Clinical and pathogenetic aspects of intestinal inflammation in patients with axial spondyloarthritis associated with Crohn’s disease
Abstract. Comorbidity of axial spondyloarthritis (AxSpA) and Crohn’s disease (CD) is conditioned by common mechanisms within the concept of intestinal-vascular barrier impairment. However, the role of noninvasive markers in assessing the correlation between intestinal inflammation and endothelial dysfunction in this comorbidity requires clarification.Davydov D.A., Marchenko V.N., Shchukina O.B., Fomin B.F., Kachanova T.L., Kuznetsova D.A., Lapin S.V., Rubinstein A.A., Lozovaya T.A.
The aim: to study the significance of fecal markers of inflammation and permeability in case of AxSpA, CD, and their combination.
Material and methods. 78 patients were examined: 22 with a combination of AxSpA and CD (group A), 29 with isolated AxSpA (group B), and 27 with isolated CD (group B). All the participants were assessed for fecal calprotectin (FC), zonulin, eosinophilic neurotoxin, serum hyaluronan, and syndecan-1concentrations using enzyme-linked immunosorbent assay (ELISA) methodic. The state of endothelial glycocalyx (EGc) and microcirculation were assessed using dark-field microscopy. Statistical analysis was supplemented by the construction of link graphs (systemic reconstruction).
Results. FC levels were significantly higher in groups A and B comparatively to group B (p = 0.013). In group A, a correlation was found between FC levels and markers of EGc thinning and decreased perfusion. Systemic reconstruction identified FC as a systemically important indicator in all groups. Common correlates of FC level were systemic inflammation and microcirculatory disorders (EGc thinning, decreased capillary count). The relationship between intestinal inflammation and functional status is specific to both forms of AxSpA. However, in case of CD-associated form, a unique direct correlation between FC and zonulin level and the presence of syndesmophytes has been established, distinguishing this phenotype from isolated AxSpA.
Conclusion. FC serves as an integral marker reflecting local intestinal inflammation and systemic dysfunction of the EGc. Study results confirm the role of gut-vascular barrier in the pathogenesis of comorbidity. Gut-vascular barrier dysfunction is of key importance in CD-associated AxSpA. A comprehensive assessment of biomarkers is promising for phenotyping and personalized therapy for these patients.
Keywords
axial spondyloarthritis
Crohn’s disease
fecal calprotectin
gut-vascular barrier
endothelial glycocalyx
microcirculation
systemic reconstruction
References
1. Клиническая ревматология. 3-е издание, переработанное и дополненное. Руководство для врачей. Под ред. В.И. Мазурова. М.: Е-ното. 2021; 696 с. (Mazurov VI, editor. Clinical Rheumatology. 3rd edition, revised and expanded. A Guide for Physicians. Moscow: E-noto. 2021; 696 pp. (In Russ.)). ISBN: 978-5-906023-30-2
2. Лила А.М., Дубинина Т.В., Древаль Р.О., Лапшина С.А., Заботина А.Н. Медико социальная значимость и расчет экономического бремени аксиального спондилоартрита в Российской Федерации. Современная ревматология. 2022;16(1):20–25. (Lila AM, Dubinina TV, Dreval RO, Lapshina SA, Zabotina AN. Medical and social significance and assessment of the economic burden of axial spondyloarthritis in the Russian Federation. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2022;16(1):20–25 (In Russ.)).
https://doi.org/10.14412/1996-7012-2022-1-20-25
3. Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S et al. Comprehensive association analyses of extraintestinal manifestations in inflammatory bowel disease. Gastroenterology. 2024;167(2):315–32.
PMID: 38490347. PMCID: PMC11193636. https://doi.org/10.1053/j.gastro.2024.02.026
4. Rios Rodriguez V, Duran TI, Torgutalp M, Lopez-Medina C, Dougados M, Kishimoto M et al. Comparing clinical profiles in spondyloarthritis with Crohn’s disease or ulcerative colitis: insights from the ASAS-PerSpA study. Rheumatol Adv Pract. 2024;8(2):rkae064.
PMID: 38807853. PMCID: PMC11132819. https://doi.org/10.1093/rap/rkae064
5. Симаненков В.И., Маев И.В., Ткачева О.Н., Алексеенко С.А., Андреев Д.Н., Бордин Д.С. с соавт. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):121–278. (Simanenkov VI, Maev IV, Tkacheva ON, Alekseenko SA, Andreev DN, Bordin DS et al. Increased epithelial permeability syndrome in clinical practice. Multidisciplinary national consensus. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2021;20(1):121–278 (In Russ.)).
https://doi.org/10.15829/1728-8800-2021-2758
6. Jiang C, Marinescu I, Seiler A, Karvonen M. IBD considerations in spondyloarthritis. Ther Adv Musculoskelet Dis. 2020;12:1721727X20939410.
PMID: 32695235. PMCID: PMC7350041. https://doi.org/10.1177/1759720X20939410
7. Karreman MC, Luime JJ, Hazes JMW, Weel AEAM. The prevalence and incidence of axial and peripheral spondyloarthritis in inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis. 2017;11(5):631–42.
PMID: 28453761. https://doi.org/10.1093/ecco-jcc/jjw199
8. Klingberg E, Strid H, Stahl A, Deminger A, Carlsten H, Ohman L, Forsblad-d’Elia H. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther. 2017;19(1):21.
PMID: 28148281. PMCID: PMC5289027. https://doi.org/10.1186/s13075-017-1223-2
9. Badran S, El-Darouti A, Abd El-Mawly M. Screening of silent inflammatory bowel disease in spondyloarthritis. Rheumatol Int. 2024;44(5):1–10.
https://doi.org/10.1016/j.ejr.2023.10.001
10. Benfaremo D, Luchetti MM, Gabrielli A. Biomarkers in inflammatory bowel disease-associated spondyloarthritis: State of the art and unmet needs. J Immunol Res. 2019;2019:8630871.
