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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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction. CD86 is a costimulatory molecule that participates in the regulation of T-cell lymphocytes activation. Thus, we examined a genetic marker on the CD86 gene in kidney transplant outcome. Materials and Methods. In our retrospective study, 168 kidney allograft recipients were genotyped by direct sequencing. Patients were classified into 2 groups of 29 human leukocyte antigen (HLA)- identical haplotype allograft recipients and 139 recipients showing one or more mismatches in the HLA haplotype. Forty-five patients (26.8%) developed at least 1 acute rejection (AR) episode, 7 in the first and 38 in the second group. Results. Acute rejection was associated with the presence anti-HLA antibodies before transplantation (P = .03). The AA genotype and A allele at position +1057 in the CD86 gene were more frequent in patients without AR (9.75% and 28.5%, respectively) compared with those showing an AR (2.22% and 23.3%, respectively). This difference was statistically significant in the anti-HLA-positive recipients, as AA frequency was 31.3% in non-AR patients and zero in AR ones (P = .04) and A allele frequency was 46.9% and 20.8%, respectively (P = .04). Patients bearing AA genotype reached a higher graft survival time (9.84 years) than those carrying GA (8.21 years, P = .32) or GG (7.61 years, P = .72) genotypes. Conclusion. These results suggest that AA genotype and A allele of CD86 +1057G>A polymorphism may confer a protection against acute kidney allograft rejection in Tunisian patients. [ABSTRACT FROM AUTHOR]

Introduction: Clopidogrel (clopi) is a prodrug widely prescribed in the management of coronary artery disease and requires the intervention of hepatic cytochrome P450 2C19 (CYP2C19) for its activation. However, there is interindividual variability in response to clopi despite the use of recommended doses. Thus, the studies have highlighted the effect of the CYP2C19 gene polymorphism or Cyp2C19 gene on the response to clopi and particularly Cyp2C19 * 2 which may be associated with an increased risk of major cardiovascular events or MACE., Objective: To evaluate the effect of Cyp2C19 * 2 polymorphism on MACE occurrence and hemorrhagic complications in patients treated with clopi., Methods: We carried out a descriptive longitudinal study including 71 patients placed under clopi for a minimum duration of one month. Genotyping of the Cyp2C19 allele was performed by conventional polymerase chain reaction (PCR). After a follow-up period of 495 ± 183 days, we performed a statistical analysis to evaluate the association between the Cyp2C19 * 2 polymorphism and the occurrence of MACE or hemorrhagic complications., Results: Among our patients, 51% had an angioplasty, 42% medical treatment and 7% a coronary artery bypass surgery. In our study population, 52% were heterozygous (HTZ), 28% homozygous (HMZ) healthy * 1 / * 1 and 20% HMZ had the loss of function allele * 2 / * 2. The allelic frequency of Cyp2C19 * 2 was 46%. Follow-up mean duration was of 495 ± 183 days. During this period, the prevalence of MACE was 11% and that of hemorrhagic complications was 13%. In our study, we did not observe a significant association between the occurrence of MACE or hemorrhagic complications with the genotype carrying the Cyp2C19 * 2 allele., Conclusion: Among patients treated with clopi, wearing a Cyp2C19 * 2 function loss allele didn't seem to be associated with a significantly higher risk of MACE, nor a significantly lower risk of hemorragic complications. This suggests the necessity of larger studies.

Aim: To analyze the polymorphisms of CTLA-4 gene involved in the response against hepatitis C virus (HCV) infection., Methods: We recruited 500 hemodialysed patients from several hemodialysis centers, all HCV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the Charles Nicolle hospital Tunisia, classified into two groups G1 (PCR+) and G2 (PCR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PCR-RFLP was performed for the analysis of SNPs (+49) A/G and (+6230) G/A CTLA-4 for these 500 patients and 358 healthy controls., Results: Analysis of clinical and virological characteristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG (+49)/(CT60) CTLA-4 in the entire patients group compared to controls (P = 0.0036 and OR = 1.42; 95%CI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HCV infection., Conclusion: Our study suggests a possible role of CTLA-4 polymorphisms in the outcome of HCV infection in the Tunisian hemodialysed population.

