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Федеральное государственное бюджетное учреждение науки
Институт теоретической и экспериментальной биофизики
Российской академии наук


ООО "ИЦ КОМКОН"

Адрес редакции и реквизиты

192012, Санкт-Петербург, ул.Бабушкина, д.82 к.2, литера А, кв.378

ISSN 1999-6314


Клиническая медицина » Педиатрия •

Том: 24
Статья: « 15 »
Страницы:. 176-199
Опубликована в журнале: 25 марта 2023 г.
English version

Системный ювенильный идиопатический артрит и его биомаркеры (Обзор литературы)

Хальчицкий С.Е., Грачева Ю.А., Печальнова С.А., Буслов К.Г., Виссарионов С.В., Батоцыренова Е.Г., Комов Ю.В., Крецер Т.Ю., Кашуро В.А.

ФГБУ «Национальный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И. Турнера» Минздрава России
ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России
ФГБОУ ВО «Российский государственный педагогический университет им. А.И.Герцена»
ФГБГОУ ВО «Санкт-Петербургский государственный университет»


Резюме
Системный ювенильный идиопатический артрит (сЮИА) и его осложнение, синдром активации макрофагов (сЮИА-МAS), являются редкими, но иногда очень серьезными или даже критическими заболеваниями детского возраста, которые иногда могут характеризоваться неспецифическими клиническими признаками и симптомами в начале заболевания, такими как непрекращающаяся лихорадка, головная боль, сыпь или артралгия - что сопровождается повышенным уровнем реагентов острой фазы. Для правильного утвердительного диагноза необходимо исключить бактериальные или вирусные инфекции, новообразования и другие иммуноопосредованные воспалительные заболевания. Задержка в постановке диагноза приводит к позднему началу таргетной терапии. Набор биомаркеров полезен для того, чтобы отличить сЮИА или сЮИА-МАS от аналогичных клинических состояний, особенно при отсутствии артрита. Анализ биомаркеров должен быть доступен для пациентов, иметь приемлемые цены производства и приобретения для медицинских лабораторий, а также быть достаточно простым в определении, иметь высокую чувствительность и специфичность и коррелировать с патофизиологическими путями развития болезни. В настоящее время назрела необходимость определить наиболее значимые биомаркеры и их синергетическое взаимодействие для простого и точного распознавания сЮИА и сЮИА-МАS, чтобы немедленно ориентировать клиницистов в направлении правильной постановки диагноза, в прогнозировании исходов заболевания, реакции на лечение, и риска рецидивов. Биомаркеры сЮИА представляют собой в настоящее время захватывающую область исследований, особенно из-за гетерогенной природы синдромов цитокинового шторма (CSS) в эпоху COVID. Они должны быть выбраны с особой тщательностью - факт, поддерживаемый все более совершенным генетическим и патофизиологическим пониманием сЮИА, а также CSS - так, чтобы вскоре могли быть разработаны новые системы классификации для правильной дифференцировки сходных групп пациентов, но имеющих заболевания разного генеза. В обзоре представлены сведения о последних достижениях в разработке и применении биомаркеров при системном ювенильном идиопатическом артрите. Выполнялся поиск статей в PubMed, сочетающий заранее определенные ключевые слова, относящиеся к биомаркерам системного ЮИА, его осложнениям и сопутствующим заболеваниям.


Ключевые слова
ювенильный артрит, синдром активации макрофагов, биомаркеры, цитокины, хемокины, предикторы, ремиссия, рецидив, реакция на лечение


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Список литературы

1. Martini A. Systemic juvenile idiopathic arthritis. Autoimmun Rev. 2012; 12(1): 56-59.


2. Cimaz R. Systemic-onset juvenile idiopathic arthritis. Autoimmun Rev. 2016; 15(9): 931-934.


3. Vastert SJ, Kuis W, Grom AA. Systemic JIA: new developments in the understanding of the pathophysiology and therapy. Best Pract Res Clin Rheumatol. 2009; 23(5): 655-664.


4. Mellins ED, Mac Aubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011; 7(7) 416-426.


5. Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005; 201(9): 1479-1486.


6. Giancane G, Minoia F, Davì S, et al. IL-1 inhibition in systemic juvenile idiopathic arthritis. Frontiers Pharmacol. 2016; 7: 467.


7. Ruperto N, Brunner HI, Quartier P, et al. Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018 77(12): 1710-1719.


8. Haar NM, van Dijkhuizen EHP, Swart JF, et al. Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019; 71(7): 1163-1173.


