Pediatrician (St. Petersburg)Pediatrician (St. Petersburg)2079-78502587-6252Eco-Vector1914710.17816/PED1055-12Research ArticleGastrointestinal risk factors for anemia in children with celiac diseaseShapovalovaNatalia S.<p>Junior Researcher, Research Center</p>natasunday@mail.ruNovikovaValeriya P.<p>MD, PhD, Dr Med Sci, Professor, Head, Laboratory of Medical and Social Problems in Pediatrics</p>novikova-vp@mail.ruRevnovaMaria O.<p>MD, PhD, Dr Med Sci, Professor, Head of Outpatient Pediatrics Department named after Academician A.F. Tour</p>revnoff@mail.ruGurinaOlga P.<p>MD, PhD, Senior Researcher, Research Center</p>ol.gurina@yandex.ruDementievaElena A.<p>Junior Researcher, Research Center</p>zorra2@yandex.ruKlikunovaKsenia A.<p>PhD, Associate Professor, Department of Medical Physics</p>kliksa@gmail.comSt. Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation2812201910551228012020Copyright © 2020, Shapovalova N.S., Novikova V.P., Revnova M.O., Gurina O.P., Dementieva E.A., Klikunova K.A.2020<p>With oral intake, iron absorption in patients with celiac disease (CD) is reduced due to the decreased absorption surface of the atrophic small intestine mucous membrane. Besides, there are additional risk factors for anemia whose mechanisms are unclear.<em>The aim</em>of this study was to evaluate gastrointestinal risk factors for anemia in children.</p>
<p><strong>Materialsand methods.</strong>The first group consisted of 58 children with newly diagnosed CD who did not adhere to the gluten-free diet(GFD). The second group included 49 children with CD who hasnt been adhering to the GFD. The third group included 69children with chronic gastritis (CG) without CD. In addition to the standard examination, which includes the determination of antibodies to tissue transglutaminase and histological examination of the duodenum mucous membrane, a histological evaluation of the gastric mucosa, determination of pepsinogen 1 and 2 and their ratio, antibodies to Castles intrinsic factor were performed.</p>
<p><strong>Results.</strong>The mean level of hemoglobin in the group 1<sub>114,71</sub>120,10<sub>125,50</sub>g/l, in the group 2<sub>124,37</sub>128,74<sub>133,10</sub>g/l, in the group 3<sub>130,12</sub>133,78<sub>137,43</sub>g/l (<em>p</em><sub>1,2</sub>=0.013;<em>p</em><sub>1,3</sub>=0,000;<em>p</em><sub>2,3</sub>=0.083). A correlation analysis of the hemoglobin level and morphological parameters of the duodenal mucosa among the studied patients revealed an inverse moderate correlation between the hemoglobin level and the degree of the small intestinal atrophy according to Marsh<em>r</em>=0.331,<em>p</em>=0,000, crypt depth<em>r</em>=0,439,<em>p</em>=0,000, and a moderate direct with the ratio of villi:crypt<em>r</em>=0.417,<em>p</em>=0.000, with the height of the villi<em>r</em>=0.366,<em>p</em>=0,000. Additionally, a moderate direct correlation between the level of hemoglobin and the number of parietal cells was found to be<em>r</em>=0.354,<em>p</em>=0.037. In group 1, a significant inverse correlation between the level of hemoglobin and the level of antibodies to Castles factor<em>r</em>=0.529,<em>p</em>=0.006, was obtained for the level of antibodies in the Castles factor.</p>
<p><strong>Conclusion.</strong>Autoimmune gastritis may be an additional risk factor in combination with malabsorption, as a possible cause of anemia in children with CD.</p>anemiahemoglobinceliac diseaseantibodies to Castle intrinsic factorchildrenанемиягемоглобинцелиакияантитела к внутреннему фактору Кастладети<h2>INTRODUCTION</h2>
<p>The onset of celiac disease can manifest as anemia; therefore, pediatric patients with chronic iron deficiency anemia (IDA) areat risk for celiac disease and should be screened [7].According to the literature, the incidence of anemia among celiacdisease patients who do not receive a gluten-free diet (GFD) ranges from 12% to 69% [9]. However, the mechanism of therelationship between these two diseases remains unclear. A 2017 studybyRajalahtiandMkishowed that GFD for 1year resulted in the resolution of anemia in 92% ofpediatric patients with celiac disease. However, their hemoglobin levels were even lower aftercure than in the control group of children without celiacdisease [22].</p>
<p>Iron is a critical trace element that deficiency canbe noted both with a typical manifestation of celiac diseaseand in the absence of diarrhea and weight loss [4].It is obvious that with oral administration, iron absorption inceliac disease is reduced because of decreased absorption surface ofthe atrophic mucous membrane of the small intestine, which isthe main factor in anemia. In addition, erosive processes andneoplasms of the gastrointestinal tract in the complicated course ofceliac disease can become an additional etiological factor in anemiaduring the development of bleeding [8, 17, 19]. Also, withceliac disease, there may be a disorder of expression ofproteins significant for iron absorption, namely, divalent metal transporter-1 (DMT-1),ferroportin, hephaestin, and ferritin receptor mRNA. Thus, a decrease inserum iron and an increase in the expression of ferritinare registered both in patients with celiac disease and inthe control group with iron deficiency [5], and the expressionof DMT-1 and ferroportin is increased in patients with celiacdisease with and without iron deficiency [20]. These factors maybe significant in the pathogenesis of celiac disease itself. Itwas revealed that gluten can penetrate the body using transferrinreceptors on enterocytes, in which expression is increased with irondeficiency [10]. Celiac disease is an autoimmune disease that ischaracterized by chronic inflammation of the mucous membrane of thesmall intestine in the active phase. Acute phase cytokines andproteins play an important role in the pathogenesis of anemiaof the chronic disease. Changes in iron metabolism through hepcidinand ferritin molecules can contribute to both IDA and chronicinflammation anemia additionally.</p>
<p>Anemia associated with autoimmune gastritis (AG) has notbeen described for celiac disease. At the same time, thereare few reports of AG in patients with celiac disease[1, 2].</p>
<p><em>This study aimed</em>to evaluate gastrointestinal risk factors foranemia in children.</p>
<h2>MATERIALS AND METHODS</h2>
<p>A total of 176 children from3 to 16 years old were examined. Group 1 consistedof 58 pediatric patients with newly diagnosed celiac disease, whowere not on a GFD. Group 2 included 49 patientswith celiac disease on GFD. For comparison, Group 3 included69 pediatric patients with chronic gastritis without celiac disease.</p>
<p>Allpatients were examined according to a single protocol. The diagnosisof celiac disease was established based on the federal clinicalguidelines for the medical care of children with celiac disease of the Ministry of Health of the Russian Federation andthe Union of Pediatricians of 2015 [14] and the guidelines for celiac disease of theEuropean Society for PaediatricGastroenterology Hepatology and Nutritionof 2012 [15]. The analysisof clinical and anamnestic data was performed, and the presenceof positive specific antibodies (IgG and IgA) against deamidated gliadinpeptides and tissue transglutaminase-2 was taken into account. Human leukocyte antigen genotyping wasperformed to detect celiac disease-associated<em>DQ2</em>and<em>DQ8</em>genes. Allpatients underwent a morphometric examination of the duodenal mucous membrane(DMM). Detection of atrophy to a degree not less thanMarsh 3a proved the presence of celiac disease. Also, based on all the above conciliation documents [15], the diagnosis of celiac diseasewas ruled out in patients of the comparison group. Thediagnosis of chronic gastritis was verified morphologically