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.

Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection.

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.

Anti-CCP antibodies, rheumatoid factors and anti-keratin antibodies: clinical value in established rheumatoid arthritis.

BACKGROUND: It is well documented that in early rheumatoid arthritis, anti-CCP antibodies have better diagnostic value than rheumatoid factors and anti-keratin antibodies. However, their role is less well defined in patients with established or long duration disease. AIM: To evaluate and to compare diagnostic performances of anti- CCP, anti-keratin, IgM and IgA rheumatoid factors in established rheumatoid arthritis. METHODS: In a cross-sectional study, 90 patients with established rheumatoid arthritis and 100 controls were tested for these autoantibodies. The association of these markers with disease activity and severity was investigated. The sensitivity and specificity were calculated for each of four tests, using the clinical diagnosis as the gold standard. RESULTS: The anti-CCP and IgM rheumatoid factor exhibited the best diagnostic value. None of the tested antibodies had any significant association with the disease activity score (DAS28). After adjustment by multiple linear regression, only anti-CCP positivity was found to be significantly associated with erosive disease. CONCLUSION: In long duration rheumatoid arthritis, anti-CCP and IgM rheumatoid factor have similar diagnostic value. However anti- CCP are useful in seronegative patients. They are also a reliable marker of severe erosive disease.

[IL1/IL1 Ra, CTLA-4 and Apo1/Fas genes polymorphisms and susceptibility to IgA nephropathy in Tunisian patients]. / Polymorphismes des gènes de l'IL1/IL1 Ra, CTLA-4 et Apo1/Fas et susceptibilité à la néphropathie à IgA chez des patients Tunisiens.

BACKGROUND: The IgA nephropathy (IgA-N) is considered the most common form of primary glomerulonephritis and its pathogenic mechanisms are very complex. The study of several genes which encode for immunoregulator molecules in inflammatory and immunological responses during the disease, allowed to describe some number of polymorphisms would be involved in the molecular expression, the road marking, the synthesis and\or the binding to the receptors. So an abnormality of the molecular function associated with its polymorphism would be suggested in the genetic predisposition to the disease. AIM: To determine interleukin 1 (IL1), interleukin1 receptor antagonist (IL1 Ra), CTLA-4 and Apo1/Fas genes polymorphisms frequencies in IgA-N in order to estimate the impact of these polymorphisms in the disease susceptibility. METHODS: The polymorphism of a single nucleotide (SNP) at (-889) IL1 a of 21 IgA-N patients and 100 healthy blood donors, as controls, was studied by PCRSSP. The SNPs of the IL1 ß (+3954), CTLA-4 (+49) and l'Apo1/Fas were analyzed by PCR RFLP and finally the polymorphism of the IL1 Ra gene was determined by a PCR VNTR (variable number tandem repeat). RESULTS: Investigation of IL1a/ß and Apo1/Fas polymorphisms showed no differences in genotypes and alleles frequencies between IgA-N patients and controls. However, genotype AA of CTLA-4 exon1 (+49) was significantly higher in patients (47.62%) than in controls (9.1%) p<0.001. Nevertheless, the clinical, histological and biological characteristics of IgA-N were similar in AA CTLA-4 genotype patients compared to AG or GG genotype patients. We fund also, a significant increased frequency of 1/1 IL1 Ra genotype in IgA-N patients (95.24%) compared to controls (54%) (p<0.001) (p<0.001). CONCLUSION: We conclude that the susceptibility to IgA-N seems to be associated with the presence of CTLA-4 AA and IL1 Ra 1/1 genotypes in Tunisian population. However, the lack of association between IL1 a/ß and Apo1/fas genes polymorphisms should be further investigated by large population based studies.

[Hepatitis C in kidney transplantation: comparative study between two Maghrebin centers: Casablanca and Tunis]. / L'hépatite virale C au cours de la transplantation rénale: étude comparative entre deux centres Maghrébins: Casablanca et Tunis.

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.

Human platelet antigens polymorphisms and susceptibility of thrombosis in hemodialysis patients.

To investigate the association between the polymorphisms of human platelet antigen (HPA)-1,2,3,4,5 and susceptibility to develop thrombosis accident in arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and 100 healthy blood donors were genotyped by PCR-SSP. The patients were classified into 2 groups: G1 included 54 HD patients presented at least one thrombotic episode on the level of the AVF, and G2 included 58 HD patients without any episode of thrombosis. The allelic frequencies of HPA-1, 2, 3, and 5 among patients and controls did not reveal significant differences. However, the HPA-4b allele was significantly more frequent in G1 than in controls or in G2 patients (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype distribution of HPA-4 polymorphism reveals that the HPA-4a4b genotype was more frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients with HPA-4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with HPA-4a4a genotype presented thrombotic episode (p<0.001). These results reveal a significant association between HPA-4a4b and thrombosis, and it is likely that HPA polymorphisms could be useful markers for potential risk of thrombosis in hemodialysis.

[Vascular trombosis of renal graft: 9 cases]. / Thromboses vasculaires du greffon apres transplantation renale: a propos de 9 cas.

BACKGROUND: Allograft renal thrombosis can occur in 1 to 6% of cases. Many predisposing factors has been identified especially alteration of coagulation. AIM: We analyzed in this study frequency and predisposing factors of renal graft thrombosis. METHODS: We report a retrospective study including 319 renal transplant recipients. RESULTS: Nine patients (2.8%) presented veinous graft thrombosis in 5 cases and arterial thombosis in 4 cases. There were 6 men and 3 women aged of 30.6 years meanly (10-56) which developed the thrombosis 6 days (1-48) after the transplantation. All patients were detransplanted after 16.2 days and 1 patient died. CONCLUSION: Thrombosis constitute an important cause of graft loss. A perfect surgical technic and prophylactic treatment in high risk patients are necessary to reduce this complication.

Clearance and persistence of hepatitis C virus in a Tunisian population: association with HLA class I and class II.

Human leukocyte antigens (HLAs) of class I and class II are reported to influence the outcome of hepatitis C virus (HCV) infection. The aim of this study was to assess the role of HLA class I and class II in influencing spontaneous viral clearance or persistence in HCV-infected patients. HLA class I (A and B) typing was performed by lymphocytotoxicity test and HLA class II (DRB1) was determined by low-resolution PCR-SSP (polymerase chain reaction amplification with sequence-specific primers) for 99 subjects (48 men and 51 women). Of these, 75 had chronic infection and 24 had viral clearance. No significant differences were observed between individuals with spontaneous viral clearance or chronic HCV infection for age, sex, source of infection, and risk factors. HLAB-w35 and HLA-DRB1*08 occurred more frequently in those with viral clearance (21.7 and 16.6%, respectively) compared with those with chronic infection (5.5 and 2.6%; p < 0.04 and p < 0.01, respectively). DRB1*15 occurred more often in those with chronic infection (29.3%) compared with those with viral clearance (16.66%), but the difference did not reach statistical significance. These results support the hypothesis that specific HLA class I and class II alleles might influence the clearance or persistence of HCV infection. Both Bw35 and DRB1*08 are associated with clearance of circulating HCV whereas DRB1*15 appears to predispose to progression of liver disease in Tunisian patients. Taken together, our results and those previously reported suggest that HLA associations with the outcome of hepatitis C viremia vary in relation to the ethnicity of the population studied. Further prospective studies of larger cohorts of HCV-infected subjects are needed to evaluate, in different populations, the role of specific HLA class I and class II alleles in the outcome of HCV infection.

Role of immune system, apoptosis and angiogenesis in pathogenesis of rheumatoid arthritis and joint destruction, a systematic review.

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.

Discrepancies of NKT cells expression in peripheral blood and in cerebrospinal fluid from Behçet's disease.

The precise role of natural killer T (NKT) cells in the pathogenesis of Behçet's disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42BD patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients (median: 0.06%; range: 0%-0.3%) when compared to healthy controls (median: 0.23%; range: 0.1%-0.7%; P<0.01). NKT cells were biased toward a Th(1)-like phenotype, with a significant decrease of IL-4/IFN-gamma ratio in BD (median: 0.049; range: 0.01-0.13) vs. healthy controls (median: 0.82; range: 0.4-1.33; P<0.01). NKT cells were increased in CSF-BD samples (median: 0.18%; range: 0.1%-0.4%), when compared to CSF-NIND patients (median: 0.05%; range: 0.01%-0.09%; P<0.01). Based on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide (alpha-GalCer), 80% of BD patients were non-responsive. At the opposite, the reactivity of NKT cells in CSF from BD patients was not impaired. BD-CSF NKT cells exhibited an increased expression of IFN-gamma-producing cells, demonstrating that CSF-NKT cells were functional, and biased toward a Th(1)-like phenotype. These data suggest that functional NKT cells are recruited into BD inflammatory sites contributing to BD pathogenesis.

Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's.

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.

The involvement of HLA -DRB1*, DQA1*, DQB1* and complement C4A loci in diagnosing systemic lupus erythematosus among Tunisians.

BACKGROUND: Genetic susceptibility to systemic lupus erythematosus (SLE) varies among populations. Few data exist on associations of HLA class II and class III alleles of the major histocompatibility complex (MHC) and susceptibility to SLE in Tunisians. PATIENTS AND METHODS: We compared HLA-DRB1*, DQA1, DQB1* and C4 allotypes in 62 Tunisian SLE patients and 100 matched controls. We also assessed the association of specific alleles with distinct autoantibody profiles in SLE patients. RESULTS: HLA-DRB1*0301, -DRB1*1501 and C4AQO alleles were increased in the SLE patients, while the frequencies of HLA-DRB1*04 and DQB1*03 were decreased. HLA-DQA1*0102 and DQA1*0501 were significantly increased in the SLE patients. HLA-DQB1*0201 and DQB1*0602 were more frequent in the SLE patients. C4A*QO and C4B*QO were increased in frequency in the SLE patients compared to the controls, but only C4A null was significantly increased. Eleven of 17 SLE patients with the C4 null allele were HLA-DRB1*0301 positive. Three of 16 SLE patients with HLA-DRB1*1501 were associated with HLA-DQB1*0501 rather than DQB1*0602, as has been reported in European SLE patients. CONCLUSIONS: The MHC class II alleles (DRB1, DQA1, DQB1) and C4 null associations noted in other ethnic groups are also found in Tunisians, suggesting shared susceptibility factors across ethnic lines in predisposition to SLE. In contrast to other ethnic groups, MHC class II alleles are not associated with the presence of specific autoantibodies in Tunisian SLE patients.

[A congenital deficiency of the C3 fraction of complement. A familial study]. / Deficit congenital de la fraction C3 du complement: Etude familiale.

The innate deficit of the third constituent of the complement is extremely rare, it appears clinically as a deficit of the humorale immunity. We report a case of C3 deficit in a 6 year old Tunisian child, who presents a psychomotor delay and recurrent infections. The investigation of the complement system profile by an immunochemical test of the children's serum shows an absence of C3 and C3d, associated to a loss of classic and alternate hemolytic pathway activities. The addition of functional C3 in the deficient serum restores the global hemolytic activity. The reconstruction of the hemolytic activity is dose dependent of C3 added quantity. The rate of C3 is lowered in the parent's with a 50% decrease of the global hemolytic activity. Immunochemical measurement of C3d confirms the absence of any C3 catabolism product in vivo. On the other hand (factor I) show a normal rate to all the family members.

[Immunological study in sickle cell disease patients: importance of the complement system]. / Etude immunologique du drepanocytaire homozygote: importance du systeme complementaire.

Ten Tunisian patients, with homozygote sickle cell disease and asplenia were studied to investigate and to determine possible immunological function defects. Obtained results directed us to an abnormality of the alternate complement pathway activation which is expressed by a decreased hémolytic activity, while the classic pathway is normal. Quantification of C3, C4, C5, C6, C7 and factor B by immunochemical assay were normal, whereas factor B functional activity was depressed to a mean level of about half of normal in eight patients, IgG was increased in one subject and IgA in two others. Numeration of Band T cells revealed slight decrease in proportion of CD3 and CD4 at one patient associated with an increase in B cells, but normal or increased absolute numbers of all cells population.

[The role of major histocompatibility complex genes in the pathogenesis of chronic inflammatory bowel diseases]. / Place des genes du complexe d'histocompatibilite dans la pathogenie des maladies inflammatoires chroniques de l'intestin.

Genetic factors, among which the HLA class II coding genes, are implicated in IBD pathogenesis. When considering the ethnic heterogeneity of the studied population and the IBD clinical heterogeneity, UC appears more dependent to HLA genes than CD. UC and HLA genes: HLA DR 4 gene would protect from UC. HLA DR2 gene, particularly the DRB 1 * 1502 allele, is predisposing for more severe forms necessitating a corticotherapy, while DRB 1 * 0301 allele is associated with less needs for surgery. CD and HLA genes: HLA DR 7 gene and the DRB 3 * 0301 allele predispose to CD, while HLA DR 2 and DR 3 genes may be protective factors. Thus, for MC patient, the DRB 1 * 0301/DQB*0201 haplotype might be associated with less occurrence of fistulas or severe forms requiring immunosuppressive therapy.

[Diabetes following kidney transplantation. Report of 35 cases]. / Diabète induit après transplantation rénale. A propos de 35 cas.

Post-transplant diabetes mellitus (PTDM) is a frequent complication of renal transplantation. It has a prevalence rate ranging from 3 to 46%. We undertook a retrospective study of 175 nondiabetic renal transplant recipients to determine the prevalence rate, clinical characteristics, and risk factors of PTDM in kidney transplant recipients in our region. Thirty five patients (20%) developed PTDM, 50% were diagnosed by 3 months post transplantation. Eight patients (22.8%) were insulin recurrent. PTDM was independent of kidney source, family history of diabetes, age, sex, incidence of acute rejection, body weight gain, steroid or cyclosporine dose, use of beta-blockers and cytomegalovirus infection. Acturial 5 years survival was 79.4% in the diabetic compared to 80.5% in the control group. Patient survival was similar in the two groups. We conclude that PTDM is frequent in our patients. No significant risk factors of PTDM were identified in this study.

Phylogenetic analysis of isolated HCV strains from tunisian hemodialysis patients.

The present study describes the strains of hepatitis C virus (HCV) isolated from Tunisian hemodialysis patients. Thirty-three HCV strains isolated from different dialysis centers in Tunis City were amplified by RT-PCR in a region of the NS5b gene, genotyped by sequencing, and compared to international sequences by phylogenetic analysis. The phylogenetic tree showed that 16 HCV isolates have been identified as subtype 4k (48.5%), 7 as unspecified HCV-4 subtype (21.2%), 5 as subtype 4a et 1b (each 15.2%). The analysis of this tree revealed that the HCV-1b strains were closely related to Anglo-Saxon and European isolates, while the HCV-4 isolates are genetically similar to Egyptian and African strains. Phylogenic analysis of 33 Tunisian isolates with international HCV strains on a region of the NS5b gene demonstrated that the subtype 4k submerged the Tunis city and a new subtype of HCV4 seems to be suspect in this area.

Chemokine and chemokine receptor gene polymorphism in Tunisian hemodialysis patients with HCV infection.

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.

CD86 +1057G>A polymorphism and susceptibility to acute kidney allograft rejection.

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. CONCLUSIONS: 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.

Lymphoid tyrosine phosphatase R620W variant and inflammatory bowel disease in Tunisia.

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.