Altered serum antibody levels in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

Objectives: This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients. Patients and methods: This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed. Results: The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients. Conclusion: Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.

High fetal bisphenol A exposure enhances IL22 secretion: A proinflammatory cytokine.

BACKGROUND: Bisphenol A (BPA) is an industrial product, widely used in human consumed types of equipment that can be transmitted orally, by inhalation or through dermal absorption and is detectable in many body fluids including cord blood. A correlation between BPA concentration in maternal serum and cord blood has been demonstrated previously, suggesting a possible transfer of BPA via the transplacental path. OBJECTIVE: Our objective is to determine the impact of cord blood BPA level on cytokine responses. METHODS: In this cross-sectional study, healthy pregnant women who delivered healthy newborns followed by the Obstetrics and Gynecology Department between September 2016 to June 2017 were enrolled. Cord blood samples were obtained and BPA and IL4, IL5, IL10, IL17, IL22, IFN gama and TGF beta levels were studied by ELISA. RESULTS: Among 197 deliveries, 176 of them were included in the study. Due to lack of cut-off value, BPA levels were stratified as percentiles. No statistically significant difference was detected in comparison of cytokine levels based on BPA concentrations below and above the 25th and 50th percentiles. Significantly higher IL22 levels (p = 0.007) and increased ratio of IL22/TGFß (p = 0.04) were detected in those with BPA level above 75th percentile (>19.16 ng/ml) compared to the below group. CONCLUSIONS: This in vivo real-life study demonstrated that very high BPA levels in cord blood of expectant mothers enhances IL22 secretion in cord blood which is a proinflammatory cytokine. Studies evaluating long term immunological effects on those highly exposed newborns are necessitated.

Impact of SARS-CoV-2 Delta and Omicron variants on viral burden and cycle threshold in BNT162b2-vaccinated 12-18 years group.

The SARS-CoV-2 pandemic continues to impact the medical, economic, social, and political areas worldwide. Although it has been claimed that children are the most responsible for the outbreaks as of September 2021, the statistics showed controversary. Although it showed no difference in viral load and Ct values between symptomatic children and symptomatic adults, or between asymptomatic children and asymptomatic adults, the molecular mechanism remains unclear. Here, we aimed to investigate the effects of different strains on infection by comparing viral load levels in pediatric patients aged 12-18 years, infected with different variants of SARS-CoV-2, and vaccinated with full-dose BNT162b2. In this retrospective study, a total of 200 patients aged 12-18 years, who were diagnosed with COVID-19 in our hospital, and vaccinated with full-dose BNT162b2, were analyzed according to their gender, age, viral load, and cycle threshold values. Viral RNA levels were evaluated using Ct values, a semi-quantitative proxy of viral load. While the findings did not show a significant difference between gender and age (P = 0.886 and P = 0.897, respectively), a significant difference was found between the Ct and viral load (P < 0.0001). In conclusion, SARS-CoV-2 viral load was higher in cases infected with SARS-CoV-2 Delta variant than SARS-CoV-2 Omicron variant (mean Ct = 23.05 ± 4.06, viral load = 7.8 × 105 copies/ml and mean Ct = 28.04 ± 3.02, viral load = 7.8 × 103 copies/ml, respectively). These findings indicated that the Delta variant had high viral load and our result could be one of the causes the Delta variant was more effective in the pandemic severity than the other variants in the October-December periods when the Delta variant was dominant in Northern Cyprus. During the same period, the severity of the disease was higher, with higher hospitalization and death rates.

The pediatric asymptomatic SARS-CoV-2 IgG seropositivity in the Turkish Republic of Northern Cyprus.

BACKGROUND: While children were initially thought to have serious contributions to the coronavirus disease 2019 (COVID-19) transmission, recent studies suggest otherwise. However, the possible effect of asymptomatic pediatric spread still has not yet received enough attention. The aim of our study was to estimate asymptomatic infection rates among children in the Turkish Republic of Northern Cyprus, by using pediatric patients admitted to a university hospital without any COVID-19-associated symptoms. METHODS: Blood samples collected from 80 pediatric patients with no symptoms and history of COVID-19 infection, who were admitted to a university hospital between September 2020 and January 2021, were included in the retrospective study. Isolated serum samples were tested by Dia.Pro SARS-CoV-2 IgG ELISA assays. RESULTS: The patient group included 40 (50%) male and 40 (50%) female patients. The average age of children was 7.6 ± 4.0 years, with min-max ages ranging from 2 to 15 years. Among the 80 patients tested, only one (1.3%) was detected positive by the Dia.Pro IgG ELISA kit. CONCLUSIONS: The asymptomatic seropositivity reported in our study suggests the use of randomly performed serologic tests to monitor SARS-CoV-2 infection among the pediatric population in schools that would contribute to the public health fight against COVID-19.

Altered tonsillar toll-like receptor (TLR)-1 and TLR-2 expression levels between periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), and group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis patients.

INTRODUCTION: Tonsillar microenvironment is thought to contribute to innate immune dysregulation responsible for the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) because of beneficial effects of tonsillectomy on treatment of the syndrome. Accordingly previous studies reported altered lymphocyte frequency, cytokine level and microbial composition in PFAPA tonsils. The aim of our study is to monitor expression levels of pro-inflammatory cell surface Toll-like receptors (TLRs) which have important role in induction of inflammation and maintaining tissue haemostasis. MATERIALS AND METHODS: Seven patients with PFAPA syndrome, and eight patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis were included in our study. Tonsillar expression levels of TLR-1, -2, -4, -5, and -6 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: IHC analysis demonstrated expression of all TLRs in tonsillar surface epithelium (SE) and lymphoid interior (LI) except for TLR-6 which was not present in the former. There has not been any statistically significant difference in TLR expression levels between PFAPA and GAßHS tonsils, except for TLR-1 and TLR-2 which were higher on LI and lower on SE of PFAPA tonsils, respectively, than that of the GAßHS samples. CONCLUSIONS: Altered TLR expression levels may be involved in PFAPA pathogenesis. Future studies with higher patient number, uninflamed tonsils and cellular markers are required to further enlighten the role of TLRs in the development of syndrome.

Association of cord blood bisphenol A (BPA) with cord blood adiponectin, leptin, fetal growth; adiposity and neoantal complications in a newborn cohort.

Objective: To evaluate the relation between cord blood bisphenol A (BPA), leptin, adiponectin, birth weight, height, skin thickness, and postnatal results.Method: This study was performed in near East University Medical Faculty, Nicosia, Cyprus with 150 healthy newborns. Cord blood leptin, adiponectin, BPA levels were measured by ELISA and birth weight, heights and back, waist, and arm skin thickness were measured and postnatal problems noted.Results: One hundred eighty-seven newborns were included in the study. Mean ± SD of BPA, adiponectin, leptin levels were 48.3 ± 2.22 ng/mL, 65.60 ± 15.29 µg/mL and 3.08 ± 2.08 ng/mL. Mean birth weight, height, head circumferences were 3156.76 ± 493.45 g, 48.28 ± 2.04 cm, 34.14 ± 1.74 cm. The association anthropometric measurements, BPA, leptin, and adiponectin levels were not statistically significant (p>.05). The relation between cord blood leptin, adiponectin, and BPA levels and small for gestation, large for gestation and average for gestation groups were not significant (p>.05). Moreover, relation between back, waist and arm skin thickness and BPA, leptin, and adiponectin were not statistically significant (p>.05). However, newborns who were hospitalized and had newborn jaundice had higher BPA levels (p<.05).Conclusion: In previous studies, higher BPA levels were associated with small for gestational age (SGA) birth, however, this relation was not noted in our study. Furthermore, there is no relation between skin thickness, BPA, leptin, and adiponectin. This difference may be as a result of higher cord BPA levels compared with previous studies.

Evaluation of Dose Dependent Maternal Exposure to Bisphenol A on Thyroid Functions in Newborns.

Bisphenol A (BPA) is an endocrine-disrupting chemical compound that is mainly used in industrial products as packaging and plastics. It usually transmits to humans via oral route from food-contact material. BPA has demonstrated to be found in body fluids with a higher amount of fetal tissues due to bio-accumulation. Although it has been reported to affect the endocrine system, results on thyroid functions of newborns are conflicting. The aim of the present study is to demonstrate the effect of different levels of BPA in cord blood on the thyroid functions of newborns, according to gender. METHODS: The study population included 88 newborns. The BPA levels, Thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels of cord blood were measured. In addition, SPINA-GT (thyroid' incretory capasity), TSH Index (TSHI), standardized TSHI (sTSHI) were calculated and demographic characteristics of participants were noted. RESULTS: The mean of cord blood BPA was 4.934 ± 2.33 ng/mL. When evaluated according to quantiles of BPA, no association was found between BPA and thyroid hormone levels, as well as, SPINA-GT, TSHI, sTSHI in both genders. CONCLUSION: Although BPA has been shown to contaminate cord blood, no significant effect was detected on thyroid hormones, SPINA-GT, TSHI and sTSHI. Further investigations with larger study populations are warranted.

Tonsillar antimicrobial peptide (AMP) expression profiles of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) patients.

INTRODUCTION: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) is the most frequent non-infectious cause of high fever observed among the European child population. While its cause is still not yet fully identified, PFAPA patients were previously shown to have altered tonsillar microbiome composition. Our study hypothesized that this is associated with a change in antimicrobial peptide (AMP) expression levels, as in the case of Crohn's disease which is another autoinflammatory disorder. METHODS AND MATERIALS: The tonsil specimens were isolated from seven patients with PFAPA syndrome, and six patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis. Tonsillar expression levels of human beta-defensin 1-2, cathelicidin, ribonuclease-7, and liver expressed antimicrobial peptide-1 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: Our results showed no significant difference in AMP expression levels between PFAPA and GAßHS patients. Immunolocalization of human beta-defensin 1 was different between the two groups; expressed at higher levels on tonsil surface epithelium (SE) than lymphoid interior (LI) in PFAPA patient group, while this was not evident in GAßHS patients group. CONCLUSIONS: Our results suggest that, PFAPA patients may be associated with altered AMP expression as in other autoinflammatory diseases. Future studies with subjects without any inflammatory condition are required for more precise conclusions.

Is celiac disease misdiagnosed in children with functional constipation?

BACKGROUND/AIMS: Functional constipation is one of the common problems in childhood, and it comprises approximately 5% of the pediatric outpatient clinical applications. On the other hand, celiac disease (CD) is an immune enteropathy with the prevalence between 1/150 and 1/200. In addition to the classical symptoms of the disease such as diarrhea and weight loss, the incidence of atypical symptoms is increasing. This study aims to determine the prevalence of CD in patients with chronic constipation. MATERIALS AND METHODS: The study was conducted between 2010 and 2012 and included 1046 children (range, 2-18 y; median, 11.4 y) diagnosed with chronic constipation according to the Rome III criteria. Serum immunoglobulin A, tissue transglutaminase, and/or anti-endomysial antibodies were examined. The patients with serological positive results were subjected to upper gastrointestinal system endoscopy and duodenal biopsy to confirm the diagnosis of CD. RESULTS: Blood tests were positive in 36 patients (3.25%). One of the patients had Hashimoto's thyroiditis, and 4 patients had short stature. Endoscopic findings included nodularity in bulbus and duodenal mucosa (n=16), scalloping fold (n=13), and normal mucosa (n=5). Histopathologic findings revealed that 10 patients had total villous atrophy, 24 patients had subtotal and partial villous atrophy, and 34 patients had intraepithelial lymphocyte infiltration. All patients followed a gluten-free diet, resulting in a resolution of symptoms. CONCLUSION: In the present study, a CD ratio of 1:28 was diagnosed in chronically constipated children. The use of screening tests for CD should be considered in children with conventional treatment-resistant constipation.

A propósito de un caso: enfermedad de Kawasaki incompleta en un niño con hipogammaglobulinemia / A case report: incomplete Kawasaki disease in a hypogammaglobulinemic child

La enfermedad de Kawasaki (EK) es una vasculitis autoinmunitaria sistémica que afecta a los vasos pequeños y medianos. La complicación principal de la enfermedad de Kawasaki es el aneurisma de las arterias coronarias, cuyo riesgo es más alto si se retrasa el diagnóstico y el tratamiento. Si bien hasta la fecha se han presentado casos de EK completa e incompleta en diferentes tipos de enfermedades por inmunodeficiencia, no se ha informado acerca de la evolución clínica de la EK en pacientes con hipogammaglobulinemia (HG). En este artículo, se presenta un caso de diagnóstico de EK incompleta en un niño con HG transitoria de la infancia. También se resumen casos previamente informados de EK e inmunodeficiencia. En el caso de una inmunodeficiencia, las infecciones recurrentes pueden ocultar la EK, lo que retrasa el diagnóstico y aumenta el riesgo de complicaciones. En pacientes inmunodeficientes, debe tenerse en cuenta la posibilidad de EK cuando la fiebre es prolongada.

Kawasaki Disease (KD) is a systemic autoimmune vasculitis that affects small and medium sized vessels. Main complication of Kawasaki Disease is coronary artery aneurism, which has higher risk in case of delayed diagnosis and treatment. Although, complete and incomplete KD cases in different types of immune deficiency diseases have been presented up to date, clinical course of KD in patients with hypogammaglobulinemia (HG) has not been reported. Herein, a case diagnosed as incomplete KD in a child with transient HG of infancy has been reported. Previously reported cases with KD and immunedeficiency have also been summarized. Recurrent infections in case of immunedeficiency may mask KD disease resulting in delay in diagnosis and increased risk of complication. KD should be kept in mind in immunedeficient patients in case of prolonged fever.

High Prenatal Exposure to Bisphenol A Reduces Anogenital Distance in Healthy Male Newborns.

OBJECTIVE: To estimate the relationship between cord blood bisphenol A (BPA) levels and anogenital measurements in healthy newborns. METHODS: Pregnancy and birth history, together with body mass and length data, anogenital measurements, penile measurements and cord blood samples were obtained from healthy newborns. Cord blood concentration of BPA was analyzed by sandwich enzyme-linked immunosorbent assays kit. RESULTS: Among 130 healthy newborns (72 boys, 58 girls), mean anopenile distance was 45.2±6 mm and anoscrotal distance was 21.9±5.4 mm in boys; mean anoclitoral distance was 33.8±6.6 mm and mean anofourchette distance was 12.2±4.9 mm in girls. Mean cord blood BPA level was 4.75±2.18 ng/mL. 90th percentile value for cord blood BPA was 8.26 ng/mL and the analysis showed a statistically significant correlation between anoscrotal distance and cord blood BPA levels above the 90th percentile (p=0.047) in boys. The changes in anogenital distance in girls were not statistically significant. CONCLUSION: We showed a significant association between high cord blood BPA levels and shortened anoscrotal distance in male newborns. However, this result should be interpreted with caution since there were no significant external genital abnormalities in our study group.

A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels.

AIM: To detect the impact of insulin-like growth factor-1 (IGF-1) and other risk factors for the early prediction of retinopathy of prematurity (ROP) and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels. METHODS: The study was conducted with 127 preterm infants. IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was analyzed. The score was established after logistic regression analysis, considering the impact of each variable on the occurrences of any stage ROP. A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated. RESULTS: Birth weights (BW), gestational weeks (GW) and the prevalence of breast milk consumption were lower, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) were more frequent, the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP (P<0.05). Initial serum IGF-1 levels tended to be lower in newborns who developed ROP. Logistic regression analysis revealed that low BW (<1250 g), presence of intraventricular hemorrhage (IVH) and formula feeding increased the risk of ROP. Afterwards, the scoring system was validated on 107 infants. The negative predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while positive predictive values were 76.3%, 65.5% and 71.6% respectively. CONCLUSION: In addition to BW <1250 g and IVH, formula consumption was detected as a risk factor for the development of ROP. Breastfeeding is important for prevention of ROP in preterm infants.

Prevalence of Mediterranean FeVer Gene Mutations in Turkish Cypriot Population.

OBJECTIVES: This study aims to determine the carrier frequency and the most common mutations of the Mediterranean FeVer (MEFV) gene in healthy Cypriot population of Turkish origin. PATIENTS AND METHODS: A total of 296 healthy participants (102 males, 194 females; median age 30 years; range 1 to 81 years) were evaluated. The exon 2, 3, 5 and 10 of MEFV genes were amplified by polymerase chain reaction. RESULTS: The participants demonstrated an extremely high carrier rate (12.5%). Most commonly detected mutations were E148Q and A74S, with rates of 7.3% and 2.8%, respectively. CONCLUSION: Mediterranean FeVer gene mutation types and carrier rates in Turkish Cypriot population are different than other Mediterranean populations in the region. MEFV mutation carriage is frequent in North Cyprus and familial Mediterranean fever might be one of the causes for end stage renal disease in Turkish Cypriots.

Prevalence of Thalassemia Trait & Iron Deficiency Anemia during Infancy in 2011-2013 in a Thalassemia Prevalent Region: North Cyprus.