for all studyparticipants. Biopsy samples of the mucous membrane of the fundusand antrum of the stomach were obtained with esophagogastroduodenoscopy performedusing an Evis ExeraII OLYMPUS apparatus of the HGi180 type (Japan) using a standard technique. The endoscopic andhistological evaluation of the gastric mucosa was performed according tothe Sydney system. Determination of the levels of hemoglobin(g/L), red blood cells (10<sup>12</sup>L), mean corpuscular volume (MCV;fl), mean corpuscular hemoglobin (MCH; units), andmean cell hemoglobin concentration (MCHC; pg) was included inthe general clinical examination. Antibodies (IgG) to Castles intrinsicfactor were determined in the blood plasma by enzyme-linked immunosorbentassay on a standard photometer using the kits manufactured by EUROIMMUN Medizinische Labordiagnostica AG, Germany, from 140children. According to the instructions, the negative result was 020au/mL, and a positive result is 20 au/mL.</p>
<p>Statistical analysis was performedusing the IBM SPSS Statistics 23. The average antibody levelwas calculated with a 95% confidence interval (CI), indicating theupper and lower limits, median, and mean square deviation. For comparison of means, the Students<em>t</em>-test was usedfor independent samples (two-tailed significance level,<em>p</em> 0.05),as well as MannWhitney<em>U</em>-test. The Livin dispersion equalitycriterion, KolmogorovSmirnov test, and ShapiroWilk test were taken into account. To analyze endoscopic and morphological studies ingroups, the Fishers exact test was used (significance<em>p</em>0.05).</p>
<h2>RESULTS</h2>
<p>Anemia in Group 1 was diagnosed in 18.9 cases, while in group 2, it was registeredin 2.0% and did not occur in Group 3 (0.0%;<em>p</em><sub>1,2</sub>= 0.017;<em>p</em><sub>1,3</sub>= 0.001;<em>p</em><sub>2,3</sub>= 0.261).Among patients with anemia, hypochromic and microcytic anemia was noted, mainly of mild severity, with an average hemoglobin level of97.88 8.6 g/L. Only one patient in Group 1 had moderateanemia with a hemoglobin level of 74 g/L. This childhad atypical celiac disease with a single complaint of recurrentIDA. The average level of red blood cells among anemiapatients was 3.66 0.52 10<sup>12</sup>L; MCV was77.63 1.09 fl; MCH was 26.50 0.77units; MCHC was 32.00 0.89 pg.</p>
<p>The average hemoglobinlevel was the lowest in Group 1 with statistically significantdifferences compared with that in Groups 2 and 3 andthe highest in Group 3 with a statistically significant differencerelative to Groups 1 and 2. The data are presentedin Table 1.</p>
<p></p>
<p><em>Table1/ </em><em>Таблица</em><em> 1</em></p>
<p>The mean level of hemoglobin in groups</p>
<p>Средний уровень гемоглобина в группах</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Groups/ Группы</p>
</td>
<td>
<p>Hemoglobin g/l* / Гемоглобин г/л*</p>
</td>
<td>
<p>Standard deviation/ Ср. кв. отклонение</p>
</td>
<td>
<p><em>t</em>**Students<em>t</em>-test/ Коэффициент Стьюдента</p>
</td>
</tr>
<tr>
<td>
<p>Group1 / Группа 1</p>
</td>
<td>
<p><sub>114.71</sub>120.10<sub>125.50</sub></p>
</td>
<td>
<p>16.64</p>
</td>
<td rowspan="3">
<p><em>p</em><sub>1.2</sub>= 0.013</p>
<p><em>p</em><sub>1.3</sub>= 0.000</p>
<p><em>p</em><sub>2.3</sub>= 0.083</p>
</td>
</tr>
<tr>
<td>
<p>Group2 / Группа 2</p>
</td>
<td>
<p><sub>124.37</sub>128.74<sub>133.10</sub></p>
</td>
<td>
<p>14.01</p>
</td>
</tr>
<tr>
<td>
<p>Group3 / Группа 3</p>
</td>
<td>
<p><sub>130.12</sub>133.78<sub>137.43</sub></p>
</td>
<td>
<p>10.80</p>
</td>
</tr>
<tr>
<td colspan="4">
<p><em>Note.</em>The hemoglobin level is represented in mean value with upper and lower limits, a standard deviation with a 95% confidence interval. Levenes Test for equality of variances and Students<em>t</em>-test for paired comparison were used.</p>