9. Martini A. It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 2012; 71(9): 1437-1439.


10. Consolaro A, Varnier GC, Martini A, et al. Advances in biomarkers for paediatric rheumatic diseases. Nat Rev Rheumatol. 2015; 11(5): 265-275.


11. Gohar F, Kessel C, Lavric M, et al. Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks? Arthritis Res Ther. 2016; 18(1): 1.


12. Swart JF, De Roock S, Prakken BJ. Understanding inflammation in juvenile idiopathic arthritis: how immune biomarkers guide clinical strategies in the systemic onset subtype. Eur J Immunol. 2016; 46 (9): 2068-2077.


13. De Jager W, Hoppenreijs EPAH, Wulffraat NM, et al. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis. 2007; 66 (5): 589-598.


14. Jelušić M, LukićI K, Tambić-Bukovac L, et al. Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis. Clin Rheumatol. 2007; 26(8): 1332-1334.


15. Kudela H, Drynda S, Lux A, et al. Comparative study of Interleukin- 18 (IL-18) serum levels in adult onset Still?s disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity. BMC Rheumatol. 2019; 3(1): 1.


16. De Benedetti F, Brunner HI, Ruperto N, et al. Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med. 2012;367(25):2385-2395. .


17. Lerkvaleekul B, Vilaiyuk S. Early reduction of serum interleukin-6 levels as a predictor of clinical remission in systemic juvenile idiopathic arthritis. Asian Pacific J Allergy Immunol. 2019; 37(2): 116-122.


18. Vilaiyuk S, Lerkvaleekul B, Soponkanaporn S, et al. Correlations between serum interleukin 6, serum soluble interleukin 6 receptor, and disease activity in systemic juvenile idiopathic arthritis patients treated with or without tocilizumab. Cent Eur J Immunol. 2019; 44 (2): 150-158.


19. Shimizu M, Nakagishi Y, Yachie A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine. 2013; 61(2): 345-348.


20. Peng Y, Liu X, Duan Z, et al. The Association of Serum IL-10 Levels with the Disease Activity in Systemic-Onset Juvenile Idiopathic Arthritis Patients. Mediators Inflamm. 2021; 2021: 1-7.


21. Mizuta M, Shimizu M, Inoue N, et al. Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease. Mod Rheumatol. 2016; 26 (6): 929-932.


22. Saccomanno B, Tibaldi J, Minoia F, et al., Predictors of effectiveness of anakinra in systemic juvenile idiopathic arthritis. J Rheumatol. 2019; 46(4): 416-421.


23. Nigrovic PA, Mannion M, Prince FHM, et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011; 63(2): 545-555.


24. Pardeo M, Marafon DP, Insalaco A, et al. Anakinra in systemic juvenile idiopathic arthritis: a single-center experience. J Rheumatol. 2015; 42(8): 1523-1527.


25. Кашуро В.А., Батоцыренова Е.Г., Елаева Н.Л. и др. Динамика содержания нейротрофических факторов головного мозга при экспериментальной коме у крыс. Казанский медицинский журнал. 2013; 94 (5): 695-699.


26. Кашуро В.А., Батоцыренова Е.Г., Иванов М.Б. и др. Изучение нейротрофических маркеров при острых тяжелых отравлениях этанолом. Экспериментальная и клиническая фармакология. 2015. Т. 78.(S): С. 31.


27. Frosch M, Ahlmann M, Vogl T, et al. The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1β form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60(3): 883-891.


28. Holzinger D, Frosch M, Kastrup A, et al. The toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2012; 71(6): 974-980.


29. Shenoi S, Ou JN, Ni C, et al. Comparison of biomarkers for systemic juvenile idiopathic arthritis. Pediatr Res. 2015; 78(5): 554-559.


30. Wittkowski H, Frosch M, Wulffraat N, et al. S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin. Arthritis Rheum. 2008; 58(12): 3924-3931.


31. Vignola S, Picco P, Falcini F, et al. Serum and synovial fluid concentration of vascular endothelial growth factor in juvenile idiopathic arthritides. Rheumatology (Oxford). 2002; 41(6) 6 91-696.


32. Yamasaki Y, Takei S, Imanaka H, et al. S100A12 and vascular endothelial growth factor can differentiate Blau syndrome and familial Mediterranean fever from systemic juvenile idiopathic arthritis. Clin Rheumatol. 2019; 38(3): 835-840.


33. Aljaberi N, Tronconi E, Schulert G, et al. The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis. Pediatr Rheumatol. 2020; 18(1): 1.


34. Vastert SJ, De Jager W, Noordman BJ, et al. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study. Arthritis Rheumatol. 2014; 66(4): 1034-1043.


35. Shimizu M, Inoue N, Mizuta M, et al. Serum leucine-rich α2-glycoprotein as a biomarker for monitoring disease activity in patients with systemic juvenile idiopathic arthritis. J Immunol Res. 2019; 2019: 3140204.


36. Aoki C, Inaba Y, Choe H, et al. Discrepancy between clinical and radiological responses to tocilizumab treatment in patients with systemic-onset juvenile idiopathic arthritis. J Rheumatol. 2014; 41(6): 1171-1177.


37. Wilson DC, Marinov AD, Blair HC, et al. Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarker for systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2010; 62(8): 2510-2516.


38. Takahashi A, Mori M, Naruto T, et al. The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis. Mod Rheumatol. 2009; 19(3): 302-308.


39. Lee PY, Schulert GS, Canna SW, et al. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2019; 79(2): 225-231.


40.Tasaki Y, Shimizu M, Inoue N, et al. Disruption of vascular endothelial homeostasis in systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: the dynamic roles of angiopoietin-1 and −2. Cytokine. 2016; 80: 1-6.


41. Cai L, Zhang C, Wu J, et al. Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cell correlate with clinical manifestations in systemic juvenile idiopathic arthritis. Jt Bone Spine. 2019; 86(1): 61-68.


42. Nigrovic PA, Martínez-Bonet M, Thompson SD. Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification. Current Opin Rheumatol. 2019; 31(5): 401-410.


43. Vastert SJ, Nigrovic PA. Editorial: toward Personalized Treatment for Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2018; 70 (8): 1172-1174.


44. Ombrello MJ, Arthur VL, Remmers EF, et al., Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications. Ann Rheum Dis. 2017; 76(5): 906-913.


45. Ombrello MJ, Remmers EF, Tachmazidou I, et al. HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis. Proc Natl Acad Sci U S A. 2015; 112 (52): 15970-15975.


46. Kessel C, Hedrich CM, Foell D. Innately Adaptive or Truly Autoimmune: is There Something Unique About Systemic Juvenile Idiopathic Arthritis? Arthritis Rheumatol. 2020; 72(2): 210-219.


47. Arthur VL, Shuldiner E, Remmers EF, et al. IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin-1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2018; 70(8): 1319-1330.


48. Hinze C, Fuehner S, Kessel C, et al. Impact of IL1RN Variants on Response to Interleukin-1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2020; 72(3): 499-505.


49. Sun J, Feng M, Wu F, et al. Plasma miR-26a as a diagnostic biomarker regulates cytokine expression in systemic juvenile idiopathic arthritis. J Rheumatol. 2016;43(8):1607-1614.


50. Schulert GS, Fall N, Harley JB, et al. Monocyte MicroRNA Expression in Active Systemic Juvenile Idiopathic Arthritis Implicates MicroRNA-125a-5p in Polarized Monocyte Phenotypes. Arthritis Rheumatol. 2016; 68(9): 2300-2313.


51. Kamiya Y, Kawada J, Kawano Y, et al. Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis. ClinRheumatol. 2015; 34 (10): 1705-1712.


52. Ravelli A, Grom AA, Behrens EM, et al. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012; 13(4): 289-298.


53. Behrens EM, Beukelman T, Paessler M, et al. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol. 2007; 34(5): 1133-1138.


54. Ravelli A, Minoia F, Davì S, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: a European League Against Rheumatism/ American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborat. Arthritis Rheumatol. 2016; 68(3): 566-576.


55. Schulert G, Minoia F, Bohnsack J, et al. Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res. 2018;70(3):409-419. 56. Shimizu M, Nakagishi Y, Kasai K, et al. Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: the diagnostic significance of interleukin-18 and interleukin-6. Cytokine. 2012; 58(2): 287-294.


57. Shimizu M, Mizuta M, Okamoto N, et al. Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Pediatr Rheumatol. 2020; 18(1): 1-7.


58. Minoia F, Bovis F, Davì S, et al. Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2019; 78(10): 1357-1362.


59. Crayne C, Cron RQ. Pediatric macrophage activation syndrome, recognizing the tip of the Iceberg. Eur J Rheumatol. 2020; 7 (1): 13-20.


60. Schulert GS, Canna SW. Convergent pathways of the hyperferritinemic syndromes. Int Immunol. 2018; 30(5): 195-203.


61. Crayne CB, Albeituni S, Nichols KE, et al. The immunology of macrophage activation syndrome. Front Immunol. 2019; 10:119.


62. Sakumura N, Shimizu M, Mizuta M, et al. Soluble CD163, a unique biomarker to evaluate the disease activity, exhibits macrophage activation in systemic juvenile idiopathic arthritis. Cytokine. 2018; 110: 459-465.


63. Ruscitti P, Cipriani P, Di Benedetto P, et al. H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome. Clin Exp Immunol. 2018; 191(2): 220-228.


64. Ruscitti P, Cipriani P, Di Benedetto P, et al. Advances in immunopathogenesis of macrophage activation syndrome during rheumatic inflammatory diseases: toward new therapeutic targets? Expert Rev Clin Immunol. 2017; 13(11): 1041-1047.


65. Eloseily EMA, Minoia F, Crayne CB, et al. Ferritin to Erythrocyte Sedimentation Rate Ratio: simple Measure to Identify Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. ACR Open Rheumatol. 2019; 1(6): 345-349.


66. Mellins E, Macaubas C, Grom A. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011; 7(7): 416-426.


67. Pardeo M, Bracaglia C, De Benedetti F. Systemic juvenile idiopathic arthritis: new insights into pathogenesis and cytokine directed therapies. Best Pract Res Clin Rheumatol. 2017; 31(4): 505-516.


68. Bracaglia C, De Graaf K, Marafon DP, et al., Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterize patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2017; 76(1): 166-172.


69. Shimizu M, Inoue N, Mizuta M, et al. Characteristic elevation of soluble TNF receptor II : i ratio in macrophage activation syndrome with systemic juvenile idiopathic arthritis. Clin Exp Immunol. 2018; 191(3): 349-355.


70. Cifaldi L, Prencipe G, Caiello I, et al. Inhibition of natural killer cell cytotoxicity by interleukin-6: implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol. 2015; 67 (11): 3037-3046.


71.De Jager W, Vastert SJ, Beekman JM, et al. Defective phosphorylation of interleukin-18 receptor β causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60(9): 2782-2793.


72. Vandenhaute J, Wouters CH, Matthys P. Natural Killer Cells in Systemic Autoinflammatory Diseases: a Focus on Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome. Front Immunol. 2020; 10: 1-14.


73. De Benedetti F, Brogan P, Grom A, et al. Emapalumab, an interferon gamma-blocking monoclonal antibody, in patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). In: Proceedings of the EULAR Meeting Madrid. 2019.


74. Martini A. Are there new targets for juvenile idiopathic arthritis? Semin Arthritis Rheum. 2019; 49(3): S11-3.


75. Maschalidi S, Sepulveda FE, Garrigue A, et al. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016; 128(1): 60-71.


76. Das R, Guan P, Sprague L, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood. 2016; 127(13): 1666-1675.


77. Shimizu M, Nakagishi Y, Inoue N, et al., Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin Immunol. 2015; 160(2): 277-281.


78. Yasin S, Fall N, Brown RA, et al. IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome. Rheumatol (United Kingdom). 2020; 59(2): 361-366.


79.Canna SW, De JAA, Gouni S, et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 2014; 46(10): 1140-1146.


80. Weiss ES, Girard-Guyonvarc?h C, Holzinger D, et al. Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome. Blood. 2018; 131 (13): 1442-1455.


81. Prencipe G, Bracaglia C, De Benedetti F. Interleukin-18 in pediatric rheumatic diseases. Curr Opin Rheumatol. 2019; 31(5): 421-427.


82.Takakura M, Shimizu M, Irabu H, et al. Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Clin Immunol. 2019; 208: 108252.


83. Behrens EM, Beukelman T, Paessler M, et al. Clinical significance of serum CXCL9 levels as a biomarker for systemic juvenile idiopathic arthritis associated macrophage activation syndrome. Cytokine. 2019; 13(1): 182-187.


84. Groom J, Luster A. CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol. 2011; 89(2): 207-215.


85. Mizuta M, Shimizu M, Irabu H, et al. Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children. Rheumatology (Oxford). 2020; 60(1): 231-238.


86.Irabu H, Shimizu M, Kaneko S, et al., Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis during tocilizumab therapy. Pediatr Res. 2020; 88(6): 934-939.