumdis-2020-217609

52. Takanashi S, Takeuchi T, Kaneko Y. Effects of aging on rheumatoid factor and anticyclic citrullinated peptide antibody positivity in patients with rheumatoid arthritis. J Rheumatol. 2023;50(3):330-334. doi: 10.3899/jrheum.220526

53. 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

54. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-324. doi: 10.1002/art.1780310302

55. 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

56. Van Hoovels L, Studenic P, Sieghart D, Steiner G, Bossuyt X, Rönnelid J. Impact of autoimmune serology test results on RA classification and diagnosis. J Transl Autoimmun. 2022;5:100142. doi: 10.1016/j.jtauto.2022.100142

57. Hua C, Daien CI, Combe B, Landewe R. Diagnosis, prognosis and classification of early arthritis: Results of a systematic review informing the 2016 update of the EULAR recommendations for the management of early arthritis. RMD Open. 2017;3(1):e000406. doi: 10.1136/rmdopen-2016-000406

58. Norli ES, Brinkmann GH, Kvien TK, Bjørneboe O, Haugen AJ, Nygaard H, et al. Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort. Semin Arthritis Rheum. 2016;46(3):272-278. doi: 10.1016/j.semarthrit.2016.07.004

59. Leu Agelii M, Hafström I, Svensson B, Ajeganova S, Forslind K, Andersson M, et al. Misdiagnosis of rheumatoid arthritis in a longterm cohort of early arthritis based on the ACR-1987 classification criteria. Open Access Rheumatol. 2022;14:187-194. doi: 10.2147/OARRR.S372724

60. Combe B, Landewe R, Daien CI, Hua C, Aletaha D, ÁlvaroGracia JM, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis. 2017;76(6): 948-959. doi: 10.1136/annrheumdis-2016-210602

61. Krekeler M, Baraliakos X, Tsiami S, Braun J. High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis. RMD Open. 2022;8(2):e002383. doi: 10.1136/rmdopen-2022-002383

62. Paalanen K, Rannio K, Rannio T, Asikainen J, Hannonen P, Sokka T. Prevalence of calcium pyrophosphate deposition disease in a cohort of patients diagnosed with seronegative rheumatoid arthritis. Clin Exp Rheumatol. 2020;38(1):99-106.

63. Lewis MJ, Barnes MR, Blighe K, Goldmann K, Rana S, Hackney JA, et al. Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes. Cell Rep. 2019;28(9):2455-2470.e5. doi: 10.1016/j.celrep.2019.07.091

64. Humby F, Lewis M, Ramamoorthi N, Hackney JA, Barnes MR, Bombardieri M, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019;78(6):761-772. doi: 10.1136/annrheumdis-2018-214539

65. Vickovic S, Schapiro D, Carlberg K, Lötstedt B, Larsson L, Hildebrandt F, et al. Three-dimensional spatial transcriptomics uncovers cell type localizations in the human rheumatoid arthritis synovium. Commun Biol. 2022;5(1):129. doi: 10.1038/s42003-022-03050-3

66. Argyriou A, Wadsworth MH 2nd, Lendvai A, Christensen SM, Hensvold AH, Gerstner C, et al. Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis. Nat Commun. 2022;13(1):4046. doi: 10.1038/s41467-022-31519-6

67. Wu X, Liu Y, Jin S, Wang M, Jiao Y, Yang B, et al. Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis. Nat Commun. 2021;12(1):4977. doi: 10.1038/s41467-021-25246-7

68. Floudas A, Canavan M, McGarry T, Mullan R, Nagpal S, Veale DJ, et al. ACPA status correlates with differential immune profile in patients with rheumatoid arthritis. Cells. 2021;10(3):647. doi: 10.3390/cells10030647

69. Walker LSK. The link between circulating follicular helper T cells and autoimmunity. Nat Rev Immunol. 2022;22(9):567-575. doi: 10.1038/s41577-022-00693-5

70. Pratt AG, Swan DC, Richardson S, Wilson G, Hilkens CM, Young DA, et al. A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly in anti-citrullinated peptide antibody-negative disease. Ann Rheum Dis. 2012;71(8):1374-1381. doi: 10.1136/annrheumdis-2011-200968

71. Anderson AE, Pratt AG, Sedhom MA, Doran JP, Routledge C, Hargreaves B, et al. IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis. Ann Rheum Dis. 2016;75(2):466-473. doi: 10.1136/annrheumdis-2014-205850

72. van Oosterhout M, Bajema I, Levarht EW, Toes RE, Huizinga TW, van Laar JM. Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheum. 2008;58(1):53-60. doi: 10.1002/art.23148

73. Liang Z, Wang N, Shang L, Wang Y, Feng M, Liu G, et al. Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3. Front Immunol. 2022;13:939265. doi: 10.3389/fimmu.2022.939265