<p><em>Примечание.</em>*Уровень гемоглобина представлен средним значением с указанием верхней и нижней границ, среднеквадратичного отклонения с 95 % доверительным интервалом. **Равенство дисперсий проверено критерием Ливиня, при парном сравнении использовался критерий Стьюдента.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>The average erythrocyte count was significantly different inall groups and was lower in Group 1, with astatistically significant difference related to Groups2 and 3. Thedata are presented in Table 2.</p>
<p></p>
<p><em>Table2/ </em><em>Таблица</em><em> 2</em></p>
<p>The mean level of erythrocytes in groups</p>
<p>Средний уровень эритроцитов в группах</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Groups/ Группы</p>
</td>
<td>
<p>Erythrocytes10<sup>12</sup>l* / Эритроциты 10<sup>12</sup>л*</p>
</td>
<td>
<p>Standard deviation/ Ср. кв. отклонение</p>
</td>
<td>
<p>MannWhitney<em>U</em>-test/<em>U</em>-критерий** Манна Уитни</p>
</td>
</tr>
<tr>
<td>
<p>Group1 / Группа 1</p>
</td>
<td>
<p><sub>3.97</sub>4.16<sub>4.35</sub></p>
</td>
<td>
<p>0.59</p>
</td>
<td rowspan="3">
<p><em><u>р</u></em><sub>1.2</sub>= 0.002</p>
<p><em>р</em><sub>1.3</sub>= 0.000</p>
<p><em>р</em><sub>2.3</sub>= 0.016</p>
</td>
</tr>
<tr>
<td>
<p>Group2 / Группа 2</p>
</td>
<td>
<p><sub>3.38</sub>4.54<sub>4.70</sub></p>
</td>
<td>
<p>0.50</p>
</td>
</tr>
<tr>
<td>
<p>Group3 / Группа 3</p>
</td>
<td>
<p><sub>4.67</sub>4.82<sub>4.97</sub></p>
</td>
<td>
<p>0.36</p>
</td>
</tr>
<tr>
<td colspan="4">
<p><em>Note.</em>*The hemoglobin levelis represented in maen value with upper and lower limits,a standard deviation with a 95% confidence interval. **Levenes Test for equality of variances and MannWhitney<em>U</em>-test for paired comparison were used.</p>
<p><em>Примечание.</em>*Уровень гемоглобина представлен средним значением с указанием верхней и нижней границ, среднеквадратичного отклонения с 95% доверительным интервалом. **Равенство дисперсий проверено критерием Ливиня, при парном сравнении использовался критерий Манна Уитни.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>The average erythrocyte MCV levelsdid not differ statistically significantly; they were 83.60 0.90,83.95 1.70, and 85.13 1.73 fl in Groups 1,2, and3, respectively (<em>p</em><sub>1,2</sub>= 0.848;<em>p</em><sub>1,3</sub>= 0.180;<em>p</em><sub>2,3</sub>= 0.416).The average level of MCH did not differ in thegroups, as it was 28.24 0.61 units in Group1, 28.51 0.58units in Group 2, and 28.05 0.45 units in Group 3 (<em>p</em><sub>1,2</sub>= 0.864;<em>p</em><sub>1,3</sub>= 0.663;<em>p</em><sub>2,3</sub>= 0.835). The average level of MCHC differed statistically significantly forGroups 1 and 3; it was 32.51 0.44unitsin Group1, 33.31 0.57 pg in Group 2,and 33.56 0.53pg inGroup 3 (<em>p</em><sub>1,2</sub>= 0.051;<em>p</em><sub>1,3</sub>= 0.007;<em>p</em><sub>2,3</sub>=0.6). Correlation analysis of the hemoglobin level and morphologicalindicators of DMM among the patients studied revealed an inversemoderate correlation between the hemoglobin level and DMM atrophy degreeaccording to Marsh, the crypt depth, and a moderate direct correlation with the ratio ofthe villus: DMM crypts and DMM villi height. The dataare presented in Table 3.</p>
<p></p>
<p><em>Table3/ </em><em>Таблица</em><em> 3</em></p>
<p>Analysis of the linear correlation of hemoglobin level and morphological parameters of the duodenal mucosa</p>
<p>Анализ линейной корреляционной связи уровня гемоглобина и морфологических показателей слизистой оболочки двенадцатиперстной кишки</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Parameter/ Показатель</p>
</td>
<td>
<p>Pearsons coefficient/Коэффициент Пирсона</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
<td>
<p>Spearmans coefficient/ Коэффициент Спирмена</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
</tr>
<tr>
<td>
<p>The Marsh degree of duodenal mucosa atrophy/Степень атрофии слизистой оболочки двенадцатиперстной кишки поМarsh</p>
