Giovanna Di Dio

Hepatitis B vaccine in celiac disease: Yesterday, today and tomorrow

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

Liver Disease in Cystic Fibrosis: an Update

Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.

Heart involvement in children and adults with cystic fibrosis: correlation with pulmonary indexes and inflammation markers.

BACKGROUND Cardiovascular involvement in Cystic Fibrosis (CF) is a not rare condition, although the prevalence of subclinical pulmonary hypertension (PH) and cardiac dysfunction is not known in the early stages of CF progression. The aim of our study was to assess cardiac involvement in children and adults affected by cystic fibrosis compared with healthy subjects of same age using echocardiography. METHODS Fifty-five patients, 25 adults and 30 children completed the study. We assessed FEV1 (Forced Expiratory Volume in one second), and carried out colour Doppler-echocardiography evaluating ejection fraction (EF) measurement of left ventricle, tricuspid annular plane systolic excursion (TAPSE) of right ventricle and pulmonary artery pressure (PAP). We compared the auxological, respiratory and cardiologic data with those of 16 adults and 34 children of the same age. RESULTS We discovered significantly different values of PAP between patients and controls in both children (p = 0.0001, r=- 0.62) and adults (p=0.0001, r=- 0.63), whereas the EF and TAPSE showed significantly different values in only adults (p=0.0023 and p=0.0194 respectively). We found in both children and adults with CF an inverse correlation between PAP and FEV1 (p=0.000, p=0.001), Erythrocyte Sedimentation Rate (ESR) and FEV 1 (p=0.015, r=- 0.43; p=0.009, r=- 0.51), and highly sensitive C-reactive protein (hs-CRP) and FEV 1 (p=0.007, r=- 0.48; p=0.001, r=- 0.60). In adults we also detected direct correlation between PAP and hs-CRP (p=0.008, r=0.51) and PAP and ESR (p=0.009, r=0.51). CONCLUSIONS In paediatric-aged CF patients there are already early signs of potential heart impairment, represented by an increase of pulmonary blood pressure, and in adult age the systolic function of right ventricle may be impaired. We hypothesise that such cardiac impairments may gradually arise due to preceding chronic inflammation related to prior degeneration of lung function and thus it is very important to keep patients clinically stable and address chronic inflammation as early as possible in the progression of CF.

Immune system network in allergic diseases during sublingual immunotherapy: The role of oral mucosal tissue

Specific sublingual immunotherapy (SLIT) represents an approach currently available to redirect inappropriate immune response in atopic patients. Since oral mucosal tissue displays high affinity for allergens, it is conceivable that the sublingual administration route might induce immunological tolerance towards allergens involving cells and mediators specific of oral and intestinal mucosa. The presence in oral mucosa of dendritic cells (DCs) which express the high-affinity receptor for immunoglobulin (Ig)E (FceRI) seems to suggest that the generation of T regulatory cells in periphery is orchestrated by a particular subset of DCs. It seems that repeated stimulation of naive CD4 T cells with allogenic immature DCs induce Tr1 cell maturation. Nevertheless, other cells are involved in this process, such as Toll Like Receptors (TLR), Major Histocompatibility Complex I and II (MHC I and II) and costimulatory molecules, such as CD40, CD 80/B7.1 and CD 86/B7.2. An increase of serum IgG4 and IgA, a reduced number of inflammatory cells infiltrating target organs, as well as a reduction of eosinophilic cationic protein and a T cell suppression in the peripheral blood also occur with SLIT. All these molecules orchestrate the immune network within the regional immune system, recreating a favourable environment for the induction of tolerance operated by SLIT.

Cytomegalovirus colitis and cow's milk allergy in an immunocompetent infant: Is a causal or casual relationship?

Bloody diarrhoea in infants is an alarming symptom and requires further investigations. Cytomegalovirus (CMV) colitis is a cause of blood per rectum in combination with diarrhoea in infancy [1]. CMV colitis is one of the systemic manifestations of the CMV infection in immunocompromised hosts, while in immunocompetent hosts the CMV infection remains usually asymptomatic or, at most, manifests as nonspecific viral syndrome or mononucleosis syndrome. Therefore, it has a benign and self-limiting course and rarely causes systemic manifestations [2]. Infants are in the middle between immunocompetent and immunocompromised hosts because the immune system develops over the course of months of life and is influenced by breastfeeding mothers. Only few cases of CMV colitis in immunocompetent hosts have been previously reported in the literature [3-7]. We describe a case of colitis due to primary postnatal CMV infection in an immunocompetent infant who manifested bloody diarrhea, lack of appetite and weight loss associated with fever. Interestingly, the CMV colitis was associated to the CMPA (cow’s milk protein allergy). The possible relation between CMV colitis and CMPA is still unclear.

Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients

BackgroundThe p.Leu1077Pro CFTR mutation was firstly described in 1992 as a mild allele that confers a pancreatic sufficiency phenotype but the information collected in database CFTR2 lead to consider p.Leu1077Pro as a severe CF mutation. Although it is typical of Southern Italy, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area. The aim of our study was to describe prevalence and clinical features in patients bearing this mutation followed in our Cystic Fibrosis Centre to demonstrate that this mutation should be included in the mutation panel firstly tested in patients originated from Southern Italy.FindingsWe reviewed data from a cohort of 111 cystic fibrosis patients. 4 patients who were heterozygous for the p.Leu1077Pro mutation were included in the study.In our Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had positive sweat test values, pancreatic insufficiency and pulmonary exacerbations. One out of four patients even showed both FEV1 and FVC values significantly below the normal range, the presence of bronchiectasis and chronic Pseudomonas aeruginosa colonization.ConclusionsWe found that the p.Leu1077Pro CFTR mutation is associated with a classic CF phenotype confirming what is reported in CFTR2 database. The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy.