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Introduction: Around 40% of infants with bronchiolitis will present recurrent wheezing in the first years of life. It is still unclear whether the virus directly modifies the host immune response or it infects infants somehow prone to wheeze. Aim: To evaluate whether Respiratory Syncytial Virus(RSV)-RNA load and IFN lambda 1-3 expression correlate with wheezing 36 months after bronchiolitis. Methods: We reviewed 68 (43 males, age range: 7-277 days) infants hospitalised for RSV bronchiolitis at the Paediatric Emergency Department, “Sapienza” University of Rome. Nasopharyngeal washing was collected from each infant, and divided into two aliquots (one for nucleic acid extraction and viral detection, the second for gene expression analysis). A TaqMan-based real-time PCR technique for RSV RNA quantification was performed. The mRNA copy content of IFN lambda 1, and 2/3 was measured by a real-time 59 exonuclease RT-PCR assay using the Light Cycler 480 sequence detector. 12-24-36 months after discharge, one of the authors interviewed parents of all infants using a standardized telephone procedure with a structured questionnaire seeking information on recurrent wheezing. Results: 29/68 (42.6%) infants with bronchiolitis experienced recurrent wheezing at 36 months follow-up. Children with recurrent wheezing after bronchiolitis showed a significantly higher RSV-RNA load(p=0.015) and higher IFN lambda 2/3 levels than wheezing negative patients(p=0.047). Conclusions: A high RSV-RNA load and IFN lambda activation at the admission for bronchiolitis are associated with recurrent wheezing after 36 months. We could speculate that this viral-related inflammation might cause bronchial lumen modifications.

Coeliac disease (CD) is a chronic, gluten-dependent enteropathy with a prevalence of approximately 1% in Western countries. Up to now, CD has been described only in sporadic cases of obesity. Our study aimed to evaluate retrospectively CD prevalence in a large series of overweight/obese children and adolescents. Among the 1527 overweight/obese children and adolescents consecutively evaluated, 17 (7 boys, 1.11%) were positive for serology and showed villous atrophy. In all of the patients with CD a well-balanced gluten-free diet was started, and a loss of weight rapidly obtained. Our study demonstrates that CD prevalence in overweight/obese children is similar to the general paediatric population in Italy.

A highly sensitive electrochemical immunoassay for the initial diagnosis of celiac disease (CD) in saliva samples that overcomes the problems related to its high viscosity and to the low concentration of anti-transglutaminase antigen (tTG) IgA in this medium has been developed for the first time. The system uses magnetic beads (MBs) covered with tTG, which reacts with the anti-tTG IgA antibodies present in positive saliva samples. An anti-human IgA, conjugated with alkaline phosphate (AP) enzyme, was used as the label and a strip of eight magnetized screen-printed electrodes as the electrochemical transducer. In particular, two different immunoassay approaches were optimized and blindly compared to analyze a large number of saliva samples, whose anti-tTG IgA levels were independently determined by the radioimmunoassay (RIA) method. The obtained results, expressed as Ab index, were used to perform a diagnostic test evaluation through the construction of receiver operating characteristic (ROC) curves. The approach, involving a pre-incubation between the anti-human IgA-AP and saliva samples prior to the addition of MBs-tTG, showed a cutoff of 0.022 with 95 % clinical sensitivity and 96 % clinical specificity. The area under the ROC curve is equal to 1, a result that classifies our test as “perfect.” This study demonstrates that it is possible to perform the screening of CD with a rapid, simple, inexpensive, and sensitive method able to detect anti-tTG antibodies in saliva samples, which are easily obtained by non-invasive techniques. This aspect is of fundamental importance to screen a large number of subjects, especially in the pediatric age.

Celiac disease (CD) is a gluten-dependent autoimmune enteropathy which occurs in genetically predisposed individuals. CD can manifest in a typical form (with gastrointestinal symptoms), with an atypical form (iron-deficiency anemia, headache, recurrent aphthous stomatitis) or be asymptomatic (silent form). Over the last decades CD prevalence increased (1.2%), mainly due to the improvement and diffusion of screening tools such as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies. The authors report a case of a 39 months old IgA deficiency girl with a severe abdominal distention and iron deficiency anemia, negative for CD-related antibodies, who was diagnosed celiac. Surprisingly, after six months of gluten-free diet, the patient showed the appearance of IgG class – CD specific antibodies.