</td>
<td>
<p></p>
</td>
<td>
<p></p>
</td>
<td>
<p>0.331</p>
</td>
<td>
<p>0.000</p>
</td>
</tr>
<tr>
<td>
<p>Villus height/ Высота ворсин</p>
</td>
<td>
<p>0.354</p>
</td>
<td>
<p>0.000</p>
</td>
<td>
<p>0.366</p>
</td>
<td>
<p>0.000</p>
</td>
</tr>
<tr>
<td>
<p>Crypt depth/ Глубина крипт</p>
</td>
<td>
<p>0.380</p>
</td>
<td>
<p>0.000</p>
</td>
<td>
<p>0.439</p>
</td>
<td>
<p>0.000</p>
</td>
</tr>
<tr>
<td>
<p>Ratio villus:crypt/ Отношение ворсина: крипта</p>
</td>
<td>
<p>0.413</p>
</td>
<td>
<p>0.000</p>
</td>
<td>
<p>0.417</p>
</td>
<td>
<p>0.000</p>
</td>
</tr>
<tr>
<td colspan="5">
<p><em>Note.</em>Pearsons linear coefficient Spearmans rank correlation coefficient wereused.<sup>*</sup><em>р</em>bilateral significance.The values of the modulusof the correlation coefficient and Linear quality characteristic: |<em>r</em>| 0,3weak, 0,3 |<em>r</em>| 0,5moderate, 0,5 |<em>r</em>| 0,7significant, 0,7 |<em>r</em>| 0,9strong, 0,9 |<em>r</em>| 1very strong.</p>
<p><em>Примечание.</em>Использованы выборочный коэффициент Пирсона иранговый коэффициент Спирмена.<sup>*</sup><em>р</em> значимость двусторонняя.<em></em>Значения модуля коэффициента корреляции икачественная характеристика линейной связи. |<em>r</em>| 0,3 слабая, 0,3 |<em>r</em>| 0,5 умеренная, 0,5 |<em>r</em>| 0,7 значительная, 0,7 |<em>r</em>| 0,9 сильная, 0,9 |<em>r</em>| 1 очень сильная.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>When analyzing the linear correlation betweenthe hemoglobin level and gastric mucosa indices, a moderate directrelationship was found between the level of hemoglobin and thenumber of parietal cells in the mucous membrane of thegastric fundus. The data are presented in Table 4.</p>
<p></p>
<p><em>Table4/ </em><em>Таблица</em><em> 4</em></p>
<p>Analysis of the linear correlation of hemoglobin level and indices of the gastric mucosa</p>
<p>Анализ линейной корреляционной связи уровня гемоглобина и показателей слизистой оболочки тела желудка</p>
<table>
<thead>
<tr>
<td>
<p>Parameter/ Показатель</p>
</td>
<td>
<p>Pearsons coefficient/Коэффициент Пирсона</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
<td>
<p>Spearmans coefficient/ Коэффициент Спирмена</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
</tr>
</thead>
<tbody>
<tr>
<td colspan="5">
<p>Parameters of thegastric fundic mucous membrane/ Показатели слизистой оболочки дна желудка</p>
</td>
</tr>
<tr>
<td>
<p>The thickness of the gastric mucosa/ Толщина слизистой оболочки желудка</p>
</td>
<td>
<p>0.089</p>
</td>
<td>
<p>0.543</p>
</td>
<td>
<p>0.091</p>
</td>
<td>
<p>0.583</p>
</td>
</tr>
<tr>
<td>
<p>The depth of gastric pits/ Глубина ямок</p>
</td>
<td>
<p>0.112</p>
</td>
<td>
<p>0.492</p>
</td>
<td>
<p>0.174</p>
</td>
<td>
<p>0.284</p>
</td>
</tr>
<tr>
<td>
<p>The glands length/ Длина желез</p>
</td>
<td>
<p>0.197</p>
</td>
<td>
<p>0.222</p>
</td>
<td>
<p>0.159</p>
</td>
<td>
<p>0.328</p>
</td>
</tr>
<tr>
<td>
<p>The height of the integumentary epithelium/ Высота покровного эпителия</p>
</td>
<td>
<p>0.230</p>
</td>
<td>
<p>0.154</p>
</td>
<td>
<p>0.201</p>
</td>
<td>
<p>0.214</p>
</td>
</tr>
<tr>
<td>
<p>The height of glandular epithelium/ Высота железистого эпителия</p>
</td>
<td>
<p>0.101</p>
</td>
<td>
<p>0.535</p>
</td>
<td>
<p>0.141</p>
</td>
<td>
<p>0.385</p>
</td>
</tr>
<tr>
<td>
<p>The number of parietal cells/ Число париетальных клеток</p>
</td>
<td>
<p>0.304</p>
</td>
<td>
<p>0.056</p>
</td>
<td>
<p>0.281</p>
</td>
<td>
<p>0.079</p>
</td>
</tr>
<tr>
<td colspan="5">
<p>Parameters of thegastric fundic mucous membrane/ Показатели слизистой оболочки дна желудка</p>
</td>
</tr>
<tr>
<td>
<p>The thickness of the gastric mucosa/ Толщина слизистой оболочки желудка</p>
</td>
<td>
<p>0.227</p>
</td>
<td>
<p>0.227</p>
</td>
<td>
<p>0.183</p>
</td>
<td>
<p>0.334</p>
</td>
</tr>
<tr>
<td>
<p>The depth of gastric pits/ Глубина ямок</p>
</td>
<td>
<p>0.038</p>
</td>
<td>
<p>0.840</p>
</td>
<td>
<p>0.059</p>
</td>
<td>
<p>0.753</p>
</td>
</tr>
<tr>
<td>
<p>The glands length/ Длина желез</p>
</td>
<td>
<p>0.085</p>
</td>
<td>
<p>0.650</p>
</td>
<td>
<p>0.114</p>
</td>
<td>
<p>0.543</p>
</td>
</tr>
<tr>
<td>
<p>The height of the integumentary epithelium/ Высота покровного эпителия</p>
</td>
<td>
<p>0.039</p>
</td>
<td>
<p>0.836</p>
</td>
<td>
<p>0.061</p>
</td>
<td>
<p>0.746</p>
</td>
</tr>
<tr>
<td>
<p>The height of glandular epithelium/ Высота железистого эпителия</p>
</td>
<td>
<p>0.088</p>
</td>
<td>
<p>0.642</p>
</td>
<td>
<p>0.046</p>
</td>
<td>
<p>0.807</p>
</td>
</tr>
<tr>
<td>
<p>The number of parietal cells/ Число париетальных клеток</p>
</td>
<td>
<p>0.354</p>
</td>
<td>
<p>0.037</p>
</td>
<td>
<p>0.339</p>
</td>
<td>
<p>0.046</p>
</td>
</tr>
<tr>
<td colspan="5">
<p><em>Note.</em>Pearsons linear coefficient Spearmans rank correlation coefficient were used*<em>р</em>bilateral significance.The values of the modulus of the correlation coefficientand Linear quality characteristic: |<em>r</em>| 0.3weak. 0.3 |<em>r</em>| 0.5moderate. 0.5 |<em>r</em>| 0.7significant. 0.7 |<em>r</em>| 0.9strong. 0.9 |<em>r</em>| 1very strong.</p>
<p><em>Примечание</em><em>.</em>Использованы выборочный коэффициент Пирсона иранговый коэффициент Спирмена. *<em>р</em> значимость двусторонняя. Значения модуля коэффициента корреляции икачественная характеристика линейной связи. |<em>r</em>| 0.3 слабая. 0.3 |<em>r</em>| 0.5 умеренная. 0.5 |<em>r</em>| 0.7 значительная. 0.7 |<em>r</em>| 0.9 сильная. 0.9 |<em>r</em>| 1 очень сильная.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>When analyzinga linear correlation between the level of hemoglobin and indicatorsof the peptic function of the stomach in the groups,no statistically significant relationship was obtained. A significant inverse correlationwas obtained between the level of hemoglobin and the levelof antibodies to Castles factor in Group 1. The analysisof all groups revealed a weak, direct, and statistically significantcorrelation between the level of hemoglobin and pepsinogen Ianda weak, negative, inverse statistically significant correlation with the levelof antibodies to Castles factor. The data are presented inTable 5.</p>
<p></p>
<p><em>Table5/ </em><em>Таблица</em><em> 5</em></p>
<p>Analysis of the linear correlation between the level of hemoglobin and parametrs of peptic function of the stomach and the level of antibodies to Castles intrinsic factor</p>
<p>Анализ линейной корреляционной связи уровня гемоглобина и показателей пептической функции желудка, уровня антител к фактору Кастла</p>
<table>
<thead>
<tr>
<td>
<p>Parameter/ Показатель</p>
</td>
<td>
<p>Pearsons coefficient/Коэффициент Пирсона</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
<td>
<p>Spearmans coefficient/ Коэффициент Спирмена</p>
</td>
<td>
<p><em>р</em>*</p>
</td>
</tr>
</thead>
<tbody>
<tr>
<td colspan="5">
<p>Group1 / Группа 1</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/ ПепсиногенI</p>
</td>
<td>
<p>0.276</p>
</td>
<td>
<p>0.172</p>
</td>
<td>
<p>0.268</p>
</td>
<td>
<p>0.186</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenII/ ПепсиногенII</p>
</td>
<td>
<p>0.001</p>
</td>
<td>
<p>0.998</p>
</td>
<td>
<p>0.216</p>
</td>
<td>
<p>0.289</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/PepsinogenII /ПепсиногенI/ПепсиногенII</p>
</td>
<td>
<p>0.276</p>
</td>
<td>
<p>0.172</p>
</td>
<td>
<p>0.271</p>
</td>
<td>
<p>0.181</p>
</td>
</tr>
<tr>
<td>
<p>Antibodies to Castles intrinsic factor/ Антитела кфактору Кастла</p>
</td>
<td>
<p>0.529</p>
</td>
<td>
<p>0.006</p>
</td>
<td>
<p>0.418</p>
</td>
<td>
<p>0.034</p>
</td>
</tr>
<tr>
<td colspan="5">
<p>Group2 / Группа 2</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/ ПепсиногенI</p>
</td>
<td>
<p>0.273</p>
</td>
<td>
<p>0.177</p>
</td>
<td>
