The utility of TNF-alfa, IL-6 and IL-10 in the diagnosis and/or follow-up food allergy

Background: Several pro-inflammatory and anti-inflammatory mediators play a role in the immunopathogenesis of food allergy (FA). The aim of this study was to investigate the utility of serum biomarkers like interleukin (IL)-10, TNF-alfa, and IL-6 in the diagnosis and/or follow-up of FA. Methods: Sixty (25 females, 41.6%) newly diagnosed FA patients [IgE mediated (group-1, n = 37), non-IgE (group-2, n = 23)] with a median age of nine (1-33) months were enrolled. Twenty-four healthy children with a median age of eight (1-36) months constituted the control group (CG). In all the subjects, serum TNF-alfa, IL-6 and IL-10 levels were evaluated at the time of diagnosis and reassessed four weeks after therapeutic elimination diet (TED). Results: The mean white blood cell count and median absolute eosinophile count of the CG were significantly lower than group-1 (p values were 0.019 and 0.006, respectively). The mean absolute neutrophile count and the median IL-6 were significantly higher in group-1 when compared with group-2 (p values were 0.005 and 0.032, respectively. Median TNF-alfa and IL-6 levels were significantly higher in the pre-TED among all patients (p values were 0.005 and 0.018, respectively). In group-1, median TNF-α and IL-6 levels decreased significantly after TED (p values were 0.01 and 0.029, respectively). Conclusions: Our findings support the role of inflammation in the pathogenesis of FA. Serum TNF-alfa and IL-6 levels may be useful markers for follow-up in FA, especially among IgE-mediated FA patients. Evaluation of IL-10 results was not sufficient for an interpretation of clinical tolerance

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The utility of TNF-α, IL-6 and IL-10 in the diagnosis and/or follow-up food allergy.

BACKGROUND: Several pro-inflammatory and anti-inflammatory mediators play a role in the immunopathogenesis of food allergy (FA). The aim of this study was to investigate the utility of serum biomarkers like interleukin (IL)-10, TNF-α, and IL-6 in the diagnosis and/or follow-up of FA. METHODS: Sixty (25 females, 41.6%) newly diagnosed FA patients [IgE mediated (group-1, n=37), non-IgE (group-2, n=23)] with a median age of nine (1-33) months were enrolled. Twenty-four healthy children with a median age of eight (1-36) months constituted the control group (CG). In all the subjects, serum TNF-α, IL-6 and IL-10 levels were evaluated at the time of diagnosis and reassessed four weeks after therapeutic elimination diet (TED). RESULTS: The mean white blood cell count and median absolute eosinophile count of the CG were significantly lower than group-1 (p values were 0.019 and 0.006, respectively). The mean absolute neutrophile count and the median IL-6 were significantly higher in group-1 when compared with group-2 (p values were 0.005 and 0.032, respectively. Median TNF-α and IL-6 levels were significantly higher in the pre-TED among all patients (p values were 0.005 and 0.018, respectively). In group-1, median TNF-α and IL-6 levels decreased significantly after TED (p values were 0.01 and 0.029, respectively). CONCLUSIONS: Our findings support the role of inflammation in the pathogenesis of FA. Serum TNF-α and IL-6 levels may be useful markers for follow-up in FA, especially among IgE-mediated FA patients. Evaluation of IL-10 results was not sufficient for an interpretation of clinical tolerance.

The frequency of celiac disease in children with autoimmune thyroiditis.

BACKGROUND AND AIMS: Although the presence of autoimmune thyroiditis (AT) in celiac disease (CD) has been well documented among adults, CD in AT has been less reported in children. We aimed to investigate the frequency of CD in children with AT. Materials and Methods : This prospective study was carried out from October 2015 to August 2016 and included 66 patients with AT. Firstly, total IgA and tissue transglutaminase antibody (tTG) IgA levels were measured. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastroduodenoscopy for a definitive diagnosis of CD. RESULTS: Sixty-six patients with AT (52 female) with mean age of 14.68 ± 3.18 years were enrolled. IgA deficiency was found in four patients. Only three of 66 patients (4.5%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA, and only one of them (1.5%) had positive EMA antibodies. Gastroduodenoscopy was performed in this patient. The result of pathological investigation was compatible with CD. Furthermore, one patient with AT had been diagnosed with CD previously. CONCLUSIONS: Two (3.0%) of 66 patients with AT were found to have CD. According to the results, we assume that there is a close relationship between CD and AT disease. However, there is a need for multicentric, prospective studies that would support our findings.

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

BACKGROUND: The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. METHODS: We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. RESULTS: Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). CONCLUSION: In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Significance of Doppler ultrasonography in the diagnosis of polycystic ovary syndrome.