Objectives Patchy villous atrophy of the duodenal mucosa has been described in adults with untreated celiac disease (CD) but not in children. The authors evaluated the presence and the distribution of villous atrophy in children with celiac disease to see whether this histologic pattern exists in children. Methods We studied 95 children at diagnosis (Group 1) and seven during gluten challenge (Group 2). We measured anti-endomysium antibodies (EMA) by immunofluorescence on monkey esophagus, antihuman-tissue transglutaminase autoantibodies (anti-tTG Abs) by radioimmunoprecipitation, and HLA-DQ2/DQ8 heterodimers by polymerase chain reaction using specific primers. During upper intestinal endoscopy, at least five duodenal biopsy samples were obtained, one from the duodenal bulb and four from the distal duodenum. Results Thirteen of 95 (13.7%) patients in Group 1 and in 3 of 7 (42.9%) in Group 2 had patchy villous atrophy of the duodenum. In all 16 patients, villous atrophy of the bulb was present. In four children from Group 1, villous atrophy was observed only in the bulb samples. EMA, anti-tTG Abs, and HLA-DQ2/DQ8 heterodimers were present in all patients. Fourteen of 16 had symptomatic CD, and two were silent, detected during screening in subjects at risk for CD. Conclusions This is the first study demonstrating that children with CD may have patchy villous atrophy of the duodenum. The bulb mucosa may be the only duodenal area involved, both at diagnosis and after gluten challenge. Therefore, multiple endoscopic biopsies should always be performed, not only in the distal duodenum, but also in the bulb.

OBJECTIVE To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis. RESEARCH DESIGN AND METHODS IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb+ DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis. RESULTS A total of 12.8% DM1 sera were IgA-tTGAb+, with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb+ DM1 compared with nondiabetic CD patients. CONCLUSIONS Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis.

Rhinovirus and interferon-λ: missing pieces of the puzzle of childhood asthma http://ow.ly/vBL9308zN20

Bronchoalveolar lavage (BAL) is a diagnostic procedure used for recovering cellular and non-cellular components of the epithelial lining fluid of the alveolar and bronchial airspaces. Non-bronchoscopic BAL involves the insertion of simple catheters or balloon-type devices through an endotracheal tube, while bronchoscopic BAL involves the instillation and immediate withdrawal of pre-warmed sterile 0.9 % saline solution through the working channel of a flexible bronchoscope, preferably in the middle lobe or the lingula. The parameters measured in BAL fluid (BALF) include the percentage of the instilled normal saline that is recovered as well as various BALF cellular and non-cellular components. BAL is performed for diagnostic, therapeutic, and research purposes. The most important indication for BAL in children is in the work up of infectious diseases. Other indications for BAL include non-specific chronic respiratory symptoms, non-specific radiological findings, and clinical symptoms suggestive of interstitial lung disease. BAL is still considered to be the gold standard for diagnosing chronic pulmonary aspiration. BAL is a well-tolerated and safe procedure; however, on occasion, fever, cough, transient wheezing, and pulmonary infiltrates have been observed, which usually resolve within 24 h.

Background: Several studies showed an involvement of the gastric mucosa in celiac disease (CD). Helicobacter pylori (Hp) is the major agent of gastric damage. The aim of this article was to present a literature review of a possible correlation between the two conditions. Methods: A literature search was conducted in Medline, Scopus and Directory of Open Access Journal (DOAJ) using appropriate keywords. We included only articles written in English over the period July 1996 - May 2014. Results: The search for Medline, Scopus and DOAJ provided a total of 530 citation. Twenty five studies met the inclusion criteria and were included in quantitative analysis. The prevalence of Hp infection in celiac children and adults from different geographical areas has been reported. The possible correlation between Hp infection and the increase of intraepithelial lymphocytes (IEL) has also been reported. Conclusion: Several studies showed a wide heterogeneity. This is probably due to differences in Hp prevalence, small series of patients, lack of histological confirmation of Hp and lack of adjustment for sociodemographic characteristics. More studies to clarify the possible correlation between these two conditions are necessary.

