clinvestКачественная клиническая практикаKachestvennaya Klinicheskaya Praktika = Good Clinical Practice2588-05192618-8473ООО «Издательство ОКИ10.37489/2588-0519-GCP-0009VNHDABclinvest-826Research ArticleВНУТРЕННИЕ БОЛЕЗНИINTERNAL MEDICINEБиомаркеры липополисахарид-ассоциированных  фенотипов у больных подагройBiomarkers of lipopolysaccharide-associated phenotypes in gout patientshttps://orcid.org/0000-0002-8960-602XБублейК. В.BubleyK. V.

Бублей  Константин  Викторович — ассистент кафедры внутренней медицины № 2 2-го медицинского факультета, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Konstantin V. Bubley — Assistant Professor of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

bubley.99@mail.ruhttps://orcid.org/0000-0001-9640-754XБелоглазовА. В.BeloglazovV. A.

Белоглазов Владимир Алексеевич — д. м. н., профессор, зав. кафедрой внутренней медицины № 2 2-го медицинского, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Vladimir A. Beloglazov — Dr. Sci. (Med.), professor, Head of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

biloglazov@mail.ruhttps://orcid.org/0000-0002-5486-7262ЯцковИ. А.YatskovI. A.

Яцков  Игорь  Анатольевич — к. м. н., доцент кафедры внутренней медицины № 2 2-го медицинского факультета, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Igor A. Yatskov — Cand. Sci. (Med.), associate professor, Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

egermd@yandex.ruhttps://orcid.org/0000-0003-4590-3580АгееваЕ. С.AgeevaE. S.

Агеева Елизавета Сергеевна — д. м. н., доцент кафедры медицинской биологии, зав. кафедрой медицинской биологии, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Elizabeth S. Ageeva — Dr. Sci. (Med.), Head of the Department of Biology, Associate Professor of the Department of Biology of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

ageevaeliz@rambler.ruhttps://orcid.org/0000-0001-8757-9585ГаффароваА. С.GaffarovaA. S.

Гаффарова Анифе Севриевна — ассистент кафедры внутренней медицины № 2 2-го медицинского факультета, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Anife S. Gaffarova — Assistant Professor of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

anife.gaffarova96@yandex.ruhttps://orcid.org/0000-0001-5904-986XУсаченкоЮ. В.UsachenkoYu. V.

Усаченко Юлия Владимировна — к. м. н., доцент кафедры внутренней медицины № 2 2-го медицинского факультета, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Yulia V. Usachenko — Candidate of Medical Sciences, Associate Professor of the Department of Internal Medicine No. 2 of the 2nd Medical Faculty of the V. I. Vernadsky Crimean Federal University, Order of the Red Banner of Labor

Simferopol

muravskaya_yuliya@mail.ruhttps://orcid.org/0000-0003-3429-0686ГорловА. А.GorlovA. A.

Горлов Александр Александрович — ассистент кафедры внутренней медицины № 2 2-го медицинского факультета, Ордена Трудового Красного Знамени Медицинский институт им. С. И. Георгиевского

Симферополь 

Alexander A. Gorlov — Assistant Professor of the Department of Internal Medicine No. 2 of the Order of the Red Banner of Labor of the S. I. Georgievsky Medical Institute

Simferopol

alexander_gorloff@mail.ruФГАОУ ВО «Крымский федеральный университет им. В. И. Вернадского»РоссияV. I. Vernadsky Crimean Federal UniversityRussian Federation202517122025049098Copyright © Бублей К.В., Белоглазов А.В., Яцков И.А., Агеева Е.С., Гаффарова А.С., Усаченко Ю.В., Горлов А.А., 20252025Бублей К.В., Белоглазов А.В., Яцков И.А., Агеева Е.С., Гаффарова А.С., Усаченко Ю.В., Горлов А.А.Bubley K.V., Beloglazov V.A., Yatskov I.A., Ageeva E.S., Gaffarova A.S., Usachenko Y.V., Gorlov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinvest.ru/jour/article/view/826

Подагра является хроническим метаболических заболеванием, занимающим значительное место среди глобальных хронических заболеваний. В 2020 году 55,8 миллиона человек во всём мире страдали подагрой, что соответствует 0,7% от всего человечества, и с каждым годом распространённость продолжает увеличиваться. Учитывая рост заболеваемости подагрой, возникает необходимость в разработке более персонализированных подходов к терапии пациентов с подагрой. Настоящее исследование посвящено выявлению различных подгрупп (фенотипов) пациентов с подагрой и описанию их особенностей на основе комплексного анализа иммунологических и метаболических биомаркеров в плазме.

С помощью кластерного анализа было идентифицировано три фенотипа:

Полученные данные позволяют предположить новые мишени для терапевтического воздействия, например путём влияния на проявления эндотоксинемии при подагре, на липополисахарид-связывающие системы и непосредственно на сам липополисахарид (ЛПС).

Gout is a chronic metabolic disease that occupies a significant place among chronic diseases worldwide. In 2020, 55.8 million people worldwide suffered from gout, corresponding to 0.7% of all mankind, and the prevalence continues to increase annually. Given the increasing incidence of gout, more personalized approaches to the treatment of patients with gout need to be developed. This study aimed to identify various subgroups (phenotypes) of gout patients and describe their characteristics based on a comprehensive analysis of plasma immunological and metabolic biomarkers.

Three phenotypes were identified using cluster analysis:

The data obtained suggest new targets for therapeutic effects, for example, by influencing the manifestations of endotoxinemia in gout, LPS-binding systems, and LPS itself.

липополисахаридподаграфенотипыэндотоксинемияЛСБBPIlipopolysaccharidegoutphenotypesendotoxinemiaLSBBPIReferencesChoi HK, Ford ES. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med. 2007 May;120(5):442-7. doi: 10.1016/j.amjmed.2006.06.040. PMID: 17466656.Choi HK, Ford ES. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med. 2007 May;120(5):442-7. doi: 10.1016/j.amjmed.2006.06.040. PMID: 17466656.Russo E, Verzola D, Cappadona F, et al. The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling. Vessel Plus. 2021;5:15. doi: 10.20517/2574-1209.2021.11.Russo E, Verzola D, Cappadona F, et al. The role of uric acid in renal damage - A history of inflammatory pathways and vascular remodeling. Vessel Plus. 2021;5:15. doi: 10.20517/2574-1209.2021.11.GBD 2021 Gout Collaborators. Global, regional, and national burden of gout, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024 Aug;6(8):e507-e517. doi: 10.1016/S2665-9913(24)00117-6.GBD 2021 Gout Collaborators. Global, regional, and national burden of gout, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2024 Aug;6(8):e507-e517. doi: 10.1016/S2665-9913(24)00117-6.Qi H, Sun M, Terkeltaub R, Merriman TR, et al. Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout. Arthritis Rheumatol. 2024 Jul;76(7):1130-1140. doi: 10.1002/art.42838.Qi H, Sun M, Terkeltaub R, Merriman TR, et al. Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout. Arthritis Rheumatol. 2024 Jul;76(7):1130-1140. doi: 10.1002/art.42838.Dalbeth N, Choi HK, Terkeltaub R. Review: Gout: A Roadmap to Approaches for Improving Global Outcomes. Arthritis Rheumatol. 2017 Jan;69(1):22-34. doi: 10.1002/art.39799.Dalbeth N, Choi HK, Terkeltaub R. Review: Gout: A Roadmap to Approaches for Improving Global Outcomes. Arthritis Rheumatol. 2017 Jan;69(1):22-34. doi: 10.1002/art.39799.Violi F, Cammisotto V, Bartimoccia S, et al. Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease. Nat Rev Cardiol. 2023 Jan;20(1):24-37. doi: 10.1038/s41569-022-00737-2.Violi F, Cammisotto V, Bartimoccia S, et al. Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease. Nat Rev Cardiol. 2023 Jan;20(1):24-37. doi: 10.1038/s41569-022-00737-2.Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996 Nov;4(11):430-5. doi: 10.1016/0966-842x(96)10057-3.Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996 Nov;4(11):430-5. doi: 10.1016/0966-842x(96)10057-3.Michelsen KS, Doherty TM, Shah PK, Arditi M. TLR signaling: an emerging bridge from innate immunity to atherogenesis. J Immunol. 2004 Nov 15;173(10):5901-7. doi: 10.4049/jimmunol.173.10.5901.Michelsen KS, Doherty TM, Shah PK, Arditi M. TLR signaling: an emerging bridge from innate immunity to atherogenesis. J Immunol. 2004 Nov 15;173(10):5901-7. doi: 10.4049/jimmunol.173.10.5901.Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009 Jun;49(6):1877-87. doi: 10.1002/hep.22848.Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009 Jun;49(6):1877-87. doi: 10.1002/hep.22848.Pang J, Xu W, Zhang X, et al. Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Jul;46(2):175-182. doi: 10.1111/apt.14119.Pang J, Xu W, Zhang X, et al. Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Jul;46(2):175-182. doi: 10.1111/apt.14119.Carpino G, Del Ben M, Pastori D, et al. Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD. Hepatology. 2020 Aug;72(2):470-485. doi: 10.1002/hep.31056.Carpino G, Del Ben M, Pastori D, et al. Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD. Hepatology. 2020 Aug;72(2):470-485. doi: 10.1002/hep.31056.Qi P, Li L, Zhang J, Ren L, Xie X. The dual regulatory effects of intestinal microorganisms and their metabolites in gouty arthritis pathogenesis: a balance between promotion and inhibition. Front Immunol. 