Epithelial-mesenchymal transition (EMT) is a process by which differentiated epithelial cells undergo a phenotypic conversion and acquire a mesenchymal phenotype, including elongated morphology, enhanced migratory and invasion capacity, and greatly increased production of extracellular matrix (ECM) components. This phenomenon plays a pivotal role in embryonic development, wound healing and tissue regeneration. It has also been involved in organ fibrosis. Some studies suggest that following injury, renal tubular epithelial cells undergo reprograming in mesenchymal cells, and thus constitute an important source of de novo myofibroblasts invading the renal interstitium and contributing to fibrosis. However, an increasing number of studies raise doubts about the existence of this process in vivo. The role of EMT in the development of renal fibrosis remains a matter of intense debate and may depend on the model studied. In this review, we describe the role of EMT in the development of fibrosis of renal graft, and then we propose approaches for detecting and treating renal fibrogenesis by targeting TEM., (© 2015 médecine/sciences – Inserm.)

Introduction: Our aim was to investigate the possibility of a significant relationship between chemokines and chemokine receptor genes polymorphisms and the spontaneous clearance or the persistence of HCV infection., Methods: A total of 96 hemodialysis (HD) patients infected with HCV were classified into two groups: G1 included 73 patients with persistently positive HCV-RNA and G2 included 23 HD patients who have spontaneously eliminated the virus. The control group consisted of 170 healthy blood donors. All subjects were genotyped for CCR5 ?32, CCR5 (-59029) A/G, CCR2 (64Ile) and MCP-1(-2518) A/G gene polymorphisms., Results: Our results showed a statistically significant increased frequencies of the CCR2 (64Ile) and the (-59029) CCR5 A alleles in patients infected with HCV (22.1% and 35.9%) compared to G1 (24.3% and 40.6%) and compared to controls (14.4% and 20%). We also observed a lower frequency of the MCP-1 G allele and a greater frequency of the CCR5?32 variant in G2 (15.2% and 6.5%) compared to G1 (22.6% and 1.4%) that was not statistically significant. However, adjustment for known covariates (age, gender and HCV genotypes) didn't confirm the results of univariate analysis., Conclusion: In conclusion, our study suggests a possible role for some of the studied chemokines polymorphisms in the spontaneous clearance or persistence of HCV infection in Tunisian population. These results should be further investigated by a prospective cohort studies and large population-based studies.

Background: Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood. This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis., Methods: Polymorphisms of the genes IL-1 (-889 IL-1alpha, -511 and +3954 IL-1beta, IL-1Ra), IL-18 (-137 and -607), IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP, PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis. The patients were classified into two groups: G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA)., Results: The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008; OR=0.26; 95% CI, 0.10-0.73). We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026; OR=3.49; 95% CI, 1.13-10.69). Adjustment for known covariate factors (age, gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and -607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017, respectively)., Conclusion: The two genotypes GC-CA of the (-137 and -607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.

Background: Hepatitis viral C (HVC) is relatively frequent among kidney transplants. It is responsible for a morbid-mortality that compromises the results of transplantation in the medium and long term., Aim: To evaluate and to compare the prevalence of HVC, 172 kidney transplant adult patients were investigated in two Maghrebian centers at Casablanca (G1): 57 Moroccan patients and Tunisia (G2):.115 Tunisian patients. The impact of the HVC infection for a morbid-mortality was concerned only the Tunisian recipient patients: 20 kidney recipients having antibodies anti-VHC and positive HVC-RNA (Cases) which were matched in age, sex and date of the kidney graft, to 20 kidney transplant patients anti-HVC and VHCRNA negative (Controls)., Methods: The anti-VHC antibodies were detected by ELISA: Innogenetics and their positivity were confirmed by RIBAII. The ARN-VHC was analyzed by RT-PCR INNO-LiPA HCV II amplification of Innogenetics., Results: The prevalence of hepatitis C is similar for the two groups: 19.3% among Moroccan kidney transplants and 20.9% among Tunisians. The infection by the HVC was often active and the detection of viral RNA was found in 91.7% of the G2 patients against 50% among G1 patients. The genotype 1b is the most prevalent; it is found in 59% of the patients. The frequency of HVC among our kidney transplant patients is particularly determined by the duration and the mode of dialysis. In fact, 22.1% of the patients treated by hemodialysis are VHC (+) against 5,6% patients treated by peritoneal dialysis. Also, the average duration of the dialysis is 58,8 months for HVC (+) patients against 33.5 months for HVC (-) (p<0.0001) patients. The frequency of the chronic rejection of the graft is higher in the G2, but it is similar in Tunisian patients with or without antibodies anti-HVC. In the G1, this frequency is statistically higher among positive HVC transplant patients compared to the negative HVC grafted patients (p<0.05). The case-control study emphasizes the frequency of the proteinuria, the renal insufficiency, the mellitensis diabetes and the polyglobulinemia among patients HCV (+); however the differences between the two groups remain statistically non significant. The total rate of the hospitalizations is 26 per 100 patients per year in the HCV (+) group against 17 for the HCV (-). The average duration of hospitalizations is 72 days among HCV (+) patients against 30.2 days for the controls (p<0.05). The averages of survival of the patients and of the controls were similar 11.6±5.6 years for transplant patient HCV (+) against 11.2±5.5 years for the controls. The actuarial curves of the patients were not different for the patients having antibodies anti-HCV positive or negative., Conclusion: The blood and nosocomial modes of contamination of HVC infection explain their higher frequency in this population at risk. The mortality and the morbidity of the renal transplant patients infected by the HCV seem to be higher compared to the uninfected patients. A further study by large population should be carried out to confirm these results.