The relationship between viral infection, host immune response in infants with respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing is discussed. We measured RSV-RNA load and interferon-λ1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for RSV bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. Higher RSV-RNA load and higher interferon-λ2/3 levels were found in children with recurrent wheezing at 36-month follow-up.

To assess the frequency of celiac-associated humoral autoimmunity in patients with long-standing childhood- and adult-onset type 1 diabetes (LDM1) and whether it occurs more frequently as the disease progresses. IgA-/IgG-anti-tissue transglutaminase (IgA-tTG and IgG-tTG) and IgA-/IgG-deamidated gliadin (DGP) antibodies were analyzed in 277 LDM1 sera (120 females; disease duration 19.3 ± 12.3 years, range 5.0-54.0 years). Of the 277 patients, 147 were childhood-onset LDM1 ((CH)LDM1) and 130 adult-onset LDM1 ((AD)LDM1); 6.1 % LDM1 sera were tTG- and/or DGP-antibody-positive, with a lower frequency among (CH)LDM1 as compared with (AD)LDM1 patients (3.4 vs 9.2 %, p = 0.048). Celiac-associated immunoreactivity was significantly more frequent in LDM1 with15 years of disease duration (9.4 vs 2.9 % in those with ≤15 years, p = 0.042) and among them in (AD)LDM1 (14.7 vs 4.2 % (CH)LDM1, p = 0.043). Celiac disease humoral immunoreactivity should be screened not only at diabetes onset, but also in long-standing patients, especially adults with disease duration15 years.

Background Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. Methods In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. Results Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm3, p 3, p B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. Conclusions When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.

Objective: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy. Identifying CD in schoolchildren to characterize CD iceberg and evaluate the effect of diagnosis in screening-detected children. Methods: A total of 7377 5- to 8-year-old children were invited to participate. A total of 5733 salivary samples were collected and tested for anti-transglutaminase antibodies (tTGAb), using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy and then started gluten-free diet (GFD) and periodical follow-up. Results: Forty-six subjects were found salivary tTGAb‐positive and 16 border-line. Forty-five of 46 and 5 of 15 of them were also serum antibody‐positive. Forty-two children showed duodenal villous atrophy and 1 had only type 1 lesions. Three children started GFD without performing endoscopy.CD prevalence(including23 previously diagnosedchildrenwith CD) was 1.2%. Considering all 65 celiacs in our sample, a silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%. All patients showed strict adherence to GFD, weight and stature increase, and well-being improvement. Eighty-five percent and all but 2 screeningdetected children with CD had Italian parents. Conclusions: Our sample size, representative of primary schoolchildren of our region, demonstrated that CD prevalence is growing in Italy, with a modified clinical spectrum and iceberg deepness.

Objectives: Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC). Methods: In a retrospective study on 226 patients with CD (82M; median age: 5.7years) at diagnosis and 154 GC (66M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti-gastric parietal cell antibodies (GPCA) were assayed by enzyme-linked immunosorbent assay. Results: A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) childrenwithGC(91.7%hadCSG).AmongpatientswithCSG,Hpinfection was more frequent in controls than in celiac children (P

Mucosal interleukin (IL)-17A-producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ-producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL. The physiological age-dependent increase of Th17 IEL is also absent in CD, while IFN-γ-producing PB-T cells significantly accumulate with patient's age. Finally, the amplitude of IL-17A+ and IFN-γ+ T-cell pools are significantly correlated in different individuals; this relationship only applies to CD4+ T cells in controls, while it involves also the CD4- counterpart in CD patients. In conclusion, both size and dynamics of mucosa-associated and circulating IL-17A+ T-cell pools are finely regulated in human pediatric subjects, and severely disturbed in CD. The impaired IL-17A+ IEL-T pool may negatively impact on epithelial barrier efficiency, and contribute to CD mucosa damage; the disturbed dynamics of circulating IL-17A+ and IFN-γ+ T-cell pools may be involved in the extraintestinal autoimmune manifestations associated with CD.

From the authors: We thank M. Korppi and co-workers for their correspondence regarding our article [1]. In our prospective study, we identified rhinovirus (RV) infection and a positive family history for asthma as substantial risk factors for recurrent wheezing during 1-yr follow-up after the initial episode of bronchiolitis. The distinctive point of our study was that all the infants enrolled had clinically well-characterised bronchiolitis, defined as the first episode of acute lower airway infection that appears with a history of upper respiratory tract infection followed by acute onset respiratory distress with cough, tachypnoea, retraction and diffuse crackles on auscultation in infants

BACKGROUND Celiac disease (CD)-related lesions were described in duodenal bulb of celiac patients. GOAL Our aim was to evaluate the morphology of bulb mucosa in adult celiac patients and in controls to evaluate its usefulness for CD diagnosis. STUDY We studied 43 celiac patients (10 male, median age: 35.2 y) at diagnosis and 43 gastroenterological controls (10 male, median age: 37.8 y), submitted to upper endoscopy for gastroenterological complaints. Histologic lesions were assayed by an experienced pathologist according to the Marsh modified classification. Antiendomysium antibodies and antitransglutaminase antibodies-tTGAb (ELISA and/or RIA) have been tested. In selected patients, DNA was typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer polymerase chain reaction. RESULTS In all celiac patients lesions were present in the bulb mucosa. One female with thyroiditis, who had a CD daughter, showed lesions only in the duodenal bulb. Patchy villous atrophy was found in another patient. All celiacs were antiendomysium and/or tTGAb positive. DQ2 heterodimer was present in 5 CD patients. The gastroenterological controls showed normal mucosa in the duodenum. CONCLUSIONS This study demonstrates that CD-related histologic lesions are present in duodenal bulb of adult patients. Moreover, the normal aspect of this mucosa in gastroenterological controls implies the high negative predictive value of this finding. Therefore, we suggest taking at least 1 biopsy on the bulb area and 1 from the distal duodenum for CD diagnosis, in all the patients submitted to upper endoscopy, to avoid missed or delayed diagnosis.

The high prevalence of celiac disease (CD) prompted us to evaluate a new, noninvasive disease screening strategy. The aim was to identify CD in 6- to 8-year-old children for a timely diagnosis, start gluten-free diet (GFD) in compliant subjects, achieve the growth target, and prevent CD complications.Five thousand subjects were invited to participate in the study. Four thousand forty-eight saliva samples were tested for anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A using a fluid-phase radioimmunoprecipitation method. Positive children were tested for serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children confirmed as positive by serum assays underwent endoscopy with duodenal biopsies and, at the diagnosis of CD, were suggested to start GFD.Consent was obtained from 4242 parents (84.8%) for the screening to be performed, and adequate saliva samples were collected from 4048 children (95.4%). Thirty-two children were found to be salivary tTG IgA positive and 9 with borderline autoantibody levels. Thirty-one of the 32 and 3 of the 9 subjects were also serum positive. Twenty-eight children showed villous atrophy when undergoing intestinal biopsy, whereas 1 had Marsh 1 lesions; 3 children were suggested to start GFD without performing endoscopy. CD prevalence in the population investigated (including 19 CD known cases) was 1.16%. The ratio between screening-detected patients and those diagnosed before the screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6.We demonstrated that it is possible to perform a powerful, simple, well-accepted, and sensitive CD screening using saliva. Until now, the compliance with GFD in children with CD has been optimal.

We describe a previously healthy 12-year-old boy who attended our Department after a sudden episode of hemoptysis and recurrent consolidation. CT-scan revealed a mediastinal tumor. The biopsy specimens taken from the mass showed a mature teratoma. Hemoptysis is an unusual presenting symptom in an otherwise healthy child with a well capsulated, unruptured mature mediastinal teratoma. In this report, hemoptysis prompted us to undertake the diagnostic work-up that eventually disclosed the tumor. Pediatr. Pulmonol. 2011; 46:1146–1148. © 2011 Wiley Periodicals, Inc.

Bronchoalveolar lavage (BAL) is a diagnostic procedure used to recover cellular and non-cellular components of the epithelial lining fluid from the alveolar and bronchial airspaces. Two types of the procedure have been described: bronchoscopic and non-bronchoscopic BAL. The preferred site for bronchoscopic BAL is the middle lobe or the lingula. Gentle manual or mechanical aspiration is applied in order to collect the lavage specimen in the collection trap, while the tip of the flexible bronchoscope is maintained wedged in the bronchus of the selected lavage site. The parameters measured in BAL fluid (BALF) include the percentage of the instilled normal saline that is recovered as well as various BALF cellular and non-cellular components. BAL is performed for diagnostic, therapeutic and research purposes. The most common indication for BAL is the investigation of lower respiratory tract infection. In chronic interstitial lung disease, BAL may have an important role in reaching a specific diagnosis, characterizing alveolitis, and monitoring patients during treatment and follow-up. BAL is still considered the gold standard for diagnosing chronic pulmonary aspiration. In general, BAL is a well-tolerated and safe procedure; however, on occasion, cough, transient wheezing and pulmonary infiltrates have been observed, which usually resolve within 24 h.

Celiac disease (CD) is a rare example of multifactorial disorder in which a genetic test is of great clinical relevance, as the disease rarely develops in the absence of specific HLA alleles. We typed DR-DQ genes in 437 Italian children with celiac disease, 834 first-degree relatives, and 551 controls. Of patients, 91% carried DQ2 and/or DQ8 heterodimers, 6% only had beta2 chain, 2% was alpha5 positive, and four were DQ2/DQ8/beta2/alpha5 negative. Only the presence of alpha5 resulted negatively associated to disease (p = 2 x 10(-4)), whereas we confirmed the effect of the beta half of DQ2 dimer on CD predisposition (p = 4 x 10(-12)). Considering 1:100 disease prevalence, we obtained a risk gradient ranging from 1:7 for DQ2 and DQ8 individuals down to 1:2518 for subjects lacking all predisposing factors. The DQB1*02 and DQB1*0302 concurrence (p = 9 x 10(-4)), besides the DQB1*02/*02 homozygosity, had an additional role in disease genetic determination. The CD prevalence rose to 17.6% in sisters, 10.8% in brothers, and 3.4% in parents. In the three groups, the subjects carrying high-risk HLA molecules were 57%, 71%, and 58%; among them, 29%, 15%, and 6% respectively had CD. Those siblings and parents with no susceptible factors were not affected. These findings indicate the impact of the HLA test for CD in clinical practice.

Objectives: Celiac disease is an autoimmune enteropathy caused by gluten ingestion in genetically susceptible individuals. Anti-transglutaminase autoantibody (tTGAb) assay is useful to detect candidates undergoing intestinal biopsy. Our aim was to investigate whether the DQB1*02 allele could influence tTGAb titers and the clinicopathological expressivity of the disease. Methods: A total of 124 patients with celiac disease, tested for RIA tTGAb at diagnosis, were typed for HLA-DRB 1, -DQA 1, and -DQB1 genes and divided according to the number of DQB1*02 alleles: group 1, homozygous; group 2, heterozygous; group 3, negative. Results: The mean of tTGAb indexes was significantly higher in group 1 patients than in group 2 (P < 0.02) and group 3 patients (P

Background Celiac disease (CD) is a complex disorder triggered by gluten affecting genetically predisposed individuals. More than 90% of patients carry human lymphocyte antigen (HLA)-DQ2 (DQA1*05, DQB1*02) and/or HLA-DQ8 (DQA1*03, DQB1*0302). We propose the use of the DQ-CD Typing kit that allows identification of the HLA class II alleles (DQA1*0201,*03,*05, DQB1*02,*0302, DRB1*03,*04,*07) selected to be informative in the CD risk evaluation and of a second kit, namely DQ-CD Zygosis, for DQB1*02 homozygosity determination. Methods The study was performed on a cohort of 100 individuals previously HLA typed with commercial kits. Fresh blood or previously extracted DNA was amplified in a unique PCR program using allele-specific primers and visualized on agarose gel. Results DNA amplification yielded strong and clear products without non specific signals or ghost bands. All the samples showed the expected alleles in accordance with the previous HLA typing. Conclusions The DQ-CD Typing and Zygosis kits are fast, simple, economical and accurate tools that can be used to determinate the HLA-DQ2/DQ8 status in laboratory practice addressed for the diagnosis of CD. Molecular HLA testing is considered a valid support in the confirmation/exclusion of CD, especially in high-risk groups, such as CD relatives, or when serological and histological data are ambiguous.