2025 Jun 18;16:1591369. doi: 10.3389/fimmu.2025.1591369.Qi P, Li L, Zhang J, Ren L, Xie X. The dual regulatory effects of intestinal microorganisms and their metabolites in gouty arthritis pathogenesis: a balance between promotion and inhibition. Front Immunol. 2025 Jun 18;16:1591369. doi: 10.3389/fimmu.2025.1591369.Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72. doi: 10.2337/db06-1491.Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72. doi: 10.2337/db06-1491.Lim PS, Chang YK, Wu TK. Serum Lipopolysaccharide-Binding Protein is Associated with Chronic Inflammation and Metabolic Syndrome in Hemodialysis Patients. Blood Purif. 2019;47(1-3):28-36. doi: 10.1159/000492778.Lim PS, Chang YK, Wu TK. Serum Lipopolysaccharide-Binding Protein is Associated with Chronic Inflammation and Metabolic Syndrome in Hemodialysis Patients. Blood Purif. 2019;47(1-3):28-36. doi: 10.1159/000492778.Lv Q, Zhou J, Wang C, et al. A dynamics association study of gut barrier and microbiota in hyperuricemia. Front Microbiol. 2023 Nov 27;14:1287468. doi: 10.3389/fmicb.2023.1287468.Lv Q, Zhou J, Wang C, et al. A dynamics association study of gut barrier and microbiota in hyperuricemia. Front Microbiol. 2023 Nov 27;14:1287468. doi: 10.3389/fmicb.2023.1287468.Системная эндотоксинемия. Гомеостаз и общая патология / М.Ю. Яковлев. – М.: Наука, 2021. – 184 с. ISBN 978-5-02-040858-6.Systemic endotoxemia. Homeostasis and general pathology. Yakovlev MYu. Moscow: Nauka; 2021. (In Russ.). ISBN 978-5-02-040858-6.Schultz H, Weiss JP. The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease. Clin Chim Acta. 2007 Sep;384(1-2):12-23. doi: 10.1016/j.cca.2007.07.005.Schultz H, Weiss JP. The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease. Clin Chim Acta. 2007 Sep;384(1-2):12-23. doi: 10.1016/j.cca.2007.07.005.Aquino-Domínguez AS, de Los Ángeles Romero-Tlalolini M, Torres-Aguilar H, et al. Bactericidal/Permeability-Increasing Protein (BPI), a Novel Antimicrobial Molecule in Human Breast Milk with Immune Potential. Microorganisms. 2025 Jan 8;13(1):115. doi: 10.3390/microorganisms13010115.Aquino-Domínguez AS, de Los Ángeles Romero-Tlalolini M, Torres-Aguilar H, et al. Bactericidal/Permeability-Increasing Protein (BPI), a Novel Antimicrobial Molecule in Human Breast Milk with Immune Potential. Microorganisms. 2025 Jan 8;13(1):115. doi: 10.3390/microorganisms13010115.Guzmán-Beltrán S, Juárez E, Cruz-Muñoz BL, et al. Bactericidal Permeability-Increasing Protein (BPI) Inhibits Mycobacterium tuberculosis Growth. Biomolecules. 2024 Apr 13;14(4):475. doi: 10.3390/biom14040475.Guzmán-Beltrán S, Juárez E, Cruz-Muñoz BL, et al. Bactericidal Permeability-Increasing Protein (BPI) Inhibits Mycobacterium tuberculosis Growth. Biomolecules. 2024 Apr 13;14(4):475. doi: 10.3390/biom14040475.Pepe G, Corica D, Currò M, et al. Fasting and meal-related zonulin serum levels in a large cohort of obese children and adolescents. Front Endocrinol (Lausanne). 2024 Feb 8;15:1329363. doi: 10.3389/fendo.2024.1329363.Pepe G, Corica D, Currò M, et al. Fasting and meal-related zonulin serum levels in a large cohort of obese children and adolescents. Front Endocrinol (Lausanne). 2024 Feb 8;15:1329363. doi: 10.3389/fendo.2024.1329363.Tran N, Garcia T, Aniqa M, et al. Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States. Am J Biomed Sci Res. 2022;15(2):153-177.Tran N, Garcia T, Aniqa M, et al. Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States. Am J Biomed Sci Res. 2022;15(2):153-177.Sanjabi S, Oh SA, Li MO. Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. Cold Spring Harb Perspect Biol. 2017 Jun 1;9(6):a022236. doi: 10.1101/cshperspect.a022236.Sanjabi S, Oh SA, Li MO. Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. Cold Spring Harb Perspect Biol. 2017 Jun 1;9(6):a022236. doi: 10.1101/cshperspect.a022236.Sisto M, Ribatti D, Lisi S. Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT. Biomolecules. 2021 Feb 18;11(2):310. doi: 10.3390/biom11020310.Sisto M, Ribatti D, Lisi S. Organ Fibrosis and Autoimmunity: The Role of Inflammation in TGFβ-Dependent EMT. Biomolecules. 2021 Feb 18;11(2):310. doi: 10.3390/biom11020310.Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab. 2009 Aug;20(6):295-302. doi: 10.1016/j.tem.2009.03.005.Huang PL. eNOS, metabolic syndrome and cardiovascular disease. Trends Endocrinol Metab. 2009 Aug;20(6):295-302. doi: 10.1016/j.tem.2009.03.005.Li P, Zhang L, Zhang M, et al. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med. 2016 Apr;37(4):989-97. doi: 10.3892/ijmm.2016.2491.Li P, Zhang L, Zhang M, et al. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med. 2016 Apr;37(4):989-97. doi: 10.3892/ijmm.2016.2491.

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