OBJECTIVE: To investigate the importance of transvaginal color Doppler ultrasonography of uterine and intraovarian arteries in the clinical diagnosis of polycystic ovary syndrome (PCOS). MATERIAL & METHOD: This study was planned as a cohort, controlled, prospective study. A total of 80 participants (40 with PCOS and 40 as a control group) were enrolled in the study. A Doppler system with a 6.0 MHz transvaginal probe was used when performing ultrasonography (USG) and Doppler examinations. Ovarian size and volume, number of follicles and stromal echogenity were evaluated by USG. Doppler flow studies were targeted to uterine and intraovarian arteries and the pulsatility index (PI) was assessed. The concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (T) and dihydroepiandrostenedione sulphate (DHEAS) were measured by immunometric methods. RESULTS: The mean values of the number of follicles and the ovarian volume of both the right and left ovaries were higher in the group with PCOS than the control group (p < 0.05). The mean PI values of the right and left ovaries, respectively, were 0.84 +/- 0.23 and 1.09 +/- 1.17 in the group with PCOS, and 0.88 +/- 0.14 and 0.92 +/- 0.15 in the control group. The mean PI values of the right and left uterine arteries, respectively, were 3.25 +/- 0.98 and 3.33 +/- 1.12 in the group with PCOS, and 3.17 +/- 0.93 and 3.2 +/- 1.38 in the control group (p > 0.05). The correlation analysis of the ovarian volume, the number of follicles and Doppler parameters revealed that there was a positive correlation and statistically significant difference between the right ovarian volume and right uterine artery PI in the group with PCOS and the left ovarian volume and left uterine artery PI in the control group (p > 0.05). The mean stromal PI of the ovarian and uterine arteries were 0.96 +/- 0.61 and 3.29 +/- 1.02 in the group with PCOS and 0.9 +/- 0.12 and 3.19 +/- 1.14 in the control group, respectively (p > 0.05). In the group with PCOS, the mean ovarian volume and the mean number of follicles were 11.46 +/- 4.43 and 13.91 +/- 4.11, respectively, whereas they were 7.63 +/- 2.44 and 5.55 +/- 2.34 in the control group (p < 0.05). CONCLUSION: It is not beneficial to use color Doppler transvaginal ultrasonography in the clinical diagnosis of patients with PCOS.

Combined administration of misoprostol in the first and second trimester missed abortion cases.

OBJECTIVE: We aimed to investigate the effectiveness and adverse effects of combined (vaginal + oral) administration of misoprostol in missed abortion cases. MATERIAL AND METHODS: 48 missed abortion cases between 8 and 20 weeks of gestation were enrolled in this study. Misoprostol-induced medical abortion was planned; the first dose (200 microg) was administered intravaginally and subsequent doses (200 microg each) orally every following hour. A maximum of six doses (1200 microg) were used. Revision curettage was performed on all subjects who aborted. RESULTS: The mean time interval from the first dose of misoprostol until the abortion was 6.27 +/- 3.02 hours. The success rate was 95% for the whole group. We observed misoprostol-related trembling in one patient and fever in two patients. CONCLUSION: We believe that our low-dose combined misoprostol protocol is a safe, effective and well-tolerated method with minimal adverse effects for the termination of both first and second trimester pregnancy losses.

The role of inhibin B as a basal determinant of ovarian reserve.

Our objective was to compare inhibin B and conventional basal determinants in designating the ovarian reserve in patients receiving assisted reproductive treatment. A total of 58 women, aged 19-47 years, who were accepted for assisted reproductive treatment at the Zeynep Kamil Women and Children's Hospital, Department of Assisted Reproductive Technologies, were included in the study. The age, body mass index, basal levels of follicle stimulating hormone, estradiol and inhibin B, volume of the ovary and number of antral follicles were compared prospectively. When the number of oocytes collected was > or = 5, this was accepted as a sufficient ovarian response. Serum inhibin B (cut-off level 56 pg/ml), as a basal determinant of ovarian reserve, had the highest sensitivity (81%) and specificity (81%). The usefulness of serum inhibin B measurement as a basal determinant of ovarian reserve is supported.

The role of androgens in the aetiology and pathology of pre-eclampsia.

Pre-eclampsia and eclampsia, along with its complications such as prematurity, intrauterine growth retardation, perinatal asphyxia and abruptio placenta, continues to be one of the major causes of maternal and fetal morbidity and mortality. Due to its morbid course, it is necessary to identify those at risk for the illness and take precautions. However, the lack of knowledge about the aetiology makes it difficult to assess risk factors. We studied the role of the serum androgens in the pathogenesis of pre-eclampsia. Ninety severe pre-eclamptic, 10 mild pre-eclamptic and 50 normotensive pregnant women were studied. The patient and control groups' blood total testosterone, free oestriol (FE3), FAI (free androgene index), sex hormone binding globulin (SHBG) and dehydroepiandrostenedione sulphate (DHEA-S) values were compared. The sex, weight, APGAR scores and hospitalisation in the neonatal intensive care unit of the babies were also evaluated. No statistically significant difference in the total testosterone and free oestriol values was found between the groups. SHBG was found to be higher in the pre-eclamptic group, whereas free testosterone and DHEA-S were higher in the normotensive group. Compared to the severe pre-eclamptic group, no difference was found in the total testosterone levels, whereas free testosterone levels were significantly higher in the mild pre-eclamptic group. We reached the opinion that androgens do not play a clinically significant role in the pathogenesis of pre-eclampsia.

HLA-DQ alleles in patients with celiac disease in Turkey.

The prevalence of the HLA-DQA1 and DQB1 alleles in 55 Turkish children with celiac disease and 50 control subjects was investigated by using an allele-specific DNA-based polymerase chain reaction-sequence-specific primer (PCR-SSP) method. The frequency of the DQA1*0501 and DQB1*02 alleles was higher in celiac patients than in controls. The DQA1B1 (*0501; *02) haplotype was present in 46 (83.6%) patients and only in 12 (24%) controls. The remaining 9 celiac patients which were negative for DQA1B1 (*0501;*02) carried the DQA1B1 (*03;*0302) haplotype. We found an excess homozygosity of the DQB1*02 allele and the DQA1B1 (*0501;*02) haplotype in the patients. No statistically significant correlation was found between the homozygosity of this haplotype or the DQB1*02 allele and an earlier onset of the disease.

Human leukocyte antigens in Turkish pediatric celiac patients.

With the aim to determine the frequency of human leukocyte antigen phenotypes of celiac disease in Turkey, thirty celiac patients fulfilling the European Society of Pediatric Gastroenterology and Nutrition criteria were included in the study. The mean age of the study population was 5.8 +/- 4.3 years and of the control subjects was 32.6 +/- 6.7 years. The human leukocyte antigens -A, -B, -DR and -DQ were studied serologically by micro lymphocytotoxic reaction. It was found that human leukocyte antigens A-25(10), -B8, -DR18(3) and -DQ2 were more significantly frequent in the celiac population than in the control group. Children with antigen -B8 showed a five times higher risk for celiac disease and those with antigen -DQ2 showed a nine times higher risk. It was determined that human leukocyte antigen -B4 had a protective role in celiac disease. The study suggests that the human leukocyte antigen -A25(10) is a phenotype particularly encountered in Turkish pediatric celiac patients.

A case of vertical transmission of hepatitis A virus infection.

We present a case of hepatitis A infection in a 2.5-month-old male who became icteric after 18 d of birth. The diagnosis of hepatitis A was made by compatible clinical symptoms, laboratory results and liver biopsy showing evidence of hepatitis, and confirmed by detection of anti-HAV IgM antibodies. Because the mother had an acute icteric hepatitis A 1 week before delivery, and the viraemic phase of hepatitis A infection is very short, approximately 7 d, we suggest that the infant was infected by his mother, before birth.

[Hennekam syndrome]. / Syndrome de Hennekam.

UNLABELLED: Hennekam syndrome is a disorder comprising intestinal lymphangiectasia, facial anomalies and moderate mental retardation. Eight cases have been previously reported. CASE REPORT: A 17-month-old girl was admitted to hospital for peripheral edema. On physical examination, she presented with a normal mental development. Facial anomalies were noted including a flat face, depressed and broad nasal bridge, puffy eye lids, mild down-slanting palpebral fissures, hypertelorism, epicanthal folds, bulbous nasal tip, small mouth, and low set ears. A simian line and haemangiomas on the arms, trunk and left limb were also noted. There was no organomegaly. Laboratory investigations showed iron deficiency anemia, hypoproteinemia, hypogammaglobulinemia and an elevated level of alpha-1 antitrypsin excreted in the feces. Endoscopic investigation and the small bowel biopsy showed findings consistent with lymphangiectasia. The patient did well on 24 hour enteral nutrition including medium-chain triglyceride rich diet and infusion of human albumin. CONCLUSION: We have aimed to remind that Hennekam syndrome should be included in differential diagnosis when intestinal lymphangiectasia are associated with facial anomalies.

[Treatment of chronic viral hepatitis B in children with moderate doses of alpha interferon]. / Traitement de l'hépatite chronique à virus B de l'enfant par des doses modérées d'interféron alpha.

AIM: The alpha interferon treatment criteria have not been established in children with chronic hepatitis B. We report the results of a prospective study. METHODS: Between 1988-1992 14 children (2 girls and 12 boys) with chronic hepatitis B received 3 million U/m2 of interferon alpha three times a week for 6 months. All patients underwent a liver biopsy that showed a pattern of chronic active hepatitis. One patient had cirrhosis. Hepatitis B surface antigen, hepatitis Be antigen and hepatitis B virus DNA had been positive in the serum in all for at least 6 months and anti-delta antibodies were negative in all. Pretreatment aminotransferase levels were at least 1.5 times the upper limit of normal. RESULTS: After treatment patients were followed up for at least one year (mean: 21.5 +/- 8.3 months). At the end of treatment HBV DNA was negative in 13 out of 14 patients and reappeared in one; HBeAg seroconversion was observed in 11 patients with the appearance of anti-HBe antibodies. Six patients lost the HBs antigen within 1 to 14 months after treatment. Anti-HBs antibodies did not appear in any patients and aminotransferase level normalized in 13 patients. Thirteen patients underwent liver biopsy after treatment which showed improvement in 12. CONCLUSIONS: Treatment with alpha interferon at doses of 3 MU/m2 is effective in children with active hepatitis B. Long-term follow up is needed to evaluate the effectiveness of this therapy.

Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.

Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated.