ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2023.84.06ymj-276Research ArticleМЕТОДЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯMETHODS OF DIAGNOSIS AND TREATMENTСывороточные биомаркеры при разных типах фиброза легкихSerum biomarkers in different types of pulmonary fibrosishttps://orcid.org/0000-0002-9749-7070ЗулкарнеевР. Х.ZulkarneevR. Kh.

Зулкарнеев  Рустэм Халитович – д.м.н., проф. 

 Zulkarneev  Rustem Khalitovich – PhD in Medicine, Professor, Department of Internal Medicine

zurustem@mail.ruhttps://orcid.org/0000-0001-6522-8530ЗулкарнеевШ. Р.ZulkarneevSh. R.

Зулкарнеев Шамиль Рустэмович – студент

Zulkarneev Shamil Rustemovich – student

zulkarneev.shamil@gmail.comhttps://orcid.org/0000-0002-1695-5173КорытинаГ. Ф.KorytinaG. F.

Корытина  Гульназ Фаритовна – д.б.н., проф.; гл.н.с. 

Korytina Gulnaz Faritovna – PhD in Biological Sciences, Professor, Department of Biology;  Head of Physiological Genetics Laboratory 

guly_kory@mail.ruhttps://orcid.org/0000-0001-9596-7342ГибадуллинИ. А.GibadullinI. A.

 Гибадуллин Иршат Асхатович – аспирант, врач клиники БГМУ

Gibadullin Irshat Askhatovich – postgraduate student, Department of Hospital Surgery, doctor of the Department of Thoracic Surgery, BSMU Clinic

irshatg93@gmail.comhttps://orcid.org/0000-0002-2435-8141АвзалетдиновА. М.AvzaletdinovA. M.

Авзалетдинов  Артур Марсович – д.м.н., проф., зав. отд. клиники БГМУ

Avzaletdinov Artur Marsovich – PhD in Medicine, Professor, Department of Hospital Surgery,  Head of Thoracic Surgery Department, BSMU Clinic

irshatg93@gmail.comhttps://orcid.org/0000-0002-5087-393XКозыреваЛ. С.KozyrevaL. S.

Козырева  Лилия Сергеевна – к.м.н., зав. отд. клиники БГМУ

 Kozyreva Lilia Sergeevna – MD in Medicine, Head of Pulmonology Department

https://orcid.org/0000-0002-3954-2216ГимазоваА. И.GimazovaA. I.

Гимазова Алия Илнуровна – врач

Gimazova Aliya Ilnurovna – doctor, Department of Thoracic Surgery

aliya32.ru@mail.ruhttps://orcid.org/0000-0003-2386-6707ЗагидуллинН. Ш.ZagidullinN. Sh.

Загидуллин Науфаль Шамильевич – д.м.н., зав. кафедрой БГМУ

Zagidullin  Naufal Shamilevich – PhD in Medicine, Head of the Department of Internal Medicine

 450008, Ufa, Lenina St.

znaufal@mail.ruБашкирский гос. медицин. ун-т МЗ РФРоссияBashkir State Medical UniversityRussian FederationБашкирский гос. медицин. ун-т МЗ РФ; ИБГ УФИЦ РАНРоссияBashkir State Medical University; Institute of Biochemistry and GeneticsRussian FederationБашкирский гос. медицин. ун-т МЗ РФРоссияBashkir State Medical University ClinicRussian FederationГос. Новосибирская обл. клинич. б-цаРоссияState Novosibirsk Regional Clinical HospitalRussian Federation202306022025042427Copyright © Зулкарнеев Р.Х., Зулкарнеев Ш.Р., Корытина Г.Ф., Гибадуллин И.А., Авзалетдинов А.М., Козырева Л.С., Гимазова А.И., Загидуллин Н.Ш., 20252025Зулкарнеев Р.Х., Зулкарнеев Ш.Р., Корытина Г.Ф., Гибадуллин И.А., Авзалетдинов А.М., Козырева Л.С., Гимазова А.И., Загидуллин Н.Ш.Zulkarneev R.K., Zulkarneev S.R., Korytina G.F., Gibadullin I.A., Avzaletdinov A.M., Kozyreva L.S., Gimazova A.I., Zagidullin N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/276

Целью исследования было изучение особенностей легочного фиброза (ЛФ) на основе сывороточных биомаркеров у больных с идиопатическим ЛФ (ИЛФ) и COVID-19-ассоциированным фиброзом. Была исследована концентрация в сыворотке биомаркеров CA15-3, LOXL2, TGFBR3 и периостина у пациентов с ИЛФ, с COVID-19-ассоциированным фиброзом легких и в контрольной группе. Нами были выявлены значимые различия между уровнями в плазме LOXL2 в группе ИЛФ и КГ, группы ИЛФ и COVID-19-ассоциированного ЛФ. При ROC-анализе получены значения оптимальных точек разделения групп по уровню LOXL2 и периостина в сыворотке крови, что позволяет дифференцировать разные типы фиброза легких.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown origin with an average life expectancy of 3-5 years after diagnosis. The disease is accompanied by progressive pulmonary fibrosis, decreased lung function, poor response to therapy and early mortality. Various biomarkers, including serum biomarkers, are used for timely and differential diagnosis of idiopathic pulmonary fibrosis (IPF) and COVID-19-associated pulmonary fibrosis (PF), predicting the course of the disease and assessing the effectiveness of specific therapy. Target was to investigate the features of pulmonary fibrosis based on serum biomarkers in patients with ILF and COVID-19-associated fibrosis. Methods. Changes in serum concentrations of biomarkers CA15-3, LOXL2, TGFBR3 and periostin in patients with ILF (n=10), COVID-19-associated pulmonary fibrosis and controls were investigated. Results. Significant differences were found between LOXL2 concentrations in the control and ILF groups (p=0.003), ILF and COVID-19-associated fibrosis groups (p=0.036) and between periostin concentrations in the control and ILF groups (p=0.042). ROC analysis for LOXL2 revealed: in the ILF and control groups AUC=0.854 (95% CI 0.693-1.0; p<0.0001), with a sensitivity of 80.0% and specificity of 76.9%; in the ILF and COVID-19-associated LF groups AUC=0.773 (95% CI 0.556-0.989; p=0.014) with a sensitivity of 99.0% and specificity of 63.6%. For periostin: AUC=0.692 (95% CI 0.469-0.916; p=0.092) with a sensitivity of 50.0% and specificity of 84.6%. Correlation analysis in the pooled group showed a significant correlation for CA15-3 and periostin (rs=0.383; 95% CI 0.042-0.645; p=0.025), LOXL2 and periostin (rs=0.509; 95% CI 0.196-0.727; p=0.002), TGFBR3 and CA15-3 (rs=0.347; 95% CI 0.0-0.62; p=0.044). Conclusions. We found significant differences between serum levels of LOXL2 in ILF group and CG, ILF group and COVID-19-associated LF. ROC analysis yielded the values of the optimal points of group separation by serum LOXL2 and periostin levels. This allows differential diagnosis of different pulmonary fibrosis.

легочный фиброзИЛФCOVID-19СА15-3периостинTGFBR3LOXL2pulmonary fibrosisIPFCOVID-19CA15-3periostinTGFBR3LOXL2Исследование было выполнено при поддержке гранта РНФ, договор № 22-25-00019 от 16.12.2021 г.The study was carried out with the support of a grant of Russian Science Foundation, agreement No. 22-25-00019 from 16 December 16, 2021.ReferencesАнаев Э.Х. Биомаркеры идиопатического легочного фиброза // Практическая пульмонология. 2016. №4. С. 24-30.Anaev E.H. Biomarkers of idiopathic pulmonary fibrosis // Practical Pulmonology. 2016; 4: 24-30.Ability of Periostin as a New Biomarker of Idiopathic Pulmonary Fibrosis / I. Okamoto [et al.] // MPeriostin. 2019: 79–87. DOI:10.1007/978-981-13-6657-4_9Ability of Periostin as a New Biomarker of Idiopathic Pulmonary Fibrosis / I. Okamoto [et al.] // MPeriostin. 2019: 79–87. DOI:10.1007/978-981-13-6657-4_9Blood Biomarkers in Idiopathic Pulmonary Fibrosis / Guiot J. [et al.] // Lung. 2017; 195(3): 273–280. DOI:10.1007/s00408-017-9993-5Blood Biomarkers in Idiopathic Pulmonary Fibrosis / Guiot J. [et al.] // Lung. 2017; 195(3): 273–280. DOI:10.1007/s00408-017-9993-5Combined detection of CA15-3, CEA, and SF in serum and tissue of canine mammary gland tumor patients / Fan Y. [et al.] // Sci Rep. 2021; 11(1): 6651. DOI: 10.1038/s41598-021-85029-4.Combined detection of CA15-3, CEA, and SF in serum and tissue of canine mammary gland tumor patients / Fan Y. [et al.] // Sci Rep. 2021; 11(1): 6651. DOI: 10.1038/s41598-021-85029-4.Developmental pathways in the pathogenesis of lung fibrosis / Chanda D. [et al.] // Mol. Aspects Med. 2018; 65:56-69. DOI:10.1016/j.mam.2018.08.004Developmental pathways in the pathogenesis of lung fibrosis / Chanda D. [et al.] // Mol. Aspects Med. 2018; 65:56-69. DOI:10.1016/j.mam.2018.08.004Existing and emerging biomarkers for disease progression in idiopathic pulmonary fibrosis / Inchingolo R. [et al.] // Expert Review of Respiratory Medicine. 2018: 1–13. DOI:10.1080/17476348.2019.1553620Existing and emerging biomarkers for disease progression in idiopathic pulmonary fibrosis / Inchingolo R. [et al.] // Expert Review of Respiratory Medicine. 2018: 1–13. DOI:10.1080/17476348.2019.1553620Genetic and non-genetic risk factors of idiopathic pulmonary fibrosis: A review / Zulkarneev S.R. [et al.] // Global Transl Med. 2022; 1(2): 107. DOI: 10.36922/gtm.v1i2.107Genetic and non-genetic risk factors of idiopathic pulmonary fibrosis: A review / Zulkarneev S.R. [et al.] // Global Transl Med. 2022; 1(2): 107. DOI: 10.36922/gtm.v1i2.107Global incidence and prevalence of idiopathic pulmonary fibrosis / Maher T.M. [et al.] // Respir Res. 2021; 22(1): 197. DOI: 10.1186/s12931-021-01791-z.Global incidence and prevalence of idiopathic pulmonary fibrosis / Maher T.M. [et al.] // Respir Res. 2021; 22(1): 197. DOI: 10.1186/s12931-021-01791-z.Idiopathic pulmonary fibrosis / Lederer D.J., Martinez F.J., Engl N. // J Med. 2018; 378:1811–1823. DOI:10.1056/NEJMra1705751Idiopathic pulmonary fibrosis / Lederer D.J., Martinez F.J., Engl N. // J Med. 2018; 378:1811–1823. DOI:10.1056/NEJMra1705751Inhibition of type III TGF-β receptor aggravates lung fibrotic process / Ahn J.Y. [et al.] // Biomed Pharmacother. 2010; 64(7): 472-6. DOI: 10.1016/j.biopha.2010.01.006.Inhibition of type III TGF-β receptor aggravates lung fibrotic process / Ahn J.Y. [et al.] // Biomed Pharmacother. 2010; 64(7): 472-6. DOI: 10.1016/j.biopha.2010.01.006.Linking LOXL2 to Cardiac Interstitial Fibrosis / Erasmus M. [et al.] // Int J Mol Sci. 2020. Vol. 21(16). Р. 5913. DOI:10.3390/ijms21165913Linking LOXL2 to Cardiac Interstitial Fibrosis / Erasmus M. [et al.] // Int J Mol Sci. 2020. Vol. 21(16). Р. 5913. DOI:10.3390/ijms21165913LOX/LOXL in pulmonary fibrosis: potential therapeutic targets / Chen L. [et al.] // Journal of Drug Targeting. 2018; 1–23. DOI:10.1080/1061186x.2018.1550649LOX/LOXL in pulmonary fibrosis: potential therapeutic targets / Chen L. [et al.] // Journal of Drug Targeting. 2018; 1–23. DOI:10.1080/1061186x.2018.1550649LOXL2—A new target in antifibrogenic therapy? / Puente А. [et al.] // Int J Mol Sci. 2019:20(7): 1634. DOI: 10.3390/ijms20071634.LOXL2—A new target in antifibrogenic therapy? / Puente А. [et al.] // Int J Mol Sci. 2019:20(7): 1634. DOI: 10.3390/ijms20071634.Periostin: A Potential Biomarker and Therapeutic Target in Pulmonary Diseases / Alzobaidi N. [et al.] // J Pharm Pharm Sci. 2022; 25:137-148. DOI: 10.18433/jpps32306.Periostin: A Potential Biomarker and Therapeutic Target in Pulmonary Diseases / Alzobaidi N. [et al.] // J Pharm Pharm Sci. 2022; 25:137-148. DOI: 10.18433/jpps32306.Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan / Li Y. [et al.] // China Histopathology. 2021; 78(4): 542–555. DOI:10.1111/his.14249.Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan / Li Y. [et al.] // China Histopathology. 2021; 78(4): 542–555. DOI:10.1111/his.14249.Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers / Khan T. [et al.] // Mol. Omics. 2021; 17(1): 43-58. DOI: 10.1039/d0mo00108b.Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers / Khan T. [et al.] // Mol. Omics. 2021; 17(1): 43-58. DOI: 10.1039/d0mo00108b.Serum CA 15-3 is increased in pulmonary fibrosis / Ricci A. [et al.] // Sarcoidosis Vasc Diffuse Lung Dis. 2009; 26(1): 54-63.Serum CA 15-3 is increased in pulmonary fibrosis / Ricci A. [et al.] // Sarcoidosis Vasc Diffuse Lung Dis. 2009; 26(1): 54-63.Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series / d'Alessandro M. [et al.] // Cancers (Basel). 2021; 13(3): 539. DOI: 10.3390/cancers13030539.Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series / d'Alessandro M. [et al.] // Cancers (Basel). 2021; 13(3): 539. DOI: 10.3390/cancers13030539.TGF-β receptors: In and beyond TGF-β signaling / Vander Ark A., Cao J., Li X. // Cellular Signalling. 2018; 52:112–120. DOI: 10.1016/j.cellsig.2018.09.002TGF-β receptors: In and beyond TGF-β signaling / Vander Ark A., Cao J., Li X. // Cellular Signalling. 2018; 52:112–120. DOI: 10.1016/j.cellsig.2018.09.002The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis / Ohta S. [et al.] // PLoS. One. 2017; 12(3): e0174547. DOI: 10.1371/journal.pone.0174547The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis / Ohta S. [et al.] // PLoS. One. 2017; 12(3): e0174547. DOI: 10.1371/journal.pone.0174547

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