Aim: To assess the possible association between PTPN22 (R620W) gene polymorphism and inflammatory bowel disease (IBD)., Methods: One hundred and sixty-four patients with IBD [105 Crohn's disease (CD) and 59 ulcerative colitis (UC)] and 100 healthy controls were recruited. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by restriction fragment length polymorphism-polymerase chain reaction with RsaI digestion., Results: The genotypic and allelic frequencies of (R620W) PTPN22 gene polymorphism reveal a significant association of the PTPN22 620-W allele with IBD, compared to the healthy control group (OR: 17.81, 95% CI: 4.18-21.86, P = 0.00001). Nevertheless, no difference in this polymorphism was found between CD and UC patients. No significant association was found between the frequencies of genotypes of the PTPN22 gene with either the clinical features such as sex, age, age at disease onset, and extent of colitis, or the production of serological markers (anti-Saccharomyces cerevisiae antibody in CD and perinuclear anti-neutrophil cytoplasmic antibody in UC)., Conclusion: These observations confirm the association of IBD susceptibility with the PTPN22 1858T (620-W) allele in Tunisian patients.

Aim: To detect a possible association between the polymorphism of the (-670 A/G) Fas/Apo1 gene promoter and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population., Methods: The (-670 A/G) Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method., Results: Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of (-670 A/G) Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls (P corrected = 0.004 in CD patients and P corrected = 0.02 in UC patients, respectively). Analysis also showed a statistically significant association between genotype AA of the (-670 A/G) polymorphism and the ileum localization of the lesions (P corrected = 0.048) and between genotype GG and the colon localization (P corrected = 0.009). The analysis of inflammatory bowel disease patients according to clinical behavior revealed no difference., Conclusion: Fas-670 polymorphism was associated with the development of CD and UC 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 Crohn's 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.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder of unknown cause that is notorious for the chronic polyarticular synovial inflammation and progressive destruction of affected joints. Understanding the pathogenesis of RA provides the basis for optimal management of that disease in patients. The pathogenesis of RA was largely explored in many studies in human as much as in mice models with collagen II induced arthritis, nevertheless the pathogenesis puzzle is still incomplete., Aim: The aim of this systematic review was to collect the results of many observations and to put them down into an original story of RA set up., Methods: An exhaustive electronic and library search of the relevant literature was carried out through "science direct" and "interscience wiley" web sites. The key words used for the search were "rheumatoid arthritis", "pathogenesis", "apoptosis", "angiogenesis", "immune response" and "joint destruction"., Results: The suspected responsible antigen isn't yet determined although the great specificity of anti-CCP antibodies suggests that this antigen carries probably many citrullinated residues. The immuno-pathogenesis of RA involves both the innate and the adaptive immune system. In the other hand, apoptosis defect contribute to hyperplasia of rheumatoid synovium and in extended half life of fibroblast like synoviocytes (FLS), neutrophils and many other cells implied in rheumatoid synovitis. Hyperplasia of synovium leads to ischemia and that results in neo-angiogenesis with increase of proangiogenic factors such as VEGF. The last part of the pathogenesis of RA is the joint destruction resulting from increased MMP production and activation of osteoclasts which leads to the breakup of cartilage and to bone damage.