74. Mun S, Lee J, Park M, Shin J, Lim MK, Kang HG. Serum biomarker panel for the diagnosis of rheumatoid arthritis. Arthritis Res Ther. 2021;23(1):31. doi: 10.1186/s13075-020-02405-7

75. Yang ML, Sodré FMC, Mamula MJ, Overbergh L. Citrullination and PAD enzyme biology in type 1 diabetes – Regulators of inflammation, autoimmunity, and pathology. Front Immunol. 2021;12: 678953. doi: 10.3389/fimmu.2021.678953

76. Liu X, Zhu L, Liu H, Cai Q, Yun Z, Sun F, et al. Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added. Front Immunol. 2022;13:972012. doi: 10.3389/fimmu.2022.972012

77. Truglia S, Mancuso S, Capozzi A, Recalchi S, Riitano G, Longo A, et al. ‘Non-criteria antiphospholipid antibodies’: Bridging the gap between seropositive and seronegative antiphospholipid syndrome. Rheumatology. 2022;61(2):826-833. doi: 10.1093/rheumatology/keab414

78. Gómez-Bañuelos E, Fava A, Andrade F. An update on autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol. 2023;35(2):61-67. doi: 10.1097/BOR.0000000000000922

79. Martín-Nares E, Hernández-Molina G. Novel autoantibodies in Sjögren’s syndrome: A comprehensive review. Autoimmun Rev. 2019;18(2):192-198. doi: 10.1016/j.autrev.2018.09.003

80. Vílchez-Oya F, Balastegui Martin H, García-Martínez E, Corominas H. Not all autoantibodies are clinically relevant. Classic and novel autoantibodies in Sjögren’s syndrome: A critical review. Front Immunol. 2022;13:1003054. doi: 10.3389/fimmu.2022.1003054

81. Davies EJ, Jones GT, Sengupta R. Autoantibodies in ankylosing spondylitis: A systematic literature review. Rheumatology. 2022;61(Suppl 1): keac133.262. doi: 10.1093/rheumatology/keac133.262

82. Xu S, Zhang X, Chen Y, Ma Y, Deng J, Gao X, et al. Anti-CD74 antibodies in spondyloarthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. 2021;51(1):7-14. doi: 10.1016/j.semarthrit.2020.12.002

83. Ten Bergen LL, Petrovic A, Aarebrot AK, Appel S. Current knowledge on autoantigens and autoantibodies in psoriasis. Scand J Immunol. 2020;92(4):e12945. doi: 10.1111/sji.12945

84. Haro I, Sanmartí R, Gómara MJ. Implications of post-translational modifications in autoimmunity with emphasis on citrullination, homocitrullination and acetylation for the pathogenesis, diagnosis and prognosis of rheumatoid arthritis. Int J Mol Sci. 2022;23(24):15803. doi: 10.3390/ijms232415803

85. Moritz CP, Paul S, Stoevesandt O, Tholance Y, Camdessanché JP, Antoine JC. Autoantigenomics: Holistic characterization of autoantigen repertoires for a better understanding of autoimmune diseases. Autoimmun Rev. 2020;19(2):102450. doi: 10.1016/j.autrev.2019.102450

86. Rönnelid J, Hansson M, Mathsson-Alm L, Cornillet M, Reed E, Jakobsson PJ, et al. Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants. Ann Rheum Dis. 2018;77(2):203-211. doi: 10.1136/annrheumdis-2017-211782

87. Sieghart D, Platzer A, Studenic P, Alasti F, Grundhuber M, Swiniarski S, et al. Determination of autoantibody isotypes increases the sensitivity of serodiagnostics in rheumatoid arthritis. Front Immunol. 2018;9:876. doi: 10.3389/fimmu.2018.00876

88. Konig MF, Giles JT, Nigrovic PA, Andrade F. Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis. Ann Rheum Dis. 2016;75(11):2022-2028. doi: 10.1136/annrheumdis-2015-208529

89. Reed E, Hedström AK, Hansson M, Mathsson-Alm L, Brynedal B, Saevarsdottir S, et al. Presence of autoantibodies in “seronegative” rheumatoid arthritis associates with classical risk factors and high disease activity. Arthritis Res Ther. 2020;22(1):170. doi: 10.1186/s13075-020-02191-2

90. Sidiras P, Lechanteur J, Imbault V, Sokolova T, Durez P, Gangji V, et al. Human carbamylome description identifies carbamylated α2-macroglobulin and hemopexin as two novel autoantigens in early rheumatoid arthritis. Rheumatology (Oxford). 2022;61(7):2826-2834. doi: 10.1093/rheumatology/keab838

91. Moore RE, Wang T, Duvvuri B, Feser ML, Deane KD, Solomon JJ, et al. Prediction of erosive disease development by antimitochondrial antibodies in rheumatoid arthritis. Arthritis Rheumatol. 2023;75(6):890-899. doi: 10.1002/art.42428

92. Lönnblom E, Leu Agelii M, Sareila O, Cheng L, Xu B, Viljanen J, et al. Autoantibodies to disease-related proteins in joints as novel biomarkers for the diagnosis of rheumatoid arthritis. Arthritis Rheumatol. 2023 Jan 31. doi: 10.1002/art.42463

93. Bason C, Barbieri A, Martinelli N, Olivieri B, Argentino G, Bartoloni E, et al. Identification of a novel serological marker in seronegative rheumatoid arthritis using the peptide library approach. Front Immunol. 2021;12:753400. doi: 10.3389/fimmu.2021.753400

94. Colasanti T, Sabatinelli D, Mancone C, Giorgi A, Pecani A, Spinelli FR, et al. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. J Autoimmun. 2020;113:102470. doi: 10.1016/j.jaut.2020.102470

95. Poulsen TBG, Damgaard D, Jørgensen MM, Senolt L, Blackburn JM, Nielsen CH, et al. Identification of potential autoantigens in anti-CCP-positive and anti-CCP-negative rheumatoid arthritis using citrulline-specific protein arrays. Sci Rep. 2021;11(1):17300. doi: 10.1038/s41598-021-96675-z

96. Richter M, Krishnamurthy H, Posso S, Carlin J, Buckner J. Highthroughput testing for modified-protein antibodies in patients diagnosed with “seronegative” rheumatoid arthritis. Arthritis Rheumatol. 2021;73(Suppl 9). URL: https://acrabstracts.org/abstract/high-throughput-testing-for-modified-protein-antibodies-in-patients-diagnosed-with-seronegative-rheumatoid-arthritis/(Accessed: 29 April 2023).

97. Cunningham KY, Hur B, Gupta VK, Arment CA, Wright KA, Mason TG, et al. Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity. Sci Rep. 2023;13(1):5360. doi: 10.1038/s41598-023-32428-4

98. Li K, Mo W, Wu L, Wu X, Luo C, Xiao X, et al. Novel autoantibodies identified in ACPA-negative rheumatoid arthritis. Ann Rheum Dis. 2021;80(6):739-747. doi: 10.1136/annrheumdis-2020-218460

99. Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR, et al. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis. 2012;71(5):638-641. doi: 10.1136/annrheumdis-2011-200990

100. Hensvold A, Klareskog L. Towards prevention of autoimmune diseases: The example of rheumatoid arthritis. Eur J Immunol. 2021;51(8):1921-1933. doi: 10.1002/eji.202048952

101. 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

102. van Boheemen L, Ter Wee MM, Falahee M, Filer A, van BeersTas M, Finckh A, et al. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire: Predicting clinical arthritis development. Scand J Rheumatol. 2022 Sep 29:1-8. doi: 10.1080/03009742.2022.2116806

103. Loza MJ, Nagpal S, Cole S, Laird RM, Alcala A, Rao NL, et al. Serologic biomarkers of progression toward diagnosis of rheumatoid arthritis in active component military personnel. Arthritis Rheumatol. 2022;74(11):1766-1775. doi: 10.1002/art.42260

104. Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18. doi: 10.1136/ard-2022-223356

105. Насонов ЕЛ, Каратеев ДЕ, Чичасова НВ. Новые рекомендации по лечению ревматоидного артрита (EULAR, 2013): место метотрексата. Научно-практическая ревматология. 2014;52(1):8-26. doi: 10.14412/1995-4484-2014-8-26

106. Насонов ЕЛ. Метотрексат при ревматоидном артрите – 2015: новые факты и идеи. Научно-практическая ревматология. 2015;53(4):421-433. doi: 10.14412/1995-4484-2015-421-433

107. Wevers-de Boer K, Visser K, Heimans L, Ronday HK, Molenaar E, Groenendael JH, et al. Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study). Ann Rheum Dis. 2012;71(9): 1472-1477. doi: 10.1136/annrheumdis-2011-200736

108. Nordberg LB, Lillegraven S, Aga AB, Sexton J, Olsen IC, Lie E, et al. Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial. RMD Open. 2018;4(2):e000752. doi: 10.1136/rmdopen-2018-000752

109. Duong SQ, Crowson CS, Athreya A, Atkinson EJ, Davis JM 3rd, Warrington KJ, et al. Clinical predictors of response to methotrexate in patients with rheumatoid arthritis: A machine learning approach using clinical trial data. Arthritis Res Ther. 2022;24(1):162. doi: 10.1186/s13075-022-02851-5

110. Greenwood M, Shipa M, Yeoh SA, Roussou E, Mukerjee D, Ehrenstein MR. Methotrexate reduces withdrawal rates of TNF inhibitors due to ineffectiveness in rheumatoid arthritis but only in patients who are seropositive. Ann Rheum Dis. 2020;79(11):1516-1517. doi: 10.1136/annrheumdis-2020-217725

