Celiachia e difetti dello smalto in età evolutiva: correlazione tra periodo di esposizione al glutine, forme cliniche di celiachia e aplotipo HLA

The association between celiac disease (CD) and dental enamel defects (DED) is well known. AIM: This study was designed to investigate the prevalence of DED in CD children and to specifically find a possible correlation between DED and gluten exposure period, CD clinical forms, HLA class II haplotype. MATERIALS AND METHODS: This study was designed as a matched case-control study: 374 children were enrolled (187 celiac and 187 non celiac). Data about age at CD diagnosis, CD clinical form and HLA haplotype were recorded. RESULTS: DED were detected in 87 celiac subject while no dental lesions were found in the remaining 100 patients; in 187 healthy controls enamel lesion were significantly less frequent (5.3 % versus 46.5% ; p<0.005).We found a correlation between DED and gluten exposure period, since among CD patients the mean age at CD diagnosis was significantly (p= 0.0004) higher in the group with DED (3.41± 1.27) than without DED (1.26± 0.7). DED resulted more frequent in atypical and silent forms than in the typical one. The presence of HLA DR 52-53 and DQ7 antigens significantly increased the risk of DED (p=0.0017). CONCLUSIONS: Our results confirmed a possible correlation between CD clinical form, age at CD diagnosis, HLA antigens and DED. The origin of DED in CD children is due to multifactorial events and further studies are needed to investigate other determinants.

Alterazioni dell'immunità umorale nei pazienti con sarcoma di Kaposi classico: caratterizzazione dei linfociti B circolanti e delle loro sottopopolazioni

Objectives: Human Herpesvirus 8 (HHV-8) is the etiological agent of Kaposi’s Sarcoma (KS) and it is also associated with two B cell lymphoproliferative diseases: primary effusion lymphoma (PEL), and the plasmablastic form of multicentric Castelman’s disease (MCD). HHV-8 establishes persistent infection in the host with tropism for multiple cell types. In KS patients, the virus is found in tumor-spindle cells, peripheral blood monocytes, endothelial progenitor circulating cells, T and B lymphocytes. Peripheral B cells represent one of the major virus reservoir, but the consequences of HHV-8 infection of these cells have been poorly characterized. Therefore, in this study the frequency, the immunophenotypic profile and the functional activity of different peripheral B cell subsets in patients with classic KS (cKS) was analysed in order to identify potential alterations of these cells. The classic variant of KS is ideal to perform such studies, as it lacks confounding factors such as HIV or EBV infection and immunosuppression. Methods: Whole-blood samples from patients with the classical form of KS (cKS) (n=62) and healthy age and sex-matched seronegative controls (HSN) (n=43) were analyzed by multiparametric flow-cytometry to determine the frequency of B cells and their subpopulations, as well as their surface expression of immunoglobulins and activation markers. Results: The frequency of circulating B cells was significantly higher in cKS patients than in controls. In particular, the analysis of the B cell subsets revealed a higher frequency of naïve B cells (CD19+CD27-), among which transitional CD19+CD38highCD5+ and pre-naïve (CD27-CD38intCD5+ ) B cells demonstrated an expansion. Memory B cells (CD19+CD27+) did not differ between the two study groups, except from a higher frequency of CD19+CD27+IgM+IgD+ B cells, the typical phenotype of marginal zone (MZ) B cells, in cKS patients. The characterization of membrane surface activation markers showed lower levels of the activation marker HLA-DR only on CD27- B cells, while CD80 and CD86 were less represented in all the the B cells from cKS patients. Moreover, B cells from cKS patients were smaller and with less granules than the ones from controls. Conclusion: Taken together, these results clearly indicate that circulating B cells are altered in patients with cKS, showing an expansion of the immature phenotypes. These B cell alterations may be due to an indirect viral effect rather than to a direct one: the cytokines expressed in the microenvironment typical of cKS may cause a faster release of immature cells from the bone marrow and a lower grade of peripheral differentiation, as already suggested for other chronic viral infections such as HIV and HCV. Further studies will be necessary to understand how these alterations contribute to the pathogenesis of KS and, eventually, to the different clinical evolution of the disease.

Espressione del vascular endothelium growth factor (VEGF) nella micosi fungoide

La micosi fungoide (MF) è un linfoma a cellule T primitivo della cute usualmente indolente negli stadi iniziali, ma con prognosi decisamente peggiore nelle fasi avanzate, ove attualmente non sono presenti strategie terapeutiche tali da indurre remissioni durature. Recenti osservazioni indicano che alti livelli di espressione del vascular endothelial growth factor (VEGF) nelle cellule della MF sembrano correlare con una prognosi peggiore. Nel presente studio, sono state vagliate le eventuali differenze di espressione di VEGF nella MF e nei linfociti T normali. In primo luogo sono stati raffrontati 63 casi di MF con 20 campioni corrispondenti alle diverse sottopopolazioni di linfociti T normali, per stabilire quale fra questi esprimesse maggiori livelli di VEGF. Tale esperimento ha dimostrato che il gene è notevolmente più espresso nella MF. Si è provveduto a stabilire se tale dato sia da correlarsi ad un fenomeno patologico o fisiologico. Quindi sono state eseguite indagini di gene expression profiling (GEP) allo scopo di vagliare i livelli di VEGF nella popolazione linfocitaria T normale (CD4+, CD8+, HLA-DR+ e HLA-DR-): da ciò è risultato che i linfociti T attivati esprimono maggiormente VEGF e che il loro GEP è globalmente paragonabile a quello della MF. Pertanto, i linfociti T attivati sono stati considerati la controparte normale delle cellule della MF. Successivamente si è confrontata l’espressione quantitativa di VEGF nei linfociti T attivati e nelle cellule della MF, evidenziando come questa sia maggiore nella popolazione neoplastica indipendentemente dallo stadio della malattia. Le indagini immunoistochimiche condotte su 18 casi di MF, hanno confermato quanto evidenziato attraverso il GEP. Concludendo, la ricerca ha dimostrato per la prima volta l’espressione di VEGF negli elementi della MF. Ciò porta a supporre che la de-regolazione genica della via di VEGF sia correlata nella patogenesi della MF e che tale molecola possa considerarsi un potenziale bersaglio terapeutico.