<p>0.328</p>
</td>
<td>
<p>0.102</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenII/ ПепсиногенII</p>
</td>
<td>
<p>0.222</p>
</td>
<td>
<p>0.276</p>
</td>
<td>
<p>0.349</p>
</td>
<td>
<p>0.081</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/PepsinogenII /ПепсиногенI/ПепсиногенII</p>
</td>
<td>
<p>0.140</p>
</td>
<td>
<p>0.494</p>
</td>
<td>
<p>0.146</p>
</td>
<td>
<p>0.477</p>
</td>
</tr>
<tr>
<td>
<p>Antibodies to Castles intrinsic factor/ Антитела кфактору Кастла</p>
</td>
<td>
<p>0.238</p>
</td>
<td>
<p>0.242</p>
</td>
<td>
<p>0.385</p>
</td>
<td>
<p>0.052</p>
</td>
</tr>
<tr>
<td colspan="5">
<p>Group3 / Группа 3</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/ ПепсиногенI</p>
</td>
<td>
<p>0.076</p>
</td>
<td>
<p>0.662</p>
</td>
<td>
<p>0.056</p>
</td>
<td>
<p>0.748</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenII/ ПепсиногенII</p>
</td>
<td>
<p>0.211</p>
</td>
<td>
<p>0.224</p>
</td>
<td>
<p>0.101</p>
</td>
<td>
<p>0.563</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/PepsinogenII /ПепсиногенI/ПепсиногенII</p>
</td>
<td>
<p>0.229</p>
</td>
<td>
<p>0.185</p>
</td>
<td>
<p>0.255</p>
</td>
<td>
<p>0.139</p>
</td>
</tr>
<tr>
<td>
<p>Antibodies to Castles intrinsic factor/ Антитела кфактору Кастла</p>
</td>
<td>
<p>0.042</p>
</td>
<td>
<p>0.813</p>
</td>
<td>
<p>0.052</p>
</td>
<td>
<p>0.768</p>
</td>
</tr>
<tr>
<td colspan="5">
<p>In all studied patients/ Среди всех исследуемых больных</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/ ПепсиногенI</p>
</td>
<td>
<p>0.243</p>
</td>
<td>
<p>0.024</p>
</td>
<td>
<p>0.190</p>
</td>
<td>
<p>0.078</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenII/ ПепсиногенII</p>
</td>
<td>
<p>0.133</p>
</td>
<td>
<p>0.218</p>
</td>
<td>
<p>0.109</p>
</td>
<td>
<p>0.316</p>
</td>
</tr>
<tr>
<td>
<p>PepsinogenI/PepsinogenII /ПепсиногенI/ПепсиногенII</p>
</td>
<td>
<p>0.049</p>
</td>
<td>
<p>0.650</p>
</td>
<td>
<p>0.040</p>
</td>
<td>
<p>0.710</p>
</td>
</tr>
<tr>
<td>
<p>Antibodies to Castles intrinsic factor/ Антитела кфактору Кастла</p>
</td>
<td>
<p>0.012</p>
</td>
<td>
<p>0.913</p>
</td>
<td>
<p>0.280</p>
</td>
<td>
<p>0.009</p>
</td>
</tr>
<tr>
<td colspan="5">
<p><em>Note</em>.Pearsons linear coefficient Spearmansrank correlation coefficient were used. *<em>р</em>,bilateral significance.The values of the modulus ofthe correlation coefficient and Linear quality characteristic: |<em>r</em>| 0,3weak, 0,3 |<em>r</em>| 0,5moderate, 0,5 |<em>r</em>| 0,7significant, 0,7 |<em>r</em>| 0,9strong, 0,9 |<em>r</em>| 1very strong.</p>
<p><em>Примечание.</em>Использованы выборочный коэффициент Пирсона иранговый коэффициент Спирмена. *<em>р</em> значимость двусторонняя. Значения модуля коэффициента корреляции икачественная характеристика линейной связи: |<em>r</em>| 0,3 слабая, 0,3 |<em>r</em>| 0,5 умеренная, 0,5 |<em>r</em>| 0,7 значительная, 0,7 |<em>r</em>| 0,9 сильная, 0,9 |<em>r</em>| 1 очень сильная.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>At that, the average levels of antibodies toCastles factor in the groups did not statistically differ; they were<sub>2.53</sub>4.06<sub>5.54</sub>in Group 1,<sub>1.83</sub>3.12<sub>4.41</sub>in Group 2, and<sub>1.37</sub>8.03<sub>17.42</sub>in Group 3 (<em>p</em><sub>1,2</sub>=0.347;<em>p</em><sub>1,3</sub>= 0.464;<em>p</em><sub>2,3</sub>= 0.368). Increasedlevel was noted in 4.76% in Group 1 and 4.4% in Group 3, andin Group 2, there were no such patients (0%;<em>р</em><sub>1,2</sub>= 0.083;<em>р</em><sub>1,3</sub>= 0.945;<em>р</em><sub>2,3</sub>= 0.096). The frequency of helicobacteriosis detection washistologically equal in all the studied groups (63.8% in group1, 53.1% in group2, and 68.1% in group 3;<em>p</em><sub>1,2</sub>= 0.387;<em>p</em><sub>1,3</sub>= 0.954;<em>p</em><sub>2,3</sub>= 0.420).</p>
<h2>DISCUSSION</h2>