BACKGROUND: Iron Deficiency Anemia (IDA) is an important health problem all around the world especially in developing countries. In the Mediterranean countries another prevelant reason of anemia is Thalassemia. Certain strategies had been established as a government policy to reduce prevalence in North Cyprus, such as pre-marital screening of Thalassemia. The prevalence of thalassemia trait has not been evaluated since then. The aim of this study was to detect the prevalence of IDA, thalassemia trait in infants under regular follow-up and to evaluate the compliance to prophylactic iron supplementation (PIS) and its effect on IDA. METHODS: Healthy children admitted to Department of Pediatrics, Near East University Hospital, in 2011-2013 were included. Data of anthropometric measurements, parental thalassemia trait status, duration of PIS usage, complete blood count, ferritin levels and hemoglobin electrophoresis were collected from hospital database program. Anemic children were grouped as IDA, thalassemia trait, both IDA and thalassemia trait and others. RESULTS: Eighty-nine infants with a mean age 13.52±2.09 mo were included. Compliance with PIS recommendation was 85.3% and, the mean duration of iron usage was 6.44±3.18 mo. IDA and thalassemia trait were found to be 11.2% and 4.5% respectively, while 3.4% of the infants had both IDA and thalassemia trait. CONCLUSION: Prevalence of thalassemia trait was 7.9% demonstrating approximately a 50% decline within 5 decades. This result confirms the success of premarital screening policy in North Cyprus. In addition, prevalence of IDA was relatively low being 14.6% supporting the beneficial effect of PIS on prevention of IDA.

Leptin, ghrelin and calprotectin: inflammatory markers in childhood asthma?

BACKGROUND: Appetite-modulating hormones ghrelin and leptin might be relevant to asthma with their pro-inflammatory effects, and calprotectin has been recognized as a promising marker of inflammation. The purpose of this study was to explore whether asthma, atopy and lung functions has a relation with serum levels of leptin, ghrelin and calprotectin as inflammatory markers in children. METHODS: A cross-sectional study was performed by searching the doctor diagnosed asthma through questionnaires filled in by parents who were phoned, and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to perform skin prick test and spirometry. Participants were divided into Group 1, children with previous diagnosis of asthma, and Group 2, children without previous diagnosis of asthma. RESULTS: One thousand and two hundred questionnaires were distributed and 589 of them were returned filled in. Out of 74 children whose parents accepted to participate in the study, 23 were in Group 1 and 51 were in Group 2. There was no statistical difference in serum levels of leptin, ghrelin, calprotectin, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) , forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) values , and skin prick test results between the two groups (p values are 0.39, 0.72, 0.5, 0.17, 0.5, 0.27, 0.18, and 0.81 respectively). CONCLUSION: In this study the inflammation in asthmatic children could not be shown by using serum leptin, ghrelin and calprotectin levels and this is possibly due to the low number of children with ever asthma and equal skin prick test positivity in both groups. This study is the first study aimed to show the relation between serum calprotectin levels and inflammation in asthma. As this study was a cross-sectional study, further prospectively designed randomized controlled studies are necessary to show the association of these markers and inflammation in asthma.

Rosai-Dorfman disease presenting as mediastinal lymphadenopathy: case report and review of the literature.

A 6-year-old boy presented with recurrent pneumonia and diarrhoea for 3 years. He had extensive mediastinal lymphadenopathy and atelectasis with low serum levels of IgA, IgG and IgG3. An inguinal lymph node biopsy demonstrated histological and histochemical features of Rosai-Dorfman disease. There was emperipolesis and histiocytes were immune-positive for S100 proteins. He responded to corticosteroids and regular infusions of immunoglobulins.

Is calprotectin a marker of tobacco smoke related inflammation?: a pilot study in children.

CONTEXT: Environmental tobacco smoke (ETS) related inflammation has an anorexigenic effect through affecting the release of appetite-modulating mediators, leptin and ghrelin. Elevated serum calprotectin levels are found in a variety of inflammatory conditions. OBJECTIVE: To study the relation between ETS and body mass index (BMI), as well as serum levels of leptin, ghrelin and calprotectin. MATERIALS AND METHODS: A cross-sectional study was performed by searching the smoking status of parents. After filling in the questionnaires, parents were phoned and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to calculate their BMIs. Participant children were divided into Group 1 (n = 51), those who are not exposed to and Group 2 (n = 46), exposed to indoor ETS. RESULTS: There were no statistical difference in BMI, leptin and ghrelin levels between Group 1 and Group 2 (p values are 0.85, 0.87 and 0.42, respectively), but serum calprotectin levels were statistically higher in Group 2 (p = 0.003). DISCUSSION AND CONCLUSION: In this study serum levels of calprotectin were found to be higher in children with indoor ETS exposure where no relation was detected with BMI and serum levels of leptin and ghrelin. Increased serum levels of calprotectin might be an indicator of inflammation related to ETS exposure.