Martina Filippelli

Helicobacter pylori infection and atopic diseases: Is there a relationship? A systematic review and meta-analysis

AIM To review and conduct a meta-analysis of the existing literature on the relationship between Helicobacter pylori (H. pylori), atopy and allergic diseases. METHODS Studies published in English assessing the prevalence of atopy and/or allergic diseases in patients with H. pylori infection and the prevalence of H. pylori infection in patients with atopy and/or allergic diseases were identified through a MEDLINE search (1950-2014). Random-effect model was used for the meta-analysis. RESULTS Pooled results of case-control studies showed a significant inverse association of H. pylori infection with atopy/allergic disease or with exclusively atopy, but not with allergic disease, whereas pooled results of cross-sectional studies showed only a significant association between allergic disease and H. pylori infection. CONCLUSION There is some evidence of an inverse association between atopy/allergic diseases and H. pylori infection, although further studied are needed.

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis.

AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.

Extending the Debate on Poor Response to Hepatitis B Virus Vaccination in Children With Celiac Disease: Which Question Remains?

Dear Editor, A poorer response to hepatitis B vaccination, in coeliac subjects, compared to healthy subjects, has been largely debated. Almost all authors postulated that human leukocyte antigen (HLA) genotype DQ2, found in 90 - 95% of coeliac patients, could represent the main cause in determining the impaired antibody response to recombinant HBV vaccine (1), as well as observed also in healthy not responder subjects. However it has been supposed that gluten intake could represent the main factor in influencing a poorer response to vaccine, since in several studies, it has been observed that the percentage of responders in patients compliant with a gluten free diet (GFD) was similar to healthy subjects (2, 3). Since type I diabetes (T1DM) and coeliac disease (CD) have the same genetic background, given by the HLA molecules that have also been identified as haplotypes associated with unresponsiveness to hepatitis B virus (HBV) vaccination (DR3 and DR4 for T1DM, DQ2 and DQ8 for CD), we firstly compared three different groups of patients, corresponding to T1DM, CD and DMT1-CD, that had in common the same HLA haplotypes, to establish the weight of specific haplotypes of HLA and/or gluten that could favor a poorer response to HBV vaccine. In 30 children suffering from both CD and DMT1, vaccinated by the administration of three doses of vaccine (Engerix-B, Glaxo Smith Kline, London, United Kingdome) at the age of 3, 5 and 11 months of life, according to the national vaccination schedule, we discovered 16 (53.3%) non-responders. This percentage was similar to a previous study on 60 coeliac patients (4), although not significantly higher, compared to a previous study on 100 diabetics (5) (Table 1). Table 1. Characteristics of Patients With Type 1 Diabetes Mellitus, Celiac Disease and Associated Type 1 Diabetes Mellitus/Coeliac Disease a As the mean age and the anti-HBs antibodies titers was similar between coeliacs and coeliacs/diabetics, we consider that the presence of T1DM and its HLA haplotype seems to not decrease anti-HBs antibodies production and percentage of responders. The open question is: what is the role of gluten in this matter? Comparing the T1DM/CD and T1DM, in which both groups had a similar HLA haplotype, we found a higher non-significant percentage of non-responders in T1DM/CD than in T1DM (53.3% vs. 38.2%), although the first group even had a significantly lower mean age (P < 0.0001), which usually is associated to a higher titer of anti HBs antibodies (P < 0.02) and a higher percentage of responders, as we also found in our study (Table 1). The question still remains open: what is the role of gluten in this matter? First of all, we observed that the percentage of non-responders is higher in T1DM/CD patients, compared with diabetics (53.3% vs. 38.2%). However, if we compare the first group with coeliacs, the percentage of non-responders is similar (53.3% vs. 50%). As the genetic substrate of HLA haplotypes, in the two diseases, is the same, this comparison indirectly confirms that gluten certainly represents a second variable, which favors a further decrease of efficacy to HBV vaccine, beyond the HLA system. As written in 1890 by in the chapter “The Science of Deduction” of the book “The Sign of Four, eliminate all other factors and the one which remains must be the truth (6).”

Allergen immunotherapy, routes of administration and cytokine networks: an update.

Allergen immunotherapy is a disease-modifying therapy, effective for the treatment of allergic rhinitis, allergic asthma, conjunctivitis or stinging insect allergy. Allergen immunotherapy involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response. Although precise underlying mechanisms of the induction of immune tolerance remain unclear, immunotherapy has been associated with the induction of distinct subsets of Tregs that eventually lead to peripheral tolerance by inducing a deviation from Th2 to Th1 immune responses. This review focuses on the current knowledge of the mechanisms of immunotherapy in relationship to different routes of administration and also provides a unifying view.

New approaches in hepatitis B vaccination for celiac disease

Celiac disease (CD) is a gluten-induced immune-mediated disorder that has been associated with a defective response to the hepatitis B virus (HBV) vaccination. This unresponsiveness could lead to a world health problem, because non-responder patients could represent a reservoir of HBV-susceptible people that will persist as healthy carriers, leading to the diffusion of the disease. This article presents a literature review of both intramuscular (IM) and intradermal (ID) routes for boosters in celiac patients. We used PubMed database and generated the odds ratio (OR) of the response on the basis of electronic searches of clinical trials. Although our results confirm the positive response of celiac patients to IM vaccination, the ID route seems to be better than the conventional one, since it could provide a saving in cost and a greater immunogenicity.

New available biomarkers to face a worldwide emergency: The childhood obesity

Childhood obesity is characterized by a chronic low-grade inflammation process detected through a panel of in- flammatory markers. Adipokines secreted from adipose tissue are key regulators of inflammation in obesity. Increased Tumor Necrosis Factor (TNF)- and Interleukin (IL)-6 levels as well as decreased adiponectin and IL-10 levels are associated with inflammation, tissue injury and complications of obesity. The recent discovery of High Mobility Group Box 1 (HMGB1) protein as a critical mediator of inflammation stimulated an increasing interest in inflammation research field. Obese children are characterized by high levels of this protein, closely related with other inflammatory cytokines, such as IL-6, TNF-, IL-18, resistin and adiponectin. Moreover, prolactin represents another risk marker for obese children and a predictive factor for pro- gression to metabolic syndrome. Leptin and ghrelin are two hormones playing key roles on energy balance. Leptin is responsible from long term regulation of metabolism and ghrelin functions as an appetite stimulatory signal. In contrast to ghrelin, obestatin acts as an anorexigenic hormone by suppressing food intake. Moreover, we also reviewed other gut-derived hormones involved in the regulation of food intake and energy homeostasis, such as amylin, peptide YY and glucagon-like peptide 1. All these peptides could represent important tools to detect eating disorders in children. The aim of this review is to better define the role of new peptides in childhood obesity. The diagnostic and prognostic role of these biomarkers was also assessed, highlighting potential strategies and proteomic medicine that could become possible in the near future.