<p>Iron malabsorption in patients with celiac disease, who donot follow GFD, is known to lead to anemia[9].In our study, the prevalence of anemia among pediatric patientswho did not receive GFD was 18.9% and was significantlyhigher when comparing pediatric patients with celiac disease who receivedGFD for at least a year with the control group.Compared with other studies, the incidence of anemia was low,but not the least among those described in the literature.This indicator is close to that among Finnish children, accordingto the study in 2017 (prevalence of 18%)[22]. Thehighest incidence of anemia of up to 85% has beenregistered in India [16, 21], while in the developed countriesof Europe and the USA, this indicator is 20%[11,18]. The authors note that this indicator depends on theeconomic situation, and the incidence of anemia reflects the differencesin the clinical presentation of celiac disease. In developing countries,the prevalence of severe forms of celiac disease is higher,and mainly typical forms of gastrointestinal symptoms are detected, whereasin developed countries, the atypical forms predominate. Studies have shownthat patients with celiac disease combined with anemia (both adultsand children) show a higher level of autoantibodies and amore pronounced degree of atrophy of DMM than patients withoutanemia [3, 22]. Our study demonstrates the correlation between thelevel of hemoglobin and the degree of DMM atrophy, aswell as with all the key indicators characterizing atrophy, namely,the height of the villi and the depth of thecrypts and their ratio. The data obtained confirm the importanceof malabsorption in the development of anemia.</p>
<p>It is known thatceliac disease is accompanied by autoimmune lesion of the stomach[1, 2, 2325]. AGis a known cause of perniciousanemia in middle-aged and elderly people and is usually manifestedby cobalamin deficiency and megaloblastic anemia. However, the role ofIDA has recently been described as a recognized complication ofachlorhydria. The relationship of helicobacteriosis with IDA has also beendescribed [26]. It was revealed that IDA is more commonin pediatric patients with AG, while pernicious anemia is themost common hematological condition for adults and elderly patients [6,12, 13]. Atthe same time, population studies on theprevalence of AG among pediatric patients with celiac disease havenot been conducted. Although celiac disease is a systemic autoimmunedisease, the incidence of AG in our study did notexceed the control group. However, among patients with newly diagnosedceliac disease, a statistically significant inverse correlation was revealed betweenthe level of antiparietal antibodies and the level of hemoglobin.In addition, the hemoglobin level showed a direct correlation withthe count of parietal cells. The incidence of helicobacteriosis washistologically the same in all studied groups.</p>
<h2>CONCLUSION</h2>
<p>Thus, in addition tomalabsorption, AG may be a possible cause of anemia asan additional risk factor in pediatric patients with celiac disease.Further studies are required with a large number of participants,the determination of various types of antiparietal antibodies, and indicatorsof iron metabolism to assess the severity of the irondeficiency and normalization of its indicators when following the diet.</p>[Новикова В.П., Шаповалова Н.С., Ревнова М.О., и др. Желудок как орган-мишень целиакии // Педиатр. – 2018. – Т. 9. – № 4. – С. 64–72. [Novikova VP, Shapovalova NS, Revnova MO, et al. The stomach as the target organ of celiac disease. Pediatrician (St. Petersburg). 2018;9(4):64-72. (In Russ.)]. https://doi.org/10.17816/PED9464-72.][Ревнова М.О., Новикова В.П., Шаповалова Н.С., и др. Распространенность аутоиммунного гастрита у детей с целиакией по данным ИФА и реакции непрямой иммунофлюоресценции // Вопросы детской диетологии. – 2017. – Т. 15. – № 2. – С. 55–56. 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