Association of Interleukin-6 and Interleukin-1 Family Gene Polymorphisms in Autoimmune Hepatitis.

INTRODUCTION AND AIM: Autoimmune hepatitis (AIH) is an immune-mediated destruction of liver cells, in recognition of interface hepatitis, seropositivity for autoantibodies, and interface hepatitis in histology sections. Hepatocyte destruction in AIH is the direct result of CD4+ T-cell destruction. Yet, Th17 mediated immune attach and a diversity of cytokine networks, including pro-inflammatory cytokines such as Interleukin 1 (IL-1) and Interleukin 6 (IL-6), set the stage for the destructive liver damage. MATERIAL AND METHOD: Peripheral blood samples from 57 patients, with AIH, recruited from referrals to the main pediatric hospital in Tehran. Single nucleotide polymorphisms for the following cytokines genes, were evaluated through, polymerase chain reaction with sequencespecific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-1α (C/T -511), IL-1ß (C/T +3962), IL-1 receptor (IL-1R; C/T Pst-I 1970), IL-1RA (C/T Mspa-I 11100), and IL-6 (C/G -174 and A/G nt565). RESULTS: Significant higher frequency of genotype AA was detected in patients in IL-6 at position nt565 (15.8% in AIH patients vs. 2.9% in controls, p = 0.003). The haplotype GA of IL-6 at -174 and nt565, was significantly overrepresented in the AIH group, compared to (20.9% of AIH vs. 1.4% in controls p < 0.0001). CONCLUSION: Results of our study, indicate significant deviation toward high yield IL-6 polymorphisms, in AIH patients. These data could bring new insights in pathophysiology of disease, which could contribute to developing novel treatments for AIH.

Evaluation of antibody response to polysaccharide vaccine and switched memory B cells in pediatric patients with inflammatory bowel disease.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

The effect of probiotics on fecal calprotectin in patients with cystic fibrosis.

Cystic fibrosis (CF) is a common autosomal recessive disorder with different clinical manifestations, mainly in the gastrointestinal and respiratory tracts. This study was performed to access the effect of probiotics in the status of intestinal inflammation in a group of children with CF by measuring the calprotectin level in the fecal samples. Forty-seven patients with CF were enrolled in this study. The fecal calprotectin levels were measured by enzyme linked immunosorbent assay. In a randomized systematic method, the children were divided into two groups - one group received probiotic powder and another received placebo for four weeks. After this period, fecal calprotectin was re-measured. Thirty-one of 47 enrolled patients (65.9%) had abnormal fecal calprotectin levels (>50 g/g). After the intervention, the fecal calprotectin levels decreased in 29 patients (21 patients in the drug group, and only 8 patients in the placebo group; p<0.001). This study showed that about two-thirds of patients with CF had intestinal inflammation based on fecal calprotectin levels. Probiotic administration was shown to decrease calprotectin concentrations and subsequently intestinal inflammation in CF patients.

The clinical and laboratory manifestations of Iranian patients with cystic fibrosis.

Cystic fibrosis (CF) is a hereditary disease, characterized by chronic pulmonary disease, pancreatic insufficiency and abnormal electrolytes in the sweat. In order to evaluate the clinical manifestations and laboratory findings of Iranian children with CF during a 10-year period, 243 CF patients, with a median age of 5 months, were investigated in this study. The most common manifestations were gastrointestinal disorders and respiratory manifestations. Cough was the most common symptom, followed by malnutrition, diarrhea, respiratory distress, and vomiting. The frequency of these findings after treatment was significantly decreased in comparison with the period before diagnosis. During the mean follow-up of 40.9 months, seven cases died due to severe infections. Cystic fibrosis as a common genetic disorder should be considered in any child with recurrent gastrointestinal and respiratory manifestations, since delayed diagnosis could lead to severe complications and even death in this group of patients.