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"Child`s Health" (62) 2015. Тематический выпуск "Детская гастроэнтерология"

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The distribution of HLA- system antigens in children with peptic ulcer

Authors: Sorokman T.V., Popeluk O.-M.V. — Bukovinian State Medical University, Chernivtsi, Ukraine

Categories: Pediatrics/Neonatology

Sections: Clinical researches

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The HLA complex genes gained a great importance as a convenient tool for the study of human susceptibility and resistance to a number of diseases, due to its unique allelic polymorphism and compactness of localization, direct participation of HLA class I and II molecules in conjunction with antigenic sites as part of the macromolecular complex and close relation to the diseases.
Objective: To explore the features of the distribution of HLA-system antigens in children with duodenal ulcer.
Material and research methods. A complex сlinical and paraclinical examination of 120 children with duodenal ulcer (DU), aged 10-18 years was conducted. The comparison group was formed of 100 healthy children of appropriate age (avarage age 13,9 ± 3,1 years). The endoscopy was performed with the aid of fibrogastroduodenoscope "Pentax FG - 24P" for the verification of diagnosis. The definition of helicobacter was performed in bioptates, taken directly during endoscopy of the corpus and antrum of ventricle, and duodenal bulb (Sydney-Houston System, 1996). For the same purpose, the method of enzyme-linked immunosorbent assay was used, which was carried out by conventional method using a set of reagents of «Vectory Best» company, Russia. The HLA-typing of DRB1, DQA1, DQB1 was conducted using the method of sequence-specific probe, specific primers / SSP-sequence / -amplification by primers with allelic specificity. In the statistical analysis of association with HLA-antigens with diseases the following criteria were used: p cor (corrected), relative risk (RR) and diagnostic coefficient (DC). The possibility of differentiation were determined using Fisher's exact test. The criterion for statistical significance level was p <0.05. 
Results of research and their discussion. 47.5% of children of main group and 52% of children of comparison group lived in rural areas. The total number of patients, living in the city of Chernivtsi, was 50% - those with DU and 48% of children of comparison group. The main group of examined children consisted of 54.1% boys and 45.9% girls. 
Pain syndrome was observed in all children. The leading symptom of dyspeptic syndrome among patients was nausea. In children who suffered from DU within one year a reliable tendency to constipation was observed, those who suffered for more than 3 years had a tendency to diarrhea and decreased appetite (p <0.05).
After the conduction of endoscopy investigation it was found out that in most cases ulcerative defect was located on anterior, posterior and antero-posterior walls of the duodenal bulb (41%, 21% and 27% respectively). The most common size of the ulcer was 3-5 mm. In 84% of children the helicobacter-associated DU was diagnosed, and it matches the data given in literature sources. In children with Helicobacter pylori infection the following endoscopic features were observed: hyperemia of the stomach and duodenum, puffiness, vulnerability, thickened mucosa folds, capillaritis of "semolina" type, bulging of mucosa as large and small "pavestones". Poor evacuation function of the stomach was observed in 47 (39.2%) children with DU. The following acid-forming gastric function was identified: 53.3% of children had hyperacidity and 46.7% had normoacidity. The study showed that a number of significant deviations in the frequency of HLA-antigens and their intralocus and interlocus combinations  in the direction of dominance in comparison with control group appears in case of DU.
The following specificities: DRB1 * 11 (RR = 2.16; DK = 2.08); DRB1 * 13 (RR = 4.38); allelic variant DQB1 * 0401/02 (RR = 6.13) occur significantly more often in children with DU. At the same time DQB1 * 0301 genotype, 0302 and haplotype DRB1 * 07 / DQA1 * 0301; DRB1 * 13 / DQ A1 * 0501; DRB1 * 11 / DQ B1 * 0501; DQ A1 * 0102 / DQB1 * 0401/02 are absent among relatively healthy individuals, indicating a high degree of association of DU with mentioned combinations. Specificies of DRB1 * 15, allelic variant DQB1 * 0201; DQB1 * 0301,0301 genotype and haplotypes DRB1 * 15 / DQA1*0101, DRB1 * 15 / DQA1 * 0102, DRB1 * 01 / DQB1 * 0201, DRB1 * 15 / DQB1 * 0301, DQA1 * 0101 / DQB1 * 0201, DQA1 * 0201 / DQB1 * 0201, are significantly rarer among patients with DU, that makes it possible to evaluate these combinations as protective about DU. Genotype DQB1 * 301,0301 and haplotype DRB1 * 5 / DQB1 * 0301 were absent in patients, suggesting that the risk of the development of disease is significantly reduced under the presence of these genetic markers.
A comparative analysis of the approaching of genes in groups of sick boys and girls showed that boys have significantly more often allele DRB1 * 15 and DRB1 * 15 / DQA1 * 0102 and DRB1 * 15 / DQ B1 * 0602/08 haplotypes. In the group of girls significantly more often allelic variant DQV1 * 0301 and DRB1 * 01 / DQA1 * 0102, DRB1 * 11 / DQB1 * 0301, DQA1 * 0102 / DQB1 * 0301 haplotypes were observed. 
The results of the study may also suggest that the role of these alleles, as factors of susceptibility or resistance, predominant ethnic peculiarities in the distribution of HLA - DRB1, DQA1 and DQB1 alleles, because common associations were found in patients residing in other geographic and ethnic regions of the world.
Thus, the duodenal ulcer disease is associated with specific antigens of the HLA-system. The HLA-typing of DRB1, DQA1 and DQB1 genes should be performed in children with hereditary predisposition to peptic ulcer in order to forecaste for the development and course of the disease.


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