PMID: 31276001. PMCID: PMC6589275. https://doi.org/10.1155/2019/8630871
11. Ikonomidis I, Pavlidis G, Katogiannis K, Kapniari I, Theodoropoulos K, Kountouri A et al. Differences in coronary flow reserve and flow-mediated dilation between plaque psoriasis and psoriatic arthritis. Eur Heart J. 2022;43(2):ehac544.2643.
https://doi.org/10.1093/eurheartj/ehac544.2643
12. Triantafyllou C, Nikolaou M, Ikonomidis I, Bamias G, Kouretas D, Andreadou I et al. Effects of anti-inflammatory treatment and surgical intervention on endothelial glycocalyx, peripheral and coronary microcirculatory function and myocardial deformation in inflammatory bowel disease patients: A two-arms two-stage clinical trial. Diagnostics (Basel). 2021;11(6):993.
PMID: 34070768. PMCID: PMC8227308. https://doi.org/10.3390/diagnostics11060993
13. Claesson-Welsh L, Dejana E, McDonald DM. Permeability of the endothelial barrier: Identifying and reconciling controversies. Trends Mol Med. 2021;27(4):314–31.
PMID: 33309601. PMCID: PMC8005435. https://doi.org/10.1016/j.molmed.2020.11.006
14. de la Motte CA, Kessler SP. The role of hyaluronan in innate defense responses of the intestine. Int J Cell Biol. 2015;2015:481301.
PMID: 25922605. PMCID: PMC4397497. https://doi.org/10.1155/2015/481301
15. Van Praet L, Jans L, Carron P, Jacques P, Glorieus E, Colman R et al. Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: Results from the GIANT cohort. Ann Rheum Dis. 2014;73(6):1186–89.
PMID: 24276368. https://doi.org/10.1136/annrheumdis-2013-203854
About the Authors
Denis A. Davydov, MD, PhD (Medicine), assistant at the Department of hospital therapy with a course in allergology and immunology named after scademician M.V. Chernorutsky with a clinic, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St.E-mail: davydov.rheum@gmail.com
ORCID: https://orcid.org/0000-0002-5524-1616. Scopus Author ID: 57217159189. eLibrary SPIN: 1132-5294
Valery N. Marchenko, MD, Dr. Sci. (Medicine), professor of the Department of hospital therapy with a course in allergology and immunology named after Academician M.V. Chernorutsky with a clinic, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia, Honored Doctor of the Republic of North Ossetia-Alania. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St.
E-mail: marchvn@mail.ru
ORCID: https://orcid.org/0000-0002-2440-7222. eLibrary SPIN: 1711-4150. Scopus Author ID: 57223802954
Oksana B. Shchukina, MD, Dr. Sci. (Medicine), professor, Department of general medical practice (family medicine), Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St
E-mail: burmao@gmail.com
ORCID: https://orcid.org/0000-0001-8402-0743. eLibrary SPIN: 2733-9630. Scopus Author ID: 35761206900
Boris F. Fomin, Dr. Sci. (Engineering), professor, professor of the Department of automation and control processes, Vladimir Ulyanov (Lenin) ”LETI” Saint Petersburg State Electrotechnical University of the Ministry of Education and Science of Russia. Address: 197022, Saint Petersburg, 5 lit. F Professora Popova St.
E-mail: bfomin@mail.ru
ORCID: https://orcid.org/0000-0002-1611-6468. Scopus ID: 12805247000. eLibrary SPIN: 9214-9958
Tamara L. Kachanova, Dr. Sci. (Engineering), professor of the Department of automation and control processes, Vladimir Ulyanov (Lenin) ”LETI” Saint Petersburg State Electrotechnical University of the Ministry of Education and Science of Russia. Address: 197022, Saint Petersburg, 5 lit. F Professora Popova St.
Email: kachanova-tamara@mail.ru
ORCID: https://orcid.org/0000-0003-4494-7143. Scopus ID: 12805123900. eLibrary SPIN: 4679-0001
Daria A. Kuznetsova, MD, PhD (Medicine), leading researcher at the Laboratory of molecular diagnostics of the Scientific and Methodological Center for Molecular Medicine of the Ministry of Healthcare of Russia, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St.
E-mail: lariwar@mail.ru
ORCID: https://orcid.org/0000-0001-5318-354X. eLibrary SPIN: 6110-6168. Scopus Author ID: 57205585994
Sergey V. Lapin, MD, PhD (Medicine), head of the Department of autoimmune diseases diagnostics of the Scientific and Methodological Center for Molecular Medicine of the Ministry of Healthcare of Russia, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St.
E-mail: svlapin@mail.ru
ORCID: https://orcid.org/0000-0002-4998-3699. eLibrary SPIN: 9852-7501. Scopus Author ID: 7006205727
Artem A. Rubinshtein, MD, junior researcher at the Laboratory of cellular immunology of the Department of virology and immunology named after Academician A.A. Smorodintsev, Institute of Experimental Medicine. Address: 197022, Saint Petersburg, 12 lit. D Academician Pavlov St.
E-mail: arrubin6@mail.ru
ORCID: https://orcid.org/0000-0002-8493-5211. eLibrary SPIN: 6025-1790. Scopus Author ID: 57417440100
Tatyana A. Lozovaya, MD, PhD (Medicine), physician of the Department of functional diagnostics No. 1, Academician I. P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6–8 Lva Tolstogo St.
E-mail: lozota@inbox.ru
ORCID: https://orcid.org/0009-0004-6589-5754. eLibrary SPIN: 2592-8347
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