La baisse de la densité osseuse au cours des maladies inflammatoires chroniques de l’intestin : prévalence et facteurs de risqué

Introduction: La baisse de la densité minérale osseuse représente la principale manifestation osseuse décrite au cours des maladies inflammatoires chroniques de l'intestin. En Tunisie, très peu d'études ont rapportés sa prévalence et ses facteurs de risque. Le but de ce travail était de déterminer la prévalence de la perte osseuse au cours des maladies inflammatoires chroniques de l'intestin, et rechercher ses facteurs de risque. Méthodes: Patients et méthodes: étude ouverte transversale, réalisée de 2007 jusqu'à 2012. Résultats: 146 cas étaient colligés, dont 105 avaient une maladie de Crohn (71,9%) et 41 avaient une rectocolite hémorragique (28,1%). Il s'agissait de 62 hommes et 84 femmes. L'âge moyen était de 33,18 ans. La perte osseuse était trouvée chez 85 patients (58,2%). Il s'agissait d'une ostéopénie dans 57 cas et d'ostéoporose dans 28 cas. Les facteurs de risque de perte osseuse étaient une activité physique limitée  (p=0,013), un indice de masse corporel '20 kg/m2 (p=0,015), une maladie active (p=0,035), l'étendue de l'atteinte intestinale (p=0,006) et une dose cumulée de corticothérapie dépassant 4,5g de Prednisone (p=0,003). Conclusion: La déminéralisation osseuse est une complication fréquente mais non constante. Ceci justifie un dépistage précoce chez les patients à risque, qui pourront ainsi bénéficier d'un traitement substitutif.Key words: Maladie de Crohn, recto-colite hémorragique, densité minérale osseuse, ostéopénie, ostéoporos

Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus

Pemphigus foliaceus (PF) is considered to be caused by the combined effects of susceptibility genes and environmental triggers. The polymorphisms of Toll-like receptors (TLRs) genes have been associated with the risk of various autoimmune diseases. The aim of this study was to evaluate the potential association of TLR2-3-4 and 7 gene polymorphisms with Tunisian PF. Fourteen polymorphisms were analyzed in 93 Tunisian PF patients compared to 193 matched healthy controls: rs5743703-rs5743709 and (GT)n repeat (TLR2); rs5743305, rs3775294, and rs3775291 (TLR3), rs4986790 and rs4986791 (TLR4); and rs3853839 (TLR7). Our results showed that the genetic factors varied depending on the epidemiological feature stratification. In fact, in the whole population, no association with the susceptibility to PF was found. The TLR2 GT repeat seems to be closely associated with PF risk in patients originated from the endemic localities (group 3); the GT18 allele and the heterozygous genotype GT18/GT19 seem to confer risk to endemic PF (P=0.02; OR=2.3 [1.1-4.9] and P=0.0002, OR=20 [2.5-171], respectively). In contrast, the GT23 repeat could be considered as protector allele (P=0.02, OR=0.2 [0.06-0.87]). Furthermore, medium GT alleles which induce high promoter activity were also significantly more frequent in patients versus short or long GT repeats (P=0.0018 with OR=3.26 [1.5-7]). On the other hand, the TLR3-rs574305 AA genotype and A allele were significantly more frequent in patients whose age of the onset was above 35 years (group 2) (P=0.038, OR=1.78 and P=0.009, OR=3.92, respectively). Besides, the TLR4>rs3775294 A allele was found to be protector only in patients with sporadic features (groups 2 and 4) (P=0.03, OR=0.57 [0.3-0.9] and P=0.006, OR=0.24 [0.08-0.74], respectively). No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-7 gene polymorphisms. The present data suggest that TLR2and TLR3 polymorphisms are significantly associated with increased susceptibility to PF in the Tunisian population

EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma

Tumor progression and recurrence of cervical cancer is associated with upregulation of matrix metalloproteinase 2 (MMP-2). We evaluated the location, origin, and activity of MMP-2 in cervical squamous cell carcinomas in comparison with MT1-MMP (MMP-14), TIMP-2 and EMMPRIN. Positive immuno-staining for MMP-2 in malignant cells was detected in 83% of the patients. Two patterns of tumor cell MMP-2 staining were observed: Either homogenous in all tumor cells or confined to the cells neighboring the stroma (tumor-border staining pattern, TBS). Fluorescence in situ zymography showed active MMP 2 mainly around tumor nodules displaying TBS. The MMP-2 staining of TBS tumors correlated significantly with the presence of TIMP 2 and MT1-MMP, proteins involved in docking MMP-2 to the cell surface, essential for MMP-2 activation. In situ mRNA hybridization in TBS tumors demonstrated more abundant presence of MMP-2 mRNA in neighboring myofibroblasts than in the adjacent tumor cells. Moreover, the TBS MMP-2 pattern correlated with the presence of EMMPRIN (P=0.023), suggesting that tumor cells induce MMP-2 production in nearby stromal cells. This pro-MMP-2 could subsequently be activated on tumor cells via the presence of MT1-MMP and TIMP-2. The biological relevance of this locally activated MMP-2 was underscored by the observation that only the TBS pattern of MMP-2 significantly correlated with decreased survival. In conclusion, the co-localization of EMMPRIN, MT1-MMP and TIMP-2 in human cervical carcinomas seems to be involved in a specific distribution pattern of tumor cell bound MMP-2, which is related with local proteolytic activity and therefore might be associated with worse prognosis of the patients