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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2021-11-66-71</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-6290</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ГАСТРОЭНТЕРОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>GASTROENTEROLOGY</subject></subj-group></article-categories><title-group><article-title>Патогенетическая и диагностическая значимость мониторинга кишечной фракции белков, связывающих жирные кислоты, у детей с гастроинтестинальными формами пищевой аллергии</article-title><trans-title-group xml:lang="en"><trans-title>Analysis of the content of I-FABP in urine and blood serum in children with gastrointestinal food allergy</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2106-2572</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Приходченко</surname><given-names>Н. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Prikhodchenko</surname><given-names>N. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Приходченко Нелли Григорьевна - доктор медицинских наук, доцент Института педиатрии.</p><p>90002, Владивосток, проспект Острякова, д. 2</p></bio><bio xml:lang="en"><p>Nelli G. Prikhodchenko, Dr. Sci. (Med.), Associate Professor, Institute of Pediatrics.</p><p>2, Ostryakov Ave., Vladivostok, 690002</p></bio><email xlink:type="simple">prikhodchenko_n@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2668-8483</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шуматова</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shumatova</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шуматова Татьяна Александровна - доктор медицинских наук, профессор, директор Института педиатрии.</p><p>690002, Владивосток, проспект Острякова, д. 2</p></bio><bio xml:lang="en"><p>Tatyana A. Shumatova, Dr. Sci. (Med.), Professor, Director of Institute of Pediatrics.</p><p>2, Ostryakov Ave., Vladivostok, 690002</p></bio><email xlink:type="simple">shumatov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6926-3341</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ни</surname><given-names>А.</given-names></name><name name-style="western" xml:lang="en"><surname>Nee</surname><given-names>A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ни Антонина - доктор медицинских наук, профессор Института педиатрии.</p><p>690002, Владивосток, проспект Острякова, д. 2</p></bio><bio xml:lang="en"><p>Nee, Dr. Sci. (Med.), Рrofessor of Institute of Pediatrics.</p><p>2, Ostryakov Ave., Vladivostok, 690002</p></bio><email xlink:type="simple">neeant56@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0748-5819</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зернова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zernova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Зернова Екатерина Сергеевна - кандидат медицинских наук, ассистент Института педиатрии.</p><p>690002, Владивосток, проспект Острякова, д. 2</p></bio><bio xml:lang="en"><p>Ekaterina S. Zernova, Cand. Sci. (Med.), Assistant of the Institute of Pediatrics.</p><p>2, Ostryakov Ave., Vladivostok, 690002</p></bio><email xlink:type="simple">kate-zernova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Тихоокеанский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pasific State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>08</day><month>08</month><year>2021</year></pub-date><volume>0</volume><issue>11</issue><fpage>66</fpage><lpage>71</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Приходченко Н.Г., Шуматова Т.А., Ни А., Зернова Е.С., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Приходченко Н.Г., Шуматова Т.А., Ни А., Зернова Е.С.</copyright-holder><copyright-holder xml:lang="en">Prikhodchenko N.G., Shumatova T.A., Nee A., Zernova E.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/6290">https://www.med-sovet.pro/jour/article/view/6290</self-uri><abstract><sec><title>Введение</title><p>Введение. Белок-индуцированная энтеропатия является частым проявлением гастроинтестинальной пищевой аллергии у детей раннего возраста. Для своевременной постановки диагноза и профилактики обострений особенно актуален поиск неинвазивных методов диагностики.</p><p>Цель данного исследования – определить сывороточный и уринальный уровень кишечной фракции белков, связывающих жирные кислоты, у детей с белок- индуцированной энтеропатией и оценить их клиническую и диагностическую значимость.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Было обследовано 36 детей с белок- индуцированной энтеропатией в возрасте от 1,5 мес. до 1 года и 20 здоровых детей (контрольная группа). Для дифференциальной диагностики с врожденными заболеваниями желудочно-кишечного тракта всем пациентам была проведена эзофагогастроеюноскопия с морфологическим исследованием биоптатов. Для оценки клинических симптомов использована шкала The Cow’s Milk-related Symptom Score (CoMMiS). Всем детям в сыворотке крови и моче методом энзимсвязанного иммуносорбентного анализа определяли кишечную фракцию белка, связывающего жирные кислоты.</p></sec><sec><title>Результаты</title><p>Результаты. Выявлено повышение белка в крови 125,20 ± 23,79 пг/мл, в моче 0,164 ± 0,031 пкг/мл по сравнению с группой контроля (19,21 ± 4,94 пг/мл, 0,039 ± 4,62 пкг/мл соответственно, p &lt; 0,05). Обнаружены прямые сильные связи между степенью морфологических изменений, клинической выраженностью гастроинтестинальных проявлений и концентрацией белка, связывающего жирные кислоты, в сыворотке и в моче.</p></sec><sec><title>Обсуждение</title><p>Обсуждение. Повреждение эпителиального барьера, обеспечивающего повышенное проникновение интактных пищевых аллергенов, играет ключевую роль в аллергической сенсибилизации, а в большинстве случаев является и первым патогенетическим звеном аллергического воспаления. Статистически значимое (p &lt; 0,05) повышение I-FABP во всех изучаемых биологических жидкостях у детей с белок-индуцированной энтеропатией тесно коррелирует с морфологическими изменениями СОТК, обнаруженными нами при гистологическом исследовании, а также с клиническими симптомами поражения желудочно-кишечного тракта, оцененными нами при помощи шкалы COMISS, что подтверждает его высокую информационную ценность для косвенной оценки состояния кишечного барьера.</p></sec><sec><title>Выводы</title><p>Выводы. Определение сывороточного и уринального уровня I-FABP у детей с белок-индуцированной энтеропатией может служить в качестве объективного критерия при оценке состояния кишечного барьера, исследование данного биомаркера в динамике может служить для контроля над течением заболевания. Его высокая чувствительность и специфичность определения в моче перспективна для использования в педиатрической практике.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Abstract Introduction</title><p>Abstract Introduction. Protein-induced enteropathy is one of the common manifestations of gastrointestinal food allergy in young children. The search of non-invasive methods for intestine estimation is especially relevant for early diagnosis and timely prevention of exacerbation.</p><p>The aim of the study was to determine the serum and urinal levels of the intestinal fraction of the protein binding fatty acids in children with protein-induced enteropathy and to evaluate their clinical and diagnostic significance.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. It was examined 36 children with protein-induced enteropathy aged 1.5 months to 1 year and 20 healthy children (control group). All patients underwent esophagogastroenteroscopy with morphological examination of biopsy specimens for differential diagnosis with congenital gastrointestinal diseases. The Cow’s Milk-related Symptom Score (CoMMiS) was used to evaluate clinical symptoms. The intestinal fraction of a fatty acid binding protein was determined for all children in blood serum, urine by enzyme- linked immunosorbent analysis.</p></sec><sec><title>Results</title><p>Results. It was found the increase its serum level (125.20 ± 23.79 pg / ml), and urinal level (0.164 ± 0.031 pkg / ml) compared with the control group (19.21 ± 4.94 pg / ml, 00.039 ± 4.62 pkg / ml, respectively, p &lt; 0.05). There were found direct strong correlations between the severity of gastrointestinal manifestations and its serum and urine level (p &lt; 0.05).</p></sec><sec><title>Discussion</title><p>Discussion. Epithelial barrier damage provides an increased penetration of intact food allergens. It plays a key role in allergic sensitization, and it is the first pathogenetic link of allergic inflammation in most cases. A statistically significant I-FABP increased level in all studied biological fluids correlates with morphological changes in the children with protein-induced enteropathy, as well as with clinical symptoms of gastrointestinal tract lesions. That confirms its high informational value for an indirect assessment of the state of the intestinal barrier.</p></sec><sec><title>Conclusions</title><p>Conclusions. Thus, an increase in serum and urinal I-FABP levels in children with protein-induced enteropathy confirms the clinical and diagnostic significance of determining this biomarker in all biological fluids. Its high sensitivity and specificity of determination in urine are promising for use in pediatric practice.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>кишечная фракция белка</kwd><kwd>связывающего жирные кислоты (I-FABP)</kwd><kwd>кишечный барьер</kwd><kwd>пищевая аллергия</kwd><kwd>дети</kwd></kwd-group><kwd-group xml:lang="en"><kwd>intestinal fraction of fatty acid binding protein (I-FABP)</kwd><kwd>intestinal barrier</kwd><kwd>food allergy</kwd><kwd>children</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Макарова С.Г., Намазова- Баранова Л.С., Вишнева Е.А., Геворкян А.К., Алексеева А.А., Петровская М.И. Актуальные вопросы диагностики пищевой аллергии в педиатрической практике. Вестник Российской академии медицинских наук. 2015;(1):41–46. Режим доступа: https://cyberleninka.ru/article/n/aktualnye-voprosy-diagnostiki-pischevoyallergii-v-pediatricheskoy-praktike.</mixed-citation><mixed-citation xml:lang="en">Makarova S.G., Namazova- Baranova L.S., Vishneva E.A., Gevorkyan A.K., Alekseeva A.A., Petrovskaya M.I. Actual issues of the diagnosis of food allergies in pediatric practice. Vestnik Rossiiskoi Akademii meditsinskikh nauk = Annals of the Russian Academy of Medical Science. 2015;(1):41–46. (In Russ.) Available at: https://cyberleninka.ru/article/n/aktualnye-voprosydiagnostiki-pischevoy-allergii-v-pediatricheskoy-praktike.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Dhondalay G.K., Rael E., Acharya S., Zhang W., Sampath V., Galli S.J. et al. Food allergy and omics. J Allergy Clin Immunol. 2018;1:20–29. https://doi.org/10.1016/j.jaci.2017.11.007.</mixed-citation><mixed-citation xml:lang="en">Dhondalay G.K., Rael E., Acharya S., Zhang W., Sampath V., Galli S.J. et al. Food allergy and omics. J Allergy Clin Immunol. 2018;1:20–29. https://doi.org/10.1016/j.jaci.2017.11.007.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Макарова С.Г., Намазова- Баранова Л.С., Вишнёва Е.А., Ерешко О.А., Гордеева И.Г. Гастроинтестинальная пищевая аллергия у детей. Вопросы современной педиатрии. 2017;16(3):202–212. https://doi.org/10.15690/vsp.v16i3.1730.</mixed-citation><mixed-citation xml:lang="en">Makarova S.G., Namazova- Baranova L.S., Vishneva E.A., Ereshko O.A., Gordeeva I.G. Gastrointestinal food allergy in children. Voprosy sovremennoi pediatrii = Current Pediatrics. 2017;16(3):202–212. (In Russ.)  https://doi.org/10.15690/vsp.v16i3.1730.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Knol E.F., de Jong N.W., Ulfman L.H., Tiemessen M.M. Management of Cow’s Milk Allergy from an Immunological Perspective: What Are the Options? Nutrients. 2019;11(11):2734. https://doi.org/10.3390/nu11112734.</mixed-citation><mixed-citation xml:lang="en">Knol E.F., de Jong N.W., Ulfman L.H., Tiemessen M.M. Management of Cow’s Milk Allergy from an Immunological Perspective: What Are the Options? Nutrients. 2019;11(11):2734. https://doi.org/10.3390/nu11112734.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Shah N., Foong R.X., Borrelli O., Volonaki E., Dziubak R., Meyer R. et al. Histological findings in infants with Gastrointestinal food allergy are associated with specific gastrointestinal symptoms; retrospective review from a tertiary centre. BMC Clin Pathol. 2015;15:12. https://doi.org/10.1186/s12907-015-0012-6.</mixed-citation><mixed-citation xml:lang="en">Shah N., Foong R.X., Borrelli O., Volonaki E., Dziubak R., Meyer R. et al. Histological findings in infants with Gastrointestinal food allergy are associated with specific gastrointestinal symptoms; retrospective review from a tertiary centre. BMC Clin Pathol. 2015;15:12. https://doi.org/10.1186/s12907-015-0012-6.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Wells J.M., Brummer R.J., Derrien M., MacDonald T.T., Troost F., Cani P.D. et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G171–G193. https://doi.org/10.1152/ajpgi.00048.2015.</mixed-citation><mixed-citation xml:lang="en">Wells J.M., Brummer R.J., Derrien M., MacDonald T.T., Troost F., Cani P.D. et al. Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G171–G193.  https://doi.org/10.1152/ajpgi.00048.2015.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Vancamelbeke M., Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9): 821–834. https://doi.org/10.1080/17474124.2017.1343143.</mixed-citation><mixed-citation xml:lang="en">Vancamelbeke M., Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9): 821–834. https://doi.org/10.1080/17474124.2017.1343143.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Шуматова Т.А., Шишацкая С.Н., Зернова Е.С., Ни А.Н., Катенкова Э.Ю., Приходченко Н.Г. и др. Совершенствование диагностики аллергии к белкам коровьего молока у детей грудного возраста. Тихоокеанский медицинский журнал. 2016;61(4):19–21. https://doi.org/10.17238/PmJ1609-1175.2016.4.19-22.</mixed-citation><mixed-citation xml:lang="en">Shumatova T.A., Shishatskaya S.N., Zernova E.S., Ni A.N., Katenkova E.Yu., Prikhodchenko N.G. et al. Improving the diagnosis of allergy to cow’s milk proteins in infants. Tikhookeanskii meditsinskii zhurnal = Pacific Medical Journal. 2016; 61(4):19–21. (In Russ.) https://doi.org/10.17238/PmJ1609-1175.2016.4.19–22.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Thumser A.E., Plant N.J., Moore J.B. Fatty acid binding proteins: Tissue- specific functions in health and disease. Curr Opin Clin Nutr Metab Care. 2014;17(2):124–129. https://doi.org/10.1097/MCO.0000000000000031.</mixed-citation><mixed-citation xml:lang="en">Thumser A.E., Plant N.J., Moore J.B. Fatty acid binding proteins: Tissue- specific functions in health and disease. Curr Opin Clin Nutr Metab Care. 2014;17(2):124–129. https://doi.org/10.1097/MCO.0000000000000031.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Gajda A.M., Storch J. Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot Essent Fatty Acids. 2015;93:9–16. https://doi.org/10.1016/j.plefa.2014.10.001.</mixed-citation><mixed-citation xml:lang="en">Gajda A.M., Storch J. Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot Essent Fatty Acids. 2015;93:9–16. https://doi.org/10.1016/j.plefa.2014.10.001.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Huang- Fu C.R., Li Р., Tian Y.F. Clinical significance of serum intestinal fatty acid-binding protein in full-term infants with necrotizing enterocolitis. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(11):1125–1128. Available at: https://pubmed.ncbi.nlm.nih.gov/25406557.</mixed-citation><mixed-citation xml:lang="en">Huang- Fu C.R., Li Р., Tian Y.F. Clinical significance of serum intestinal fatty acid-binding protein in full-term infants with necrotizing enterocolitis. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(11):1125–1128. Available at: https://pubmed.ncbi.nlm.nih.gov/25406557.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Криворучко И.А., Бойко В.В., Гончарова Н.Н., Тарабан И.А., Арсеньев А.В., Иванова Ю.В. и др. Оценка биомаркера кишечного барьера I-FABP и тяжести состояния пациентов при остром панкреатите. Новости хирургии. 2019;27(6):640–649. Режим доступа: https://cyberleninka.ru/article/n/otsenka-biomarkera-kishechnogo-bariera-i-fabp-i-tyazhesti-sostoyaniya-patsientov-pri-ostrom-pankreatite/viewer.</mixed-citation><mixed-citation xml:lang="en">Krivoruchko I.A., Boyko V.V., Goncharova N.N., Taraban I.A., Arsenyev A.V., Ivanova Yu.V. et al. Evaluation of the biomarker of the intestinal barrier I-FABP and the severity of patients with acute pancreatitis. Novosti hirurgii. 2019;27(6):640–649. (In Russ.) Available at: https://cyberleninka.ru/article/n/otsenka-biomarkera-kishechnogo-bariera-i-fabp-i-tyazhesti-sostoyaniya-patsientov-pri-ostrom- pankreatite/viewer.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Güzel M., Sözüer E.M., Salt Ö., İkizceli İ., Akdur O., Yazıcı C. Value of the serum I-FABP level for diagnosing acute mesenteric ischemia. Surg Today. 2014;44:2072–2076. https://doi.org/10.1007/s00595-013-0810-3.</mixed-citation><mixed-citation xml:lang="en">Güzel M., Sözüer E.M., Salt Ö., İkizceli İ., Akdur O., Yazıcı C. Value of the serum I-FABP level for diagnosing acute mesenteric ischemia. Surg Today. 2014;44:2072–2076. https://doi.org/10.1007/s00595-013-0810-3.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Coufal S., Kokesova A., Tlaskalova- Hogenova H., Frybova B., Snajdauf J., Rygl M. et al. Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease. J Immunol Res. 2020;2020:3074313. https://doi.org/10.1155/2020/3074313.</mixed-citation><mixed-citation xml:lang="en">Coufal S., Kokesova A., Tlaskalova- Hogenova H., Frybova B., Snajdauf J., Rygl M. et al. Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease. J Immunol Res. 2020;2020:3074313. https://doi.org/10.1155/2020/3074313.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
