Leila Mouelhi

Polymorphism in ICAM-1, PECAM-1, E-selectin, and L-selectin genes in Tunisian patients with inflammatory bowel disease.

Background Ulcerative colitis (UC) and Crohns disease (CD) are chronic intestinal disorders characterized by immune dysregulation and leukocytes recruitment into gastrointestinal tract. Cell adhesion molecules (CAM) mediate the extravasation of leukocytes and their accumulation in inflamed intestinal mucosa. Recently, CAM genes have been implicated in determining susceptibility to UC and CD. We investigate seven mutations in CAM: G241R and K469E in ICAM-1, V125L in PECAM-1, G98T, S128R, and L554F in E-selectin and F206L in L-selectin in 197 Tunisian patients (73 with UC and 124 with CD) and 194 controls. These polymorphisms were detected by polymerase chain reaction sequence-specific primers and restriction enzyme analysis. Results A significant increase in allele frequencies of 206L of L-selectin and the associated genotype F/L was observed in both patients with UC and CD compared with controls. Subgroup analysis showed that the L206 allele and F/L206 genotype frequencies were significantly increased in UC patients with left-sided type; whereas, the F/L206 genotype was significant in CD patients with ileocolonic location and stricturing behavior compared with controls. No significant differences in allele or genotype frequencies were observed for ICAM-1 K469E, E-selectin, and PECAM-1 polymorphisms between UC patients, CD patients, and controls. Conclusion We found an association of inflammatory bowel disease with allele L206 of L-selectin gene, whereas genotype L/F was associated with a subgroup of UC (left-sided type) and CD patients with more extensive location of disease and stricturing behavior. However, further studies are needed to confirm our findings.

Interleukin-18 gene polymorphisms in tunisian patients with inflammatory bowel disease.

Aim: Interleukin (IL)-18 can regulate the Th2-mediated immune response and it may be involved in the pathogenesis of Th1 and Th2 chronic inflammatory diseases. This study sought to detect a possible association between two single nucleotide polymorphisms (SNPs) (–137G/C and –607C/A) in the IL-18 gene promoter region and susceptibility to inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The (–137G/C and –607C/A) IL-18 polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the sequence-specific polymerase chain reaction method. Results: The distribution of allele and genotype frequencies illustrate that the –137G/G genotype frequency was significantly higher in UC than in controls (p value corrected (pc) = 0.038). On the other hand, we found a statistically significant association (pc = 0.033) between genotype AA of the IL-18 gene promoter (–607C/A) polymorphism in UC patients and the distal localization of the lesions. In CD, no significant differences were observed at positions –607 and –137. The analysis of IBD patients according to clinical behavior revealed no difference. Conclusion: The two SNPs at position –607 (C/A) and –137 (G/C) in the promoter region of the IL-18 gene was associated with the development of UC but not CD, providing a strong support for an IBD susceptibility gene in the region surrounding IL-18. It remains to be determined precisely how the IL-18 alleles influence the pathogenesis of IBD.

Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn’s disease

The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohns disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease.

Systemic lupus erythematosus and celiac disease.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 30 septembre 2011

Association between CTLA-4 Gene Promoter (49 A/G) in Exon 1 Polymorphisms and Inflammatory Bowel Disease in the Tunisian Population

Background/Aim: To investigate the possible association between the polymorphism of the CTLA-4 exon 1 +49 A/G and susceptibility to Crohns disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The +49 A/G dimorphism was analyzed in 119 patients with CD, 65 patients with UC, and 100 controls by the polymerase chain reaction–restriction fragment length polymorphism method. Results: Significantly higher frequencies of the CTLA-4 +49A allele and A/A homozygous individuals were observed in patients with CD when compared with controls (pc = 0.0023 and pc = 0.0003, respectively). Analysis of CTLA-4 A/G polymorphism with respect to sex in CD showed a significant difference in A/A genotypes between female patients and controls (pc = 0.0001 and pc = 0.038, respectively). There were no differences in the subgroups of patients with CD. Conclusions: Forty-nine A alleles and AA genotype are associated with CD susceptibility in Tunisians. Other genes involved in the T-cell regulation remain strong candidates for IBD susceptibility and require further investigation.

Genetic polymorphisms of inflammatory molecules in Tunisian inflammatory bowel diseases

As chemokines and adhesion molecules play a major role in the process by which leukocytes are recruited from the bloodstream into sites of inflammation [1], genetic variation in these production or activity molecules may influence susceptibility to inflammatory diseases [2-4].

Inflammatory pseudotumor of the liver associated with Crohn's disease

Inflammatory liver pseudotumor is a rare entity. Associations with several inflammatory conditions were reported but association with inflammatory bowel disease is unusual. We report the case of liver inflammatory pseudotumor occurring in the course of Crohns disease in a 23-year-old woman and treated conservatively.

Maladie de Crohn colique compliquée d’une fistule cologastrique et sigmoïdovésicale : diagnostic et prise en charge thérapeutique

La fistule gastrocolique est une complication rare de la maladie de Crohn. Son association à une fistule colovésicale est inédite et témoigne de l’agressivité de la maladie. La symptomatologie est souvent atypique et la triade classique associant douleurs abdominales, diarrhée et vomissements fécaloïdes n’est présente que dans 30 % des cas [1]. Le diagnostic positif de cette complication peut s’avérer difficile et repose essentiellement sur l’imagerie. Nous rapportons une nouvelle observation au cours de laquelle nous insistons sur l’approche diagnostique et les particularités thérapeutiques de cette affection.