[INTESTINE MICROBIOTA IN CHILDREN WITH OBESITY AND ALLERGIC DISEASES].

AIM: Study intestine microflora in children with obesity and evaluate its association with allergic diseases. MATERIALS AND METHODS. 66 children with various body weight aged 3 to 17 years were included into the study. Intestine microflora study in children was carried out according to the order of the Ministry of Health of Russian Federation No. 231 of 09.06.2003 "Regarding approval of sectoral standard "Patient management protocol. Intestine dysbacteriosis" (SST 91500.11.0004-2003). RESULTS: In healthy children depending on body weight an increase of the number of Firmicutes type microorganisms and a decrease of the number of microbes, belonging to Bacteroidetes type, was detected. The presence of allergic pathology was accompanied by a decrease of the number of Bacteroidetes and the presence of Bacillus and Staphylococcus aureus regardless of the body weight. At the same time, in all the children an increase of the content of Clostridium with the increase of body mass was noted. CONCLUSION. The data obtained have revealed an association of changes in intestine microbiota with the development of obesity and allergopathology.

[Intestine microbiota and allergic diseases].

In industrialized countries an increased number of diseases due to immune system disorders including connected with allergy is noted. Allergic diseases generally proceed against the background of various common inflammatory diseases arising in childhood. The role of intestine microflora in its interaction with immune system and defining factors in allergization of children are actively studied. A decrease of risk of allergy development later in life for children who had grown up in the countryside was shown to be possibly related with microorganisms present in food. Thus the positive potential of farms is currently examined as a result of innate immunity activation by using microbial components. Acinetobacter lwoffii F78 isolated from cowsheds is able to protect mice from experimental allergy by activating Th1-polarization program of dendritic cells. Moreover, an important role in pathogenesis of allergic diseases belongs to mast cells. Probiotic lactobacilli may weaken activation of mast cells and release of inflammation mediators connected with allergic reactions. The ability of intestine microflora to influence immune response resulted in novel approaches in therapy that use these differences in microbiota for therapy and prophylaxis in allergy patients. And therefore on the basis of "hygiene hypothesis" of allergy emergence, a consideration is expressed that early manipulation with intestinal microbial communities may offer a new strategy of allergic sensibilization prevention.

[Evaluation of some immunological indexes in children with allergic diseases and obesity].

AIM: Study some immunological indexes in children with allergic diseases depending on bodyweight and clinical manifestations of allergy. MATERIALS AND METHODS: A correlation analysis of relationship of indexes of natural resistance (phagocytosis, complement), immunoglobulin level and main lymphocyte populations with body weight in 214 children aged 12 - 17 years with various allergic diseases (rhinitis/ rhinoconjunctivitis, atopic dermatitis, bronchial asthma) was carried out. The children were divided into groups based on body mass index (BMI): 73 (34%) children with normal weight, 74 (35%) overweight and 67 (31%) obese. RESULTS: The analysis has shown that the frequency of detection of children with obesity is the highest for age 12 - 14 years. With the increase of age the number of obese children decreases (OR - 9.0; 95% CI: 1.56 - 51.87; p = 0.008 and OR - 0.27; 95% CI: 0.08 - 0.94; p = 0.04, respectively). An interrelation of BMI with clinical exacerbations of allergy was detected. Out of 166 patients with allergic diseases combined with bronchial asthma excessive weight was detected in 62 (37%), obesit--in 57 (34%) and normal weigh--in 47 (28%). In a group of 48 children with allergy without asthma excessive weight was noted in 12 (25%), obesit--in 10 (21%) and normal weigh--in 26 (54%) of patients. In children with bronchial asthma excessive weight occurs almost 3 times more frequently than in children with allergy and without asthma. Differences could not be detected in 3 groups of children when immune status indexes were compared, except total IgE and NK cell levels. Total IgE level was the highest in obese children (2.7 log), differed significantly from the level in obese (2.46 log) and normal weight (2.37 log, r = 0.32, p < 0.05) children. The relative content of NK cells in blood of obese children was significantly higher than in children withnoormal and excessive weight (r = 0.41). The analysis of significant correlation coefficient indexes detected correlative associations of some immunological indexes with BMI. In overweight children a negative relation between the level of complement and BMI (r = -0.61) and positive relation with phagocytosis index (r = 0.58) were detected. CONCLUSION: Obesity in children with allergic diseases is associated with an increase of conjugation of immunological indexes manifesting in an increase of number of natural killers (NK), phagocytosis indexes, increased total IgE level against the background of negative interrelation with the main populations of lymphocytes, that in general influences aggravation of allergopathology in the form of a higher frequency of detection of atopic bronchial asthma.

[Mucosal immune response to Helicobacter pylori in children with gastroduodenal diseases and allergy].

In children with chronic gastritis/gastroduodenitis, erosions and ulcer of stomach and duodenum and associated allergic diseases (asthma, allergic rhinitis, atopic dermatitis) CagA, sIgA and IgE antibodies to the H. pylori were determined by ELISA in the supernatants of feces. H. pylori infection was determined according to "Maastricht IV". The frequency and contents of CagA did not differ among the groups we studied. However, in children with positive urease test the contents of CagA was significantly higher (p = 0.03) compared with other children. The highest levels of sIgA were found in the feces supernatants from non-allergic children with CG/CGD and were associated with H. pylori infection. The immune response in children with erosions and ulcer of stomach and duodenum and in children with allergy was presented the sIgE to H. pylori. Also, the negative correlation between the level sIgE to H. pylori and content sIgA was found in children with allergy. Thus, increased IgE indicates not only allergy, but also acts as a protective role in the development of anti-infective immunity.

[IgE-antibodies to Helicobacter pylori in children with gastroduodenal diseases and concomitant of allergy].

In children with chronic gastritis/gastroduodenitis (CG/CGD), ulcerative and erosive processes of mucous and associated allergic diseases IgM, IgA, IgG, and IgE to the H. pylori were determined by ELISA in the blood serum. IgM-antibodies to H. pylori were found in isolated cases and did not present a diagnostic significance. IgG-antibodies were detected in all children in the same percentage (40-50%), pointing indirectly to the widespread contamination by H. pylori. IgA-antibodies to H. pylori with high frequency (83% and 57%) were found in the blood serum of children with the diseases of gastroduodenal zone without allergies, while in children with allergic pathology they were found by 3-4 times less (20%). IgE antibodies to H. pylori were determined in a high percentage of cases in healthy children (86%) and allergic children (75%), while children without allergy IgE antibodies were detected in the 54-65% of cases. In this study, the detection of IgE antibodies to H. pylori has allowed to increase the frequency of the diagnosis of helicobacteriosis cases in children with gastropathology by 16% in general and in the group of children with allergic diseases this increase amounted to 27.3%. Moreover, children with antihelicobacterial IgE antibodies in a large percentage of cases (92-94%) revealed a positive urease activity. Detection of serum IgE-antibodies to H. pylori in combination with other antibodies isotypes in children increases the diagnostic significance of determination of H. pylori infection and may be recommended when applying serodiagnosis H. pylori in children's practice, especially in children with allergic pathology.

Oct-1 is responsible for the C-33T polymorphism effect in the IL-4 promoter.

IL-4 is a pleiotropic immunoregulatory cytokine secreted by Th2 subset of CD4(+) Th cells. Several transcription factors (TFs) have been determined with various degrees of certainty to bind the IL-4 promoter and to regulate its expression in human. To investigate the mechanisms responsible for phenotypic effects of the C-33T IL-4 promoter polymorphism, we performed a search of TFs binding to this promoter locus and discriminating the -33C and -33T alleles. In silico searches suggest few factors bind this region. Using an electromobility shift assay we found that Jurkat T cells contained proteins which specifically interacted with oligonucleotide probes, corresponding to the -33 region. Considerable binding differences between C and T alleles were demonstrated using competitive conditions, the proteins bound predominantly with -33C allele. We found that the transcription factor Oct-1 produced the major shifted complex. The binding of Oct-1 was not improved using activated nuclear extracts; however, we observed increases in other shifted complexes upon cell activation. We suppose that Oct-1 occupancy may compete for binding of activator proteins to closely or overlapped binding sites. Our findings suggest that the interplay between Oct-1 and unknown TFs may be responsible for the C-33T polymorphism effects.

[IgE-autoantibodies in patients with atopic dermatitis].

Atopic dermatitis (AD) is a complicated and multifactorial disease. Autoimmune reactions to own antigens (Ag) revealed in AD patients can aggravate a clinical course of this disease. The aim of the study was to identify IgE antibodies (IgE-Abs) to tissue Ags in AD patients and to evaluate a relationship between the levels of these IgE-Abs and the level of the total IgE. Serum samples from 75 AD patients and 24 healthy persons of different age were examined with enzyme immunoassay for IgE-Abs to 7 tissue Ags (keratin, collagen of type III and VI, elastin, myosin, myelin basic protein - MBP, thyroglobulin), total IgE and IgE-Abs to exoallergens. The levels of IgE-Abs to all investigated tissue Ags (except for MBP) were higher (p < 0.05) in AD patients than in healthy persons. Incidence rate of IgE-Abs to various tissue Ags varied widely (39-78%) and did not depend upon age. Significant correlations were found between the levels of IgE-Abs to collagen of type VI (r = 0.32), thyroglobulin (r = 0.78) and of total IgE. Therefore, most of stimulating IgE-autoreactivity Ags are involved in the pathologic process in AD, keratin, collagen of type IV, thyroglobulin being more important. This may aggravate an AD course.

[H. pylori in development of allergic diseases in patients with gastroduodenal diseases].

AIM: To discover relations between allergic diseases and H. pylori infection in patients with gastroduodenal diseases. MATERIAL AND METHODS: The study was made of 113 patients (age 22-65, 34 males and 79 females) with chronic gastritis and duodenal ulcer. Of them, 60 patients (group 1) had concomitant allergy (urticaria, bronchial asthma, atopic dermatitis, food allergy, pollinosis), while 53 patients (group 2) had no allergy. H. pylori infection was diagnosed with the respiratory and rapid urease test, histological and cytological tests. Enzyme immunoassay determined total antibodies (AB) to H. pylori in IgG, IgA, IgM classes; IgA-AB in the kits Vector Best (Russia), IgG-AB to H. pylori in the kits of ECOLab (Russia) and total IgE in the kits IgE-EIA (Stavropol). RESULTS: In group 1 total AB to H. pylori were positive in 48 (80%), IgG-AB and IgA-AB to H. pylori in 38 (63.3%) and 43 (71.6%) patients, respectively. In elevated concentration of AgG-AB to H. pylori 46 (76.6%) patients had elevated total IgE (mean 364 IU.l). In group 2 total AB to H. pylori were detected in 45 (85.0%) patients, IgG-AB and IgA-AB to H. pylori in 47 (88.6%) and 32 (60.3%), respectively. Among patients with high level of IgG-AB to H. pylori in the serum high total IgE was only in 35.8% patients. Mean IgE was 250 IU/l. CONCLUSION: Patients with gastroduodenal diseases associated with H. pylori and allergy and not associated had similar level of total AB to H.pylori, while higher total IgE and specific IgE-AT to H. pylori occurred in the former. Thus, H. pylori infection is associated with allergic (atopic) immune response.

Allelic polymorphisms in the interleukin-4 promoter regions and their association with bronchial asthma among the Russian population.

BACKGROUND: Susceptibility to the development of bronchial asthma (BA) and other atopic diseases is known to be associated with genetic components. OBJECTIVE: To evaluate the possible role of the polymorphisms in IL-4 gene promoters (C-33T, C-590T and G-1098T) in modulating allergic response and asthma in the Russian population. METHODS: The polymorphism analysis was carried out by PCR-RFLP; IL-4 and total IgE concentrations were determined by ELISA. RESULTS: In the case group, the T allele was found at frequencies of 74% (C-33T), 51% (C-590T) and 5% (G-1098T); in the control group the frequencies were 22, 42 and 8%, respectively. Only the C-33T polymorphism was associated with BA. The concentrations of total IgE and serum IL-4 were raised in the case group, while in the control group they were normal. Serum IL-4 level depended on C-33T polymorphism both in the case and control groups, the mutant T allele promoting its increase. The dependence on C-590T polymorphism was detected only in the case group. As for the total IgE level, in both cases it depended on the polymorphism in the case group rather than the control. G-1098T polymorphism did not demonstrate any correlations with total IgE or serum IL-4 levels. All 3 polymorphisms did not affect the severity of BA in the case group. On the basis of the computer analysis, we propose that the T-33C region is the CREB-binding site. CONCLUSIONS: Our data suggest that IL-4 promoter polymorphism in the Russian population might play a role both conferring susceptibility to BA and modulating the levels of serum IL-4 and total IgE.

[Prevalence and structure of acute respiratory virus infections]. / Rasprostranennoct' i struktura ostrykh respiratornykh virusnykh infektsii.

Information on epidemiology of acute respiratory virus infections (ARVI) is reviewed and analyzed. In addition to influenza viruses, the role of respiratory syncytial viruses (RSV), rhino- and adenoviruses, as well as other viruses, in the development of respiratory diseases, especially in newborns, young children and elderly persons, is emphasized. A high proportion of RSV in the etiology the severe forms of ARVI and in the development of intrauterine infection is pointed out. The conclusion has been made that the identification of the causative agents of ARVI with the use of modern methods makes it possible to determine the real role of each of the pathogens in the formation of the severe forms of diseases, as well as the expediency of vaccinal prophylaxis.

[Diagnostic and prognostic significance of the antibodies to the myelin basic protein in acute neuroinfections in children]. / Diagnosticheskoe i prognosticheskoe znachenie antitel k osnovnomu belku mielina pri ostrykh neiroinfektsiiakh u detei.

The development of severe CNS damages including encephalitis is highly probable in some respiratory and exanthemata viral infections (measles, rubella, parotitis). A high level of IgG antibodies to the myelin basic protein was found in patients with parotitis meningitis and rubella encephalitis but it was not high in 80% of patients with encephalitis of the unclear etiology and in 25% of cases with rubella encephalitis. More accurate analysis of clinical, neurovisual and immunologic data revealed a link of appearance of such complications with both the presence of more pronounced demyelinization and prolongation of the disease.

[Allergic alteration of leukocytes in patients with drug intolerance]. / Allergicheskaia al'teratsiia leikotsitov u bol'nykh lekarstvennoi neperenosimost'iu.

Increased sensitivity to benzylpenicillin, ampicillin, claforan, cefzol, novocain and lidocaine was determined by means of the leukocyte allergic alteration (LAA) test in 599 patients with intolerance reactions to these preparations in their medical history. In most of these patients the test results exceeded 30% and reached 98%, their average values exceeding those in the control group no subjects with no drug intolerance. The LAA test ensured a high level (83%) of the detection of drug intolerance.

[Investigation on the mechanisms of leukocyte alteration in patients with intolerance to some drugs (with novocaine as a model)]. / Issledovanie mekhanizmov al'teratsii leikotsitov u bol'nykh s neperenosimost'iu nekotorykh lekarstv (na modeli novokaina).

The mechanisms of novocain damaging action on blood cells in persons with increased sensitivity to this drug were studied in the leukocyte alteration test. The leading role of histamine liberated from basophils was established. The increased sensitivity to novocain was shown not to be passively transferred to the cells of healthy donors with patient serum with intolerance to the drug; moreover, the joint action of both cell-mediated and thermolabile humoral factors was found to be necessary for the realization of leukocyte alteration under the action of novocain. The comparison of the information content of a number of methods--skin testing, dosed provocation, leukocyte alteration test and chemiluminescence--for revealing increased sensitivity to novocain in 30 persons with adverse reactions to this preparation registered in their medical history. The two in vitro tests were shown to be comparable in their diagnostic significance with the method of dosed provocation.

[An allergen from Blattella germanica cockroaches and its immunological properties]. / Allergen iz tarakanov Blattella germanica i ego immunologicheskie svoistva.

The optimum method for obtaining allergenic preparation with high specific activity and stable physico-chemical characteristics from cockroaches of the species B. germanica was developed. The quantitative content of cockroach allergens Bla g1 and Bla g2 was determined in experimental batches. The age structure of sensitization to cockroaches in 124 bronchial asthma patients (50 adults and 74 children) was studied. Specific IgE antibodies to B. germanica were detected in 34% of the examined adults and 63.5% of the children.

[The detection of house dust mites in the apartments of children with allergic diseases]. / Obnaruzhenie kleshchei domashnei pyli v kvartirakh u detei s allergicheskimi zabolevaniiami.

The acarological study of house dust in 239 apartments of children with different allergic diseases (bronchial asthma, rhinosinusitis, atopic dermatitis) developing as the result of indoor sensitization has been carried out. The significant difference between the occurrence of house-dust mites in apartments inhabited by healthy and sick children has been established. The occurrence of mites and their number have been found to affect the symptoms of an allergic disease and its exacerbation.

[Clinico-microbiological assessment of therapeutic antifungal drugs therapeutic activity in patients with atopic dermatitis sensitized to yeast fungi]. / Kliniko-mikrobiologicheskaia otsenka terapevticheskoi éffektivnosti protivogribkovykh preparatov u bol'nykh atopicheskim dermatitom, sensibilizirovannykh k drozhzhepodobnym gribam.

AIM: To study of therapeutic activity of local (natamycine) and systemic (fluconasol) antifungal drugs in patients with atopic dermatitis (AD) with mycogenic sensitization and candida carriage. MATERIALS AND METHODS: 29 patients with severe AD and diagnosed contamination of the skin lesions with yeast fungi have received antifungal treatment with fungicidal drugs in low-dose long-term course. RESULTS: The drugs were effective in 83% of patients: poor effect was in 28%, moderate--in 21% and good--in 34% of cases. 5 (17%) patients did not respond. Mild, moderate and severe AD responded in 87, 36 and 60% of patients, respectively. The highest response was registered in patients without sensitization to yeast fungi (78%) or low sensitization (83%). In high sensitization the effect occurred in 57% of the cases. CONCLUSION: The authors have developed indications for treatment with antifungal drugs in AD patients with mycogenic sensitization.