C.M. Trovato1,∗, M. Montuori1, F. Valitutti 1, P. De Luca1, L. Pezza1, C. Tiberti 3, D. Iorfida1, F. Lucantoni3, R. Nenna2, M. Mennini1, C. Anania1, M. Bonamico2, S. Cucchiara1 1 U.O.C. di Gastroenterologia ed Epatologia Pediatrica, Dip. di Pediatria e Neuropsichiatria Infantile, Sapienza Universita di Roma, Italy 2 Dip. di Pediatria e Neuropsichiatria Infantile, Sapienza Universita di Roma, Italy 3 Dip. di Medicina Sperimentale, Sapienza Universita di Roma, Italy

The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy.We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy.TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up.On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.

The aim of the present study was to evaluate the epitope specific humoral human tissue transglutaminase (tTG) immunoreactivity against 3 different human recombinant tTG constructs [(full-length tTG (a.a. 1–687), tTG (a.a. 227–687); tTG (a.a. 473–687)] before and after the introduction of a gluten-free diet (GFD). To this end, sera from 64 celiac disease (CD) subjects on a gluten-containing diet (44 f, 20 m) and after 0.6 ± 0.3 years and 2.1 ± 1.3 years of GFD were studied using a quantitative radioimmunoprecipitation assay. All 64 CD patients at diagnosis were full-length anti-tTG (a.a. 1–687)Ab positive. These Abs significantly decreased in frequency and titer after 6 months and 2 years of GFD. However, at low titers, 64.1% (41/64) of CD patients were still fl-tTG (a.a. 1–687)Ab positive after 2 years of GFD. At disease diagnosis, 70.3% (45/64) of the CD patients had Abs directed against fragments (227–687) and/or (473–687) of the tTG protein. This percentage, after 2 years of GFD, significantly decreased to 18.7%, whereas almost 50% of GFD patients had no tTG (227–687) and tTG (473–687) fragment reactivity, but only persistent, low-titer full-length tTG (1–687)Abs. We suggest that the selective loss of immunoreactivity against tTG (227–687) and tTG (473–687) fragments in CD patients with a GFD, could be due to quantitative decrease of autoreactivity driven by tTG-gliadin interaction underlying celiac disease pathogenesis.

Objective: Antiendomysial antibody (EMA) production has been induced in vitro by the small bowel mucosa of celiac disease (CD) patients in clinical remission cultured in the presence of gliadin peptides. The aim of the present study was to use this in vitro system to determine whether it could be used to predict the clinical or histologic relapse to gluten challenge in CD children on a gluten-free diet (GFD). Methods: Enrolled were 32 CD children and adolescents on GFD (group 1), and 80 controls (group 2) who underwent in vitro gliadin challenge. Subsequently, 24 group 1 CD children underwent in vivo gluten challenge to confirm the diagnosis. Biopsy cultures, with and without gliadin, morphometric analysis, immunoglobulin (Ig)A and IgG1 EMA detection, both in sera and culture supernatants, were performed. Results: Of the 32 group 1 CD patients, 23 were IgA EMA positive in culture supernatants. The other nine were IgG1 EMA positive. All 24 children who had in vivo gluten challenge showed clinical or histologic relapse. All culture supernatants from disease controls belonging to group 2 were both IgA and IgG1 EMA negative, irrespective of gliadin challenge. Conclusions: Organ culture with in vitro gliadin challenge is able to reproduce the results of in vivo challenge. This system could reduce the need for gluten challenge in celiac children.

Objective To test the possibility of detecting tissue transglutaminase autoantibodies (tTG-Abs) in saliva with a novel sensitive fluid-phase radioimmunoassay (RIA). Study design Paired saliva and serum samples from 39 patients with celiac disease (CD), at the first biopsy (Group 1: 28 females, mean age 11.5 ± 11.1 years); 32 controls with a normal duodenal mucosa (Group 2: 18 females, mean age 8.1 ± 3.6 years); and 32 healthy volunteers (Group 3: 21 females, mean age 31.7 ± 9.8 years) were studied for tTG-Ab presence. Limit of positivity for salivary assay was calculated according to the 99th percentiles of Group 2 control children and was expressed as an autoantibody (Ab) index. Results Salivary tTG-Abs were found in 97.4% of the patients with CD and in 100% of the corresponding serum samples. All Group 3 subjects were negative with both saliva and serum assays. A correlation between saliva and serum tTG-Ab titers was found (r = 0.826, P = .0014). Conclusions This study demonstrates that it is possible to detect salivary tTG-Abs in CD with a non-invasive, simple to perform, reproducible and sensitive method.