111. Hernández-Breijo B, Brenis CM, Plasencia-Rodríguez C, Martínez-Feito A, Novella-Navarro M, Pascual-Salcedo D, et al. Methotrexate reduces the probability of discontinuation of TNF inhibitors in seropositive patients with rheumatoid arthritis. A real-world data analysis. Front Med (Lausanne). 2021;8:692557. doi: 10.3389/fmed.2021.692557

112. Wientjes MHM, den Broeder AA, Welsing PMJ, Verhoef LM, van den Bemt BJF. Prediction of response to anti-TNF treatment using laboratory biomarkers in patients with rheumatoid arthritis: A systematic review. RMD Open. 2022;8(2):e002570. doi: 10.1136/rmdopen-2022-002570

113. Takeuchi T, Miyasaka N, Inui T, Yano T, Yoshinari T, Abe T, et al. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: A post hoc analysis of the RISING study. Arthritis Res Ther. 2017;19(1):194. doi: 10.1186/s13075-017-1401-2

114. Hambardzumyan K, Hermanrud C, Marits P, Vivar N, Ernestam S, Wallman JK, et al.; SWEFOT study group. Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: Results from the SWEFOT trial population. Scand J Rheumatol. 2019;48(5):362-366. doi: 10.1080/03009742.2019.1602670

115. Shipa MRA, Di Cicco M, Balogh E, Nitu NA, Mainuddin MD, Bhadauria N, et al. Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another TNFi or a biologic of different mode of action? Mod Rheumatol. 2022 Aug 3:roac086. doi: 10.1093/mr/roac086

116. Isaacs JD, Cohen SB, Emery P, Tak PP, Wang J, Lei G, et al. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: A meta-analysis. Ann Rheum Dis. 2013;72(3):329-36. doi: 10.1136/annrheumdis-2011-201117

117. Norris-Grey C, Cambridge G, Moore S, Reddy V, Leandro M. Long-term persistence of rituximab in patients with rheumatoid arthritis: An evaluation of the UCL cohort from 1998 to 2020. Rheumatology (Oxford). 2022;61(2):591-596. doi: 10.1093/rheumatology/keab248

118. Sokolove J, Schiff M, Fleischmann R, Weinblatt ME, Connolly SE, Johnsen A, et al. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016;75(4):709-714. doi: 10.1136/annrheumdis-2015-207942

119. Alten R, Mariette X, Flipo RM, Caporali R, Buch MH, Patel Y, et al. Retention of subcutaneous abatacept for the treatment of rheumatoid arthritis: Real-world results from the ASCORE study: an international 2-year observational study. Clin Rheumatol. 2022;41(8):2361-2373. doi: 10.1007/s10067-022-06176-1

120. Harrold LR, Connolly SE, Wittstock K, Zhuo J, Kelly S, Lehman T, et al. Baseline anti-citrullinated protein antibody status and response to abatacept or non-TNFi biologic/targeted-synthetic DMARDs: US observational study of patients with RA. Rheumatol Ther. 2022;9(2):465-480. doi: 10.1007/s40744-021-00401-0

121. Bird P, Hall S, Nash P, Connell CA, Kwok K, Witcombe D, et al. Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in phase III randomised clinical trials of tofacitinib. RMD Open. 2019;5(1):e000742. doi: 10.1136/rmdopen-2018-000742

122. Sugawara M, Fujieda Y, Noguchi A, Tanimura S, Shimizu Y, Nakagawa I, et al. Prediction of the intolerance or non-responder to Janus kinase inhibitors in patients with rheumatoid arthritis: A preliminary retrospective study with integrative cluster analysis. Clin Exp Rheumatol. 2022;40(9):1674-1680. doi: 10.55563/clinexprheumatol/czhc93

123. Jung JY, Lee E, Kim JW, Suh CH, Kim HA. Efficacy and drug retention of tofacitinib in rheumatoid arthritis: From the nationwide Korean College of Rheumatology Biologics registry. Clin Exp Rheumatol. 2022 Aug 31. doi: 10.55563/clinexprheumatol/6fcyza

124. Taylor PC, Alten R, Álvaro Gracia JM, Kaneko Y, Walls C, Quebe A, et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8(1): e001994. doi: 10.1136/rmdopen-2021-001994

125. Насонов ЕЛ, Лила АМ. Барицитиниб: новые возможности фармакотерапии ревматоидного артрита и других иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2020;58(3):304-316. doi: 10.14412/1995-4484-2020-304-316

126. Каратеев АЕ. Проблемы боли и качества жизни при ревматоидном артрите: фокус на барицитиниб. Научно-практическая ревматология. 2020;58(4):420-427. doi: 10.47360/1995-4484-2020-420-427

127. Dougados M, Taylor PC, Bingham CO 3rd, Fallon L, Brault Y, Roychoudhury S, et al. The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis. RMD Open. 2022;8(2):e002478. doi: 10.1136/rmdopen-2022-002478

128. Willemze A, Trouw LA, Toes RE, Huizinga TW. The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol. 2012;8(3):144-152. doi: 10.1038/nrrheum.2011.204

129. D’Onofrio B, van der Helm-van Mil A, Huizinga WJT, van Mulligen E. Inducibility or predestination? Queries and concepts around drug-free remission in rheumatoid arthritis. Expert Rev Clin Immunol. 2023;19(2):217-225. doi: 10.1080/1744666X.2023.2157814

130. Amaya-Amaya J, Calixto OJ, Saade-Lemus S, Calvo-Paramo E, Mantilla RD, Rojas-Villarraga A, et al. Does non-erosive rheumatoid arthritis exist? A cross-sectional analysis and a systematic literature review. Semin Arthritis Rheum. 2015;44(5):489-498. doi: 10.1016/j.semarthrit.2014.09.006

131. Andersson ML, Svensson B, Forslind K. Distribution of erosions in hands and feet at the time for the diagnosis of RA and during 8-year follow-up. Clin Rheumatol. 2021;40(5):1799-1810. doi: 10.1007/s10067-020-0465-x

132. Bugatti S, Bogliolo L, Manzo A, De Stefano L, Delvino P, Motta F, et al. Impact of anti-citrullinated protein antibodies on progressive systemic bone mineral density loss in patients with early rheumatoid arthritis after two years of treat-to-target. Front Immunol. 2021;12:701922. doi: 10.3389/fimmu.2021.701922

133. Svensson B, Andersson MLE, Gjertsson I, Hafström I, Ajeganova S, Forslind K. Erosion-free rheumatoid arthritis: clinical and conceptional implications – A BARFOT study. BMC Rheumatol. 2022;6(1):88. doi: 10.1186/s41927-022-00317-4

134. Boeters DM, Burgers LE, Sasso EH, Huizinga TWJ, van der Helm-van Mil AHM. ACPA-negative RA consists of subgroups: patients with high likelihood of achieving sustained DMARD-free remission can be identified by serological markers at disease presentation. Arthritis Res Ther. 2019;21(1):121. doi: 10.1186/s13075-019-1902-2

135. Verstappen M, Niemantsverdriet E, Matthijssen XME, le Cessie S, van der Helm-van Mil AHM. Early DAS response after DMARD-start increases probability of achieving sustained DMARD-free remission in rheumatoid arthritis. Arthritis Res Ther. 2020;22(1):276. doi: 10.1186/s13075-020-02368-9

136. Verstappen M, van Steenbergen HW, de Jong PHP, van der Helm-van Mil AHM. Unraveling heterogeneity within ACPA-negative rheumatoid arthritis: The subgroup of patients with a strong clinical and serological response to initiation of DMARD treatment favor disease resolution. Arthritis Res Ther. 2022;24(1):4. doi: 10.1186/s13075-021-02671-z

137. Cagnotto G, Jacobsson LTH, Rydell E, Eberhard A, Compagno M, Turesson C. Male sex predicts a favorable outcome in early ACPAnegative rheumatoid arthritis: Data from an observational study. J Rheumatol. 2022;49(9):990-997. doi: 10.3899/jrheum.211199

138. Schäfer M, Albrecht K, Kekow J, Rockwitz K, Liebhaber A, Zink A, et al. Factors associated with treatment satisfaction in patients with rheumatoid arthritis: Data from the biological register RABBIT. RMD Open. 2020;6(3):e001290. doi: 10.1136/rmdopen-2020-001290

139. Bugatti S, De Stefano L, Manzo A, Sakellariou G, Xoxi B, Montecucco C. Limiting factors to Boolean remission differ between autoantibody-positive and -negative patients in early rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211011826. doi: 10.1177/1759720X211011826

140. Ten Klooster PM, de Graaf N, Vonkeman HE. Association between pain phenotype and disease activity in rheumatoid arthritis patients: A non-interventional, longitudinal cohort study. Arthritis Res Ther. 2019;21(1):257. doi: 10.1186/s13075-019-2042-4

141. Duffield SJ, Miller N, Zhao S, Goodson NJ. Concomitant fibromyalgia complicating chronic inflammatory arthritis: A systematic review and meta-analysis. Rheumatology (Oxford). 2018;57(8):1453-1460. doi: 10.1093/rheumatology/key112

142. Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 2006;8(4):R133. doi: 10.1186/ar2022

143. Lahiri M, Luben RN, Morgan C, Bunn DK, Marshall T, Lunt M, et al. Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register – the EPIC-2-NOAR Study). Ann Rheum Dis. 2014;73(1): 219-226. doi: 10.1136/annrheumdis-2012-202481

144. Wesley A, Bengtsson C, Elkan AC, Klareskog L, Alfredsson L, Wedrén S; Epidemiological Investigation of Rheumatoid Arthritis Study Group. Association between body mass index and anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis: Results from a population-based case-control study. Arthritis Care Res (Hoboken). 2013;65(1):107-112. doi: 10.1002/acr.21749

145. Feng J, Chen Q, Yu F, Wang Z, Chen S, Jin Z, et al. Body mass index and risk of rheumatoid arthritis: A meta-analysis of observational studies. Medicine (Baltimore). 2016;95(8):e2859. doi: 10.1097/MD.0000000000002859

146. Juan S, Jiabi Z. Impact of obesity on the efficacy of different biologic agents in inflammatory diseases: A systematic review and meta-analysis. Joint Bone Spine. 2019;86(2):173-183. doi: 10.1016/j.jbspin.2018.03.007

147. Ogdie A, Liu M, Rebello S, Cronin A, Dube B, McLean R, et al. Characteristics of patients with seropositive or seronegative rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis: Data from the US-based corrona rheumatoid arthritis and psoriatic arthritis/spondyloarthritis (PsA/SpA) registries. Arthritis Rheumatol. 2019;71(Suppl 10). URL: https://acrabstracts.org/abstract/characteristics-of-patients-with-seropositive-or-seronegative-rheumatoid-arthritis-psoriatic-arthritis-or-axial-spondyloarthritis-data-from-the-us-based-corrona-rheumatoid-arthritisand-psoriatic-a/ (Accessed: 22 April 2023).

148. Coskun Benlidayi I. Fibromyalgia interferes with disease activity and biological therapy response in inflammatory rheumatic diseases. Rheumatol Int. 2020;40(6):849-858. doi: 10.1007/s00296-019-04506-2

149. Lwin MN, Serhal L, Holroyd C, Edwards CJ. Rheumatoid arthritis: The impact of mental health on disease: A narrative review. Rheumatol Ther. 2020;7(3):457-471. doi: 10.1007/s40744-020-00217-4

150. Bugatti S, De Stefano L, D’Onofrio B, Nicrosini A, Mauric E, di Lernia M, et al. Inflammatory correlates of the patient global assessment of disease activity vary in relation to disease duration and autoantibody status in patients with rheumatoid arthritis. Ann Rheum Dis. 2022;81(9):1206-1213. doi: 10.1136/annrheumdis-2022-222436

151. Насонов ЕЛ, Олюнин ЮА, Лила АМ. Ревматоидный артрит: проблемы ремиссии и резистентности к терапии. Научно-практическая ревматология. 2018;56(3):263-271. doi: 10.14412/1995-4484-2018-263-271

152. Tan Y, Buch MH. ‘Difficult to treat’ rheumatoid arthritis: current position and considerations for next steps. RMD Open. 2022;8(2):e002387. doi: 10.1136/rmdopen-2022-002387

153. Buch MH, Eyre S, McGonagle D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021;17(1):17-33. doi: 10.1038/s41584-020-00541-7

154. Merola JF, Espinoza LR, Fleischmann R. Distinguishing rheumatoid arthritis from psoriatic arthritis. RMD Open. 2018;4(2):e000656. doi: 10.1136/rmdopen-2018-000656

155. Osman N, Mohamed FI, Hassan AA. Kamel SR, Ahmed SS. Frequency of inflammatory back pain and sacroiliitis in Egyptian patients with rheumatoid arthritis. Egypt J Radiol Nucl Med. 2019;50:25. doi: 10.1186/s43055-019-0019-6

156. Nikiphorou E, Sjöwall C, Hannonen P, Rannio T, Sokka T. Long-term outcomes of destructive seronegative (rheumatoid) arthritis – Description of four clinical cases. BMC Musculoskelet Disord. 2016;17:246. doi: 10.1186/s12891-016-1067-y

157. Kelkka T, Savola P, Bhattacharya D, Huuhtanen J, Lönnberg T, Kankainen M, et al. Adult-onset anti-citrullinated peptide antibody-negative destructive rheumatoid arthritis is characterized by a disease-specific CD8+ T lymphocyte signature. Front Immunol. 2020;11:578848. doi: 10.3389/fimmu.2020.578848

158. Moon JS, Younis S, Ramadoss NS, Iyer R, Sheth K, Sharpe O, et al. Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Nat Commun. 2023;14(1):319. doi: 10.1038/s41467-022-35264-8

159. McGonagle D, Aydin SZ, Gül A, Mahr A, Direskeneli H. ‘MHC-I-opathy’-unified concept for spondyloarthritis and Behçet disease. Nat Rev Rheumatol. 2015;11(12):731-740. doi: 10.1038/nrrheum.2015.147

160. Насонов ЕЛ, Авдеева АС, Коротаева ТВ, Дубинина ТВ, Усачева ЮВ. Роль интерлейкина 17 в патогенезе ревматоидного артрита. Есть ли перспективы применения ингибиторов ИЛ-17? Научно-практическая ревматология. 2023;61(2):165-180. doi: 10.47360/1995-4484-2023-165-180

161. Насонов ЕЛ, Лила АМ. Ингибиторы Янус-киназ при иммуновоспалительных ревматических заболеваниях: новые возможности и перспективы. Научно-практическая ревматология. 2019;57(1):8-16. doi: 10.14412/1995-4484-2019-8-16

162. Petsch C, Araujo EG, Englbrecht M, Bayat S, Cavallaro A, Hueber AJ, et al. Prevalence of monosodium urate deposits in a population of rheumatoid arthritis patients with hyperuricemia. Semin Arthritis Rheum. 2016;45(6):663-668. doi: 10.1016/j.semarthrit.2015.11.014

163. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Goutassociated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-241. doi: 10.1038/nature04516

164. Mitrovic S, Fautrel B. Clinical phenotypes of adult-onset Still’s disease: New insights from pathophysiology and literature findings. J Clin Med. 2021;10(12):2633. doi: 10.3390/jcm10122633

165. Насонов ЕЛ, Файст Е. Болезнь Стилла взрослых: новые горизонты. Научно-практическая ревматология. 2021;59(6):645-665. doi: 10.47360/1995-4484-2021-643-663

166. Cutolo M, Cimmino MA, Sulli A. Polymyalgia rheumatica vs late-onset rheumatoid arthritis. Rheumatology (Oxford). 2009;48(2):93-95. doi: 10.1093/rheumatology/ken294

167. Caporali R, Montecucco C, Epis O, Bobbio-Pallavicini F, Maio T, Cimmino MA. Presenting features of polymyalgia rheumatica (PMR) and rheumatoid arthritis with PMR-like onset: A prospective study. Ann Rheum Dis. 2001;60(11):1021-1024. doi: 10.1136/ard.60.11.1021

168. Floris A, Piga M, Cauli A, Salvarani C, Mathieu A. Polymyalgia rheumatica: An autoinflammatory disorder? RMD Open. 2018;4(1):e000694. doi: 10.1136/rmdopen-2018-000694

169. Inanir A, Yigit S, Karakus N, Tekin S, Rustemoglu A. Association of MEFV gene mutations with rheumatoid factor levels in patients with rheumatoid arthritis. J Investig Med. 2013;61(3):593-596. doi: 10.2310/JIM.0b013e318280a96e

170. Koca SS, Etem EO, Isik B, Yuce H, Ozgen M, Dag MS, Isik A. Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid arthritis. Joint Bone Spine. 2010;77(1):32-35. doi: 10.1016/j.jbspin.2009.08.006

171. Cañete JD, Arostegui JI, Queiró R, Gratacós J, Hernández MV, Larrosa M, et al. An unexpectedly high frequency of MEFV mutations in patients with anti-citrullinated protein antibodynegative palindromic rheumatism. Arthritis Rheum. 2007;56(8):2784-2788. doi: 10.1002/art.22755

172. Cuervo A, Sanmartí R, Ramírez J, Castellanos-Moreira R, Inciarte-Mundo J, Aróstegui JI, et al. Palindromic rheumatism: Evidence of four subtypes of palindromic-like arthritis based in either MEFV or rheumatoid factor/ACPA status. Joint Bone Spine. 2021;88(6):105235. doi: 10.1016/j.jbspin.2021.105235

173. Tani Y, Kishi T, Miyamae T, Kawamoto M, Kawaguchi Y, Taniguchi A, et al. The evaluation of gene polymorphisms associated with autoinflammatory syndrome in patients with palindromic rheumatism complicated by intermittent hydrarthrosis. Clin Rheumatol. 2020;39(3):841-845. doi: 10.1007/s10067-019-04883-w

174. Zhong L, Song H, Wang W, Li J, Ma M. MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis. PLoS One. 2017;12(8):e0182967. doi: 10.1371/journal.pone.0182967

175. Özen S, Batu ED, Demir S. Familial Mediterranean fever: Recent developments in pathogenesis and new recommendations for management. Front Immunol. 2017;8:253. doi: 10.3389/fimmu.2017.00253

176. Алекберова ЗС, Насонов ЕЛ. Перспективы применения колхицина в медицине: новые данные. Научно-практическая ревматология. 2020;58(2):183-190. doi: 10.14412/1995-4484-2020-183-190

177. Насонов ЕЛ, Самсонов МЮ. Роль интерлейкина 1 в развитии заболеваний человека: фокус на анакинре (рецепторном антагонисте ИЛ-1). Научно-практическая ревматология. 2022; 60(3):280-298. doi: 10.47360/1995-4484-2022-280-298

178. Насонов ЕЛ. Ингибиция иммунных контрольных точек и аутоиммунитет: ревматологические проблемы. Научно-практическая ревматология. 2018;56(1):5-9. doi: 10.14412/1995-4484-2018-5-9

179. Dang QM, Watanabe R, Shiomi M, Fukumoto K, Nobashi TW, Okano T, et al. Rheumatic immune-related adverse events due to immune checkpoint inhibitors – A 2023 update. Int J Mol Sci. 2023;24(6):5643. doi: 10.3390/ijms24065643

180. Albayda J, Dein E, Shah AA, Bingham CO 3rd, Cappelli L. Sonographic findings in inflammatory arthritis secondary to immune checkpoint inhibition: A case series. ACR Open Rheumatol. 2019;1(5):303-307. doi: 10.1002/acr2.1026

181. Bronstein Y, Ng CS, Hwu P, Hwu WJ. Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am J Roentgenol. 2011;197(6):W992-W1000. doi: 10.2214/AJR.10.6198

182. Feist J, Murray A, Skapenko A, Schulze-Koops H. A Rare side effect of checkpoint inhibitor therapy-nivolumab-induced axial polyarthritis of the facet and costovertebral joints. Arthritis Rheumatol. 2019;71(11):1823. doi: 10.1002/art.41036

183. Cappelli LC, Darrah E, Shah AA, Bingham CO. Patients with checkpoint inhibitor-induced inflammatory arthritis do not become seropositive for anti-cyclic citrullinated peptide when followed over time. ACR Open Rheumatol. 2022;4(1):83-84. doi: 10.1002/acr2.11363

184. Ghosh N, Tiongson MD, Stewart C, Chan KK, Jivanelli B, Cappelli L, et al. Checkpoint inhibitor-associated arthritis: A systematic review of case reports and case series. J Clin Rheumatol. 2021;27(8):e317-e322. doi: 10.1097/RHU.0000000000001370

185. Cappelli LC, Bingham CO, Forde PM, Anagnostou V, Brahmer J, Lipson EJ, et al. Anti-RA33 antibodies are present in a subset of patients with immune checkpoint inhibitor-induced inflammatory arthritis. RMD Open. 2022;8(2):e002511. doi: 10.1136/rmdopen-2022-002511

186. Насонов ЕЛ. Абатацепт при ревматоидном артрите: новая форма, новые механизмы, новые возможности. Научно-практическая ревматология. 2015;53(5):522-541. doi: 10.14412/1995-4484-2015-522-541

187. Farisogullari B, Pinto AS, Machado PM. COVID-19-associated arthritis: An emerging new entity? RMD Open. 2022;8(2): e002026. doi: 10.1136/rmdopen-2021-002026

188. Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, et al. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021;595(7866):283-288. doi: 10.1038/s41586-021-03631-y

189. Damoiseaux J, Dotan A, Fritzler MJ, Bogdanos DP, Meroni PL, Roggenbuck D, et al. Autoantibodies and SARS-CoV2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies. Autoimmun Rev. 2022;21(3):103012. doi: 10.1016/j.autrev.2021.103012

190. Lacagnina MJ, Heijnen CJ, Watkins LR, Grace PM. Autoimmune regulation of chronic pain. Pain Rep. 2021;6(1): e905. doi: 10.1097/PR9.0000000000000905

191. Goebel A, Andersson D, Helyes Z, Clark JD, Dulake D, Svensson C. The autoimmune aetiology of unexplained chronic pain. Autoimmun Rev. 2022;21(3):103015. doi: 10.1016/j.autrev.2021.103015

192. Tsigalou C, Vallianou N, Dalamaga M. Autoantibody production in obesity: Is there evidence for a link between obesity and autoimmunity? Curr Obes Rep. 2020;9(3):245-254. doi: 10.1007/s13679-020-00397-8

193. de Jonge H, Iamele L, Maggi M, Pessino G, Scotti C. Anti-cancer auto-antibodies: Roles, applications and open issues. Cancers (Basel). 2021;13(4):813. doi: 10.3390/cancers13040813

194. Wang Y, Lloyd KA, Melas I, Zhou D, Thyagarajan R, Lindqvist J, et al. Rheumatoid arthritis patients display B-cell dysregulation already in the naïve repertoire consistent with defects in B-cell tolerance. Sci Rep. 2019;9(1):19995. doi: 10.1038/s41598-019-56279-0

195. Mahendra A, Yang X, Abnouf S, Adolacion JRT, Park D, Soomro S, et al. Beyond autoantibodies: Biologic roles of human autoreactive B cells in rheumatoid arthritis revealed by RNA-sequencing. Arthritis Rheumatol. 2019;71(4):529-541. doi: 10.1002/art.40772

196. Rönnelid J, Turesson C, Kastbom A. Autoantibodies in rheumatoid arthritis – Laboratory and clinical perspectives. Front Immunol. 2021;12:685312. doi: 10.3389/fimmu.2021.685312

197. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol. 2019;71(9):1400-1412. doi: 10.1002/art.40930