mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2024-4-66-73mrj-1622Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSСывороточный кальпротектин при васкулитах, ассоциированных с антинейтрофильными цитоплазматическими антителамиSerum calprotectin in vasculitis associated with antineutrophil cytoplasmic antibodieshttps://orcid.org/0000-0001-8864-7623ВоркельЕ. Н.VorkelE. N.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0003-3552-2522РешетнякТ. М.ReshetnyakT. M.

кафедра ревматологии 

115522, Москва, Каширское шоссе, 34А;125993, Москва, ул. Баррикадная, 2/1, стр. 1

Department of Rheumatology 

34A, Kashirskoe Shosse, Moscow 115522;2/1, Barrikadnaya Street, Build. 1, Moscow 125993

reshetnyak.tatjana@yandex.ruhttps://orcid.org/0000-0001-6685-7670НурбаеваК. С.NurbaevaK. S.

кафедра ревматологии 

115522, Москва, Каширское шоссе, 34А;125993, Москва, ул. Баррикадная, 2/1, стр. 1

Department of Rheumatology 

34A, Kashirskoe Shosse, Moscow 115522;2/1, Barrikadnaya Street, Build. 1, Moscow 125993

https://orcid.org/0000-0002-3246-1157ЧеркасоваМ. В.CherkasovaM. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0001-9933-5350ТарасоваГ. М.TarasovaG. M.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-4846-5531ЕгороваО. Н.EgorovaO. N.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-6068-3080ЛилаА. М.LilaA. M.

кафедра ревматологии 

115522, Москва, Каширское шоссе, 34А;125993, Москва, ул. Баррикадная, 2/1, стр. 1

Department of Rheumatology 

34A, Kashirskoe Shosse, Moscow 115522;2/1, Barrikadnaya Street, Build. 1, Moscow 125993

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaRussian Federation2024210820241846673Copyright © Воркель Е.Н., Решетняк Т.М., Нурбаева К.С., Черкасова М.В., Тарасова Г.М., Егорова О.Н., Лила А.М., 20242024Воркель Е.Н., Решетняк Т.М., Нурбаева К.С., Черкасова М.В., Тарасова Г.М., Егорова О.Н., Лила А.М.Vorkel E.N., Reshetnyak T.M., Nurbaeva K.S., Cherkasova M.V., Tarasova G.M., Egorova O.N., Lila A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/1622

Ассоциированные с антинейтрофильными цитоплазматическими антителами (АНЦА) системные васкулиты (АНЦА-СВ) – группа редких и потенциально тяжелых системных заболеваний. Поиск надежных методов оценки активности АНЦА-СВ остается актуальным. Среди показателей активации нейтрофильного звена, появившихся в клинической практике, выделяют уровень сывороточного кальпротектина (КЛП), который может быть маркером для мониторинга активности васкулита и выявления пациентов с риском рецидива заболевания. Цель исследования – оценить уровень сывороточного КЛП у пациентов с АНЦА-СВ. Материал и методы. В исследуемую группу включено 64 пациента (37 – с гранулематозом с полиангиитом, 11 – с эозинофильным гранулематозом с полиангиитом и 16 – с микроскопическим полиангиитом) в возрасте 18 лет и старше с достоверным диагнозом АНЦА-СВ. Контрольную группу составили 30 здоровых лиц. Для определения активности АНЦА-СВ использовали индекс BVAS; высокая активность соответствовала значению BVAS >3. Повреждение оценивали с помощью индекса VDI. В зависимости от активности АНЦА-СВ больные были разделены на две группы: с высокой (1-я группа, n=33) и низкой (2-я группа, n=31) активностью. Кроме общепринятых показателей, у всех пациентов с АНЦА-СВ и здоровых доноров исследовали уровень сывороточного КЛП. Результаты и обсуждение. Были выявлены статистически значимые различия (p<0,001) концентрации КЛП у пациентов с АНЦА-СВ в 1-й и 2-й группах. Отмечена значимая корреляция уровня КЛП с количеством лейкоцитов, нейтрофилов, отношением нейтрофилов к лимфоцитам (NLR), системным индексом воспаления (SII). Содержание КЛП в крови при AНЦА-СВ было связано с уровнем креатинина и не ассоциировалось со скоростью клубочковой фильтрации и мочевым осадком. Хотя уровень КЛП зависел от активности заболевания, он не коррелировал с острофазовыми показателями, включая СОЭ и концентрацию СРБ. Заключение. Уровень сывороточного КЛП значимо выше у пациентов с активным АНЦА-СВ и связан с индексами воспаления NLR и SII, что позволяет рассматривать возможность использования данного показателя для оценки активности заболевания.

Antineutrophil cytoplasmic antibody-associated systemic vasculitis (ANCA-SV) is a group of rare and potentially severe systemic diseases. The search for reliable methods to assess ANCA-SV activity remains relevant. Among the indicators of neutrophil activation that have emerged in clinical practice, the level of serum calprotectin (CLP) stands out, which can be a marker for monitoring vasculitis activity and identifying patients at risk of disease relapse. Objective: to determine serum CLP levels in patients with ANCA-SV. Material and methods. The study group comprised 64 patients (37 with granulomatosis with polyangiitis, 11 with eosinophilic granulomatosis with polyangiitis and 16 with microscopic polyangiitis) aged 18 years and older with a confirmed diagnosis of ANCA-SV. The control group consisted of 30 healthy individuals. ANCA-SV activity was determined using the BVAS index; high activity corresponded to a BVAS value of >3. Damage was assessed using the VDI index. Depending on ANCA-SV activity, patients were divided into two groups: high activity group (group 1, n=33) and low activity group (group 2, n=31). In addition to the generally accepted indicators, serum CLP levels were assessed in all patients with ANCA-SV and healthy donors. Results and discussion. Statistically significant differences (p<0.001) were found in CLP levels in patients with ANCA-SV in groups 1 and 2. A significant correlation was found between CLP concentration and leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory index (SII). Blood CLP levels in ANCA-SV were associated with creatinine levels and not with glomerular filtration rate and urinary sediment. Although CLP concentration depended on disease activity, it did not correlate with acute phase indicators, including ESR and CRP concentration. Conclusion. Serum CLP concentration is significantly higher in patients with active ANCA-SV and is related to NLR and SII inflammatory indices, so we consider the possibility of using this indicator to assess disease activity. 

васкулитассоциированный с антинейтрофильными цитоплазматическими антителамиактивностькальпротектинмаркеры воспалениянейтрофилыvasculitis associated with antineutrophil cytoplasmic antibodiesactivitycalprotectininflammatory markersneutrophilsСтатья подготовлена в рамках фундаментальной научной темы № 122040400024-7.The article has been conducted within basic scientific topic № 122040400024-7.ReferencesKitching AR, Anders HJ, Basu N, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug;6(1):71. doi: 10.1038/s41572-020-0204-y.Kitching AR, Anders HJ, Basu N, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug;6(1):71. doi: 10.1038/s41572-020-0204-y.Бекетова ТВ. Алгоритм диагностики системных васкулитов, ассоциированных с антинейтрофильными цитоплазматическими антителами. Терапевтический архив. 2018;90(5):13-21.Beketova TV. Diagnostic algorithm for antineutrophil cytoplasmic antibody-associated systemic vasculitis. Terapevticheskii arkhiv. 2018;90(5):13-21. (In Russ.)Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715.Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715.Tomasson G, Grayson PC, Mahr AD, et al. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis – a meta-analysis. Rheumatology (Oxford). 2012 Jan;51(1):100-9. doi: 10.1093/rheumatology/ker280.Tomasson G, Grayson PC, Mahr AD, et al. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis – a meta-analysis. Rheumatology (Oxford). 2012 Jan;51(1):100-9. doi: 10.1093/rheumatology/ker280.Wiik A. Clinical and pathophysiological significance of anti-neutrophil cytoplasmic autoantibodies in vasculitis syndromes. Mod Rheumatol. 2009;19(6):590-9. doi: 10.1007/s10165-009-0219-4.Wiik A. Clinical and pathophysiological significance of anti-neutrophil cytoplasmic autoantibodies in vasculitis syndromes. Mod Rheumatol. 2009;19(6):590-9. doi: 10.1007/s10165-009-0219-4.Walulik A, Lysak K, B aszkiewicz M, et al. The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies. Int J Mol Sci. 2023 Dec 7;24(24):17217. doi: 10.3390/ijms242417217.Walulik A, Lysak K, B aszkiewicz M, et al. The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies. Int J Mol Sci. 2023 Dec 7;24(24):17217. doi: 10.3390/ijms242417217.Базарный ВВ. Возможности автоматизированного анализа крови в оценке нейтрофильных гранулоцитов (обзор литературы). Клиническая лабораторная диагностика. 2023;68(11):686-693.Bazarnyi VV. Possibilities of automated cell blood count procedures in the evaluation of neutrophil granulocytes (review of literature). Klinicheskaya Laboratornaya Diagnostika. 2023;68(11):686-693. (In Russ.)Nacken W, Roth J, Sorg C, Kerkhoff C. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microsc Res Tech. 2003 Apr 15;60(6):569-80. doi: 10.1002/jemt.10299.Nacken W, Roth J, Sorg C, Kerkhoff C. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Microsc Res Tech. 2003 Apr 15;60(6):569-80. doi: 10.1002/jemt.10299.Romand X, Bernardy C, Nguyen MVC, et al. Systemic calprotectin and chronic inflammatory rheumatic diseases. Joint Bone Spine. 2019 Nov;86(6):691-698. doi: 10.1016/j.jbspin.2019.01.003.Romand X, Bernardy C, Nguyen MVC, et al. Systemic calprotectin and chronic inflammatory rheumatic diseases. Joint Bone Spine. 2019 Nov;86(6):691-698. doi: 10.1016/j.jbspin.2019.01.003.Manfredi M, van Hoovels L, Benucci M, et al. Circulating Calprotectin (cCLP) in autoimmune diseases. Autoimmun Rev. 2023 May;22(5):103295. doi: 10.1016/j.autrev.2023.103295.Manfredi M, van Hoovels L, Benucci M, et al. Circulating Calprotectin (cCLP) in autoimmune diseases. Autoimmun Rev. 2023 May;22(5):103295. doi: 10.1016/j.autrev.2023.103295.Frosch M, Strey A, Vogl T, et al. Myeloidrelated proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2000 Mar;43(3):628-37. doi: 10.1002/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X.Frosch M, Strey A, Vogl T, et al. Myeloidrelated proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2000 Mar;43(3):628-37. doi: 10.1002/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X.Viemann D, Barczyk K, Vogl T, et al. MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood. 2007 Mar 15;109(6):2453-60. doi: 10.1182/blood-2006-08-040444.Viemann D, Barczyk K, Vogl T, et al. MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood. 2007 Mar 15;109(6):2453-60. doi: 10.1182/blood-2006-08-040444.Pepper RJ, Hamour S, Chavele KM, et al. Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCAassociated vasculitis and glomerulonephritis. Kidney Int. 2013 Jun;83(6):1150-8. doi: 10.1038/ki.2013.2.Pepper RJ, Hamour S, Chavele KM, et al. Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCAassociated vasculitis and glomerulonephritis. Kidney Int. 2013 Jun;83(6):1150-8. doi: 10.1038/ki.2013.2.Anton-Pampols P, Martinez Valenzuela L, et al. Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163. Clin Kidney J. 2022 Dec 7;16(4):693-700. doi: 10.1093/ckj/sfac257.Anton-Pampols P, Martinez Valenzuela L, et al. Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163. Clin Kidney J. 2022 Dec 7;16(4):693-700. doi: 10.1093/ckj/sfac257.Romand X, Paclet MH, Chuong MV, et al. Serum calprotectin and renal function decline in ANCA-associated vasculitides: a post hoc analysis of MAINRITSAN trial. RMD Open. 2023 Oct;9(4):e003477. doi: 10.1136/rmdopen-2023-003477.Romand X, Paclet MH, Chuong MV, et al. Serum calprotectin and renal function decline in ANCA-associated vasculitides: a post hoc analysis of MAINRITSAN trial. RMD Open. 2023 Oct;9(4):e003477. doi: 10.1136/rmdopen-2023-003477.Martinez Valenzuela L, Draibe J, Quero Ramos M, et al. Calprotectin as a smoldering activity detection tool and renal prognosis biomarker in ANCA associated vasculitis. PLoS One. 2018 Oct 22;13(10): e0205982. doi: 10.1371/journal.pone.0205982.Martinez Valenzuela L, Draibe J, Quero Ramos M, et al. Calprotectin as a smoldering activity detection tool and renal prognosis biomarker in ANCA associated vasculitis. PLoS One. 2018 Oct 22;13(10): e0205982. doi: 10.1371/journal.pone.0205982.Van Hoovels L, Bossuyt X. Serum calprotectin as promising diagnostic aid in predicting relapse in proteinase 3-antineutrophil cytoplasmatic antibodies-associated vasculitis. J Lab Precis Med. 2017;2:10. doi: 10.21037/jlpm.2017.03.04.Van Hoovels L, Bossuyt X. Serum calprotectin as promising diagnostic aid in predicting relapse in proteinase 3-antineutrophil cytoplasmatic antibodies-associated vasculitis. J Lab Precis Med. 2017;2:10. doi: 10.21037/jlpm.2017.03.04.Michailidou D, Duvvuri B, Kuley R, et al. Neutrophil activation in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis. Arthritis Res Ther. 2022 Jun 29;24(1):160. doi: 10.1186/s13075-022-02849-z.Michailidou D, Duvvuri B, Kuley R, et al. Neutrophil activation in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis. Arthritis Res Ther. 2022 Jun 29;24(1):160. doi: 10.1186/s13075-022-02849-z.Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990 Aug; 33(8):1101-7. doi: 10.1002/art.1780330807.Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990 Aug; 33(8):1101-7. doi: 10.1002/art.1780330807.Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990 Aug;33(8): 1094-100. doi: 10.1002/art.1780330806.Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990 Aug;33(8): 1094-100. doi: 10.1002/art.1780330806.Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):315-320. doi: 10.1136/annrheumdis-2021-221795.Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):315-320. doi: 10.1136/annrheumdis-2021-221795.Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):309-314. doi: 10.1136/annrheumdis-2021-221794.Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):309-314. doi: 10.1136/annrheumdis-2021-221794.Suppiah R, Robson JC, Grayson PC, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):321-326. doi: 10.1136/annrheumdis-2021-221796.Suppiah R, Robson JC, Grayson PC, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):321-326. doi: 10.1136/annrheumdis-2021-221796.Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009 Dec;68(12):1827-32. doi: 10.1136/ard.2008.101279.Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009 Dec;68(12):1827-32. doi: 10.1136/ard.2008.101279.Exley AR, Bacon PA, Luqmani RA, et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997 Feb;40(2): 371-80. doi: 10.1002/art.1780400222.Exley AR, Bacon PA, Luqmani RA, et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997 Feb;40(2): 371-80. doi: 10.1002/art.1780400222.Thieblemont N, Wright HL, Edwards SW, Witko-Sarsat V. Human neutrophils in autoimmunity. Semin Immunol. 2016 Apr;28(2): 159-73. doi: 10.1016/j.smim.2016.03.004.Thieblemont N, Wright HL, Edwards SW, Witko-Sarsat V. Human neutrophils in autoimmunity. Semin Immunol. 2016 Apr;28(2): 159-73. doi: 10.1016/j.smim.2016.03.004.Pepper RJ, Draibe JB, Caplin B, et al. Association of Serum Calprotectin (S100A8/A9) Level with Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic AntibodyAssociated Vasculitis. Arthritis Rheumatol. 2017 Jan;69(1):185-193. doi: 10.1002/art.39814.Pepper RJ, Draibe JB, Caplin B, et al. Association of Serum Calprotectin (S100A8/A9) Level with Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic AntibodyAssociated Vasculitis. Arthritis Rheumatol. 2017 Jan;69(1):185-193. doi: 10.1002/art.39814.Liu C. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance. Open Life Sci. 2024 Feb 5;19(1):20220823. doi: 10.1515/biol-2022-0823.Liu C. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance. Open Life Sci. 2024 Feb 5;19(1):20220823. doi: 10.1515/biol-2022-0823.Lee LE, Pyo JY, Ahn SS, et al. Systemic inflammation response index predicts allcause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Int Urol Nephrol. 2021 Aug;53(8):1631-1638. doi: 10.1007/s11255-020-02777-4.Lee LE, Pyo JY, Ahn SS, et al. Systemic inflammation response index predicts allcause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Int Urol Nephrol. 2021 Aug;53(8):1631-1638. doi: 10.1007/s11255-020-02777-4.Bai X, Xu PC, Chen T, et al. The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis. BMC Immunol. 2022 Sep 10;23(1):42. doi: 10.1186/s12865-022-00513-4.Bai X, Xu PC, Chen T, et al. The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis. BMC Immunol. 2022 Sep 10;23(1):42. doi: 10.1186/s12865-022-00513-4.

The authors declare that there are no conflicts of interest present.