Background. Endoscopy represents the gold standard for the diagnosis of Helicobacter pylori infection. We evaluated three noninvasive tests in a group of children: the immunoassay for detection of H. pylori stool antigen, the polimerase chain reaction for identification of bacterial DNA on the oral cavity and the serum specific antibodies. Materials and Methods. One hundred and ninety children underwent endoscopy for various gastrointestinal symptoms. H. pylori stool antigen and anti-H. pylori antibodies were assayed by commercial kits. The bacterial DNA on saliva and oral plaque was detected by a seminested PCR. Results. Based on the positivity of culture or urease rapid test and histology, infection was detected in 47 patients. The statistical analysis showed that, for the detection of the infection, stool antigen assay is more effective in sensitivity and negative predictive value (91.5% and 96.5%), whereas specificity and positive predictive values appear slightly better in serology (89.6% and 76.0%). Correlations between serum IgG both with patients’ age (r = 0.21, p

Our aim was to evaluate body composition in a group of coeliac disease adolescents on a gluten-free diet and to re-examine them at the end of the adolescence spurt. We studied 48 patients (group 1A), 30 age-matched healthy controls (group 2A), 11 group 1A patients after 4 years (group 1B) and 11 adolescents who were age- and sex-matched with group 1B (group 2B). Weight, height, bone mineral content, fat mass, fat-free mass (FFM) and bone mineral density were evaluated using dual-energy X-ray absorptiometry. All parameters were lower in group 1A than in group 2A subjects ( p

The prevalence of dyspepsia is up to 40% in population-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by defecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastrointestinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individuals with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic techniques, such as "water immersion" and confocal endomicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically significant way. However this assumption should be confirmed further larger studies.

In a recent paper in Gut , describing a Swedish population-based cohort, Zugna et al found that women with coeliac disease had normal fertility, but their fertility had decreased in the 2 years preceding the diagnosis of coeliac disease.1 This study provides important answers to fertility problems in patients with coeliac disease by analysing a nationwide database. The results, however, must be interpreted with caution. This paper may be considered confusing because the role of coeliac disease as one of the causes of infertility has been underestimated taking into account population studies in general. Infertility, spontaneous abortion and delayed puberty represent subclinical coeliac disease presentations …

Objectives: Lymphocytic gastritis (LG) has been described in coeliac disease (CD) patients and in patients with Helicobacter pylori (Hp) infection but the pathogenetic mechanism remains unknown. Aims: The aim of our study was to evaluate the characteristics of the gastric mucosa and the prevalence of lymphocytic gastritis in a large series of CD children and adolescents. Methods: 167 CD children at the diagnosis (F 108; range 11 months–18 years), consecutive performing the upper-intestinal endoscopy at our Department over the period Jan 2008-Dec 2009, were enrolled. Duodenal (2 bulb and 4 distal duodenum samples) together with gastric antral biopsies, were performed. CD diagnosis was performed according to the NASPGHAN criteria. Hp infection was diagnosed by histology and the rapid urease test. Gastric lesions and duodenal biopsies were classified according to the modified Updated Sydney System and to the modified Marsh classification, respectively. Anthropometric and clinical data of each patient were registered at the diagnosis. Moreover, gastric parietal cells antibodies (APCA) were determined with an ELISA. Results: Gastric alterations was found in 38/167 CD children (23%). Particularly, lymphocytic gastritis was found in 13 CD patients (7.8%); superficial chronic gastritis (SCG) was detected in 24 celiacs (14.4%); and one child (0.6%) showed severe interstitial chronic gastritis (ICG). 3/38 children (one with LG, one with SCG and one with ICG) presented Hp infection. Ten patients with LG were symptomatic (7 typical and 3 atypical) while four were silent. Among patients with SCG, 16 children were typical, 5 atypical and 3 silent, and the prevalent symptoms were diarrhoea, abdominal pain and low weight growth. In the table are shown histological grading of the gastric mucosa in LG and SCG patients. The most frequent duodenal lesion, total villous atrophy (Marsh 3C), was detected in 100% and 92% of LG and SCG CD patients. Among CD children, no APCA were found in patients without gastritis, while 3/22 with gastric lesions were positive for APCA (one with mild LG and the other two with mild SCG).