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.

Vascular endothelial growth factor genetic polymorphisms and susceptibility to age-related macular degeneration in Tunisian population.

Purpose: Three VEGF SNPs (-2578) C/A, (+405) G/C and (+936) C/T were investigated in Tunisian exudative AMD patients in order to determine their association with the disease susceptibility and their influence to intravitreal bevacizumab therapy response.

Methods: 145 AMD patients and 207 age-matched controls were included. 68 patients were treated with intravitreal bevacizumab.

Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney transplantation.

Background: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance.

Objectives: We investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival.

Cytokine gene polymorphisms in kidney transplantation.

Background: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft.

Objectives: We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection.

MCP-1, CCR2 and CCR5 polymorphisms in Tunisian patients with atopic asthma.

Chemokines and their receptors play an important role in the late inflammatory stage of asthma. In this study, we aimed to investigate polymorphisms of MCP-1 (CCL2), CCR2 and CCR5 which can affect qualitatively and/or quantitatively their production and thus influence both susceptibility and severity of asthma and its clinical and biological features.MCP-1 (A/G -2518), CCR2 (+/64I), CCR5 (G/A -59029) and CCR5 (∆32) polymorphisms were evaluated by PCR in 107 Tunisian patients with asthma and 169 healthy controls.

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.

Investigation of DNA sequence in the Basal core promoter, precore, and core regions of hepatitis B virus from Tunisia shows a shift in genotype prevalence.

Background: In this study, we evaluated the prevalence of the most common mutations occurring in Enhancer II (EnhII), Basal Core Promoter (BCP), Precore (PC), and Core (C) regions of hepatitis B virus (HBV) genome.

Objectives: We also investigated the correlation between HBV variants, their genotypes, and patients' HBe antigen (HBeAg: soluble shape of the capsid antigen) status.

Patients And Methods: We retrieved viral DNA from 40 serum samples of Tunisian patients positive for hepatitis B surface antigen (HBsAg) and HBV DNA, amplified the above mentioned regions using specific primers, and sequenced the corresponding PCR (polymerase chain reaction) products.

Y402H polymorphism in complement factor H and age-related macular degeneration in the Tunisian population.

To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active.

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.

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.

Genetic polymorphisms of inflammatory molecules in Tunisian kidney transplantation.

As chemokines and adhesion molecules play major roles in the process by which leukocytes are recruited from the bloodstream into sites of inflammation, genetic variations in the production or activity of molecules may influence susceptibility to acute rejection episodes. This study sought to determine the impact of recipient monocyte chemoattractant protein-1 (MCP-1), chemokine receptor (CCR2, CCR5), and adhesion molecule (ICAM-1, PECAM-1 and L/E selectin) polymorphisms on acute rejection after renal transplantation. We selected 169 healthy blood donors and 173 renal transplant recipients for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation.

Allograft renal rejection and chemokine polymorphism.

Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association, we analyzed polymorphisms of CCR5-∆32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518) in 173 renal transplant recipients and 169 healthy blood donors.

Association of chemokine and chemokine receptor polymorphisms with activity degree of IBD in Tunisian patients.

Crohn's disease (CD) and ulcerative colitis (UC) have complex genetic background that is characterised by more than one susceptibility locus. To detect a possible association between the functional polymorphisms of the chemokine receptors CCR5, CCR2 and MCP-1 genes and susceptibility to CD and UC in Tunisian population, polymorphisms of CCR5-delta32, CCR5-59029-A/G, CCR2-V641 and MCP-1-2518-G/A were analysed in 194 Inflammatory bowel disease (IBD) patients and 169 healthy blood donors using PCR-RFLP and PCR-SSP methods. The patients were classified in 126 patients with CD and 68 patients with UC.

(AT) repeat in the 3' untranslated region of the CTLA-4 gene and susceptibility to acute allograft rejection in Tunisian renal transplantation.

Allograft rejection is an immune response relying on the proliferation and the differentiation of T cells. CTLA-4 is a co-stimulatory molecule, expressed on activated T lymphocytes, which has been shown to play a crucial role in the down-regulation of T-cell activation. Herein, we have examined the impart of a genetic marker in the CTLA-4 gene on renal transplant outcomes.

[Hepatitis C in kidney transplantation: comparative study between two Maghrebin centers: Casablanca and 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):.

[IL1/IL1 Ra, CTLA-4 and Apo1/Fas genes polymorphisms and susceptibility to IgA nephropathy in Tunisian patients].

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.

Role of genetic polymorphisms in factor H and MBL genes in Tunisian patients with immunoglobulin A nephropathy.

The molecular mechanisms of IgA nephropathy (IgAN) remain poorly understood. Several different polymorphic genes have been investigated in order to demonstrate their possible association with this disease. It is evident that mainly alternative and lectin pathways complement activation and play an important role in renal injury of IgAN.

Association of specific amino acid sequence (QRRAA) of HLA-DRB1*0405 with rheumatoid arthritis in a Tunisian population.

This study aimed to investigate HLA-DRB1 alleles in rheumatoid arthritis (RA) patients from Tunisia and to examine the effect of these alleles on disease severity. HLA-DRBI alleles and sub-typing of DRBI*04 and *01 were determined in 90 patients and 100 healthy controls, by PCR-SSP. HLA-DRB1*04 was significantly higher in patients (51.

Genetic polymorphisms of immunoregulatory proteins in acute renal allograft rejection.

CTLA-4 and CD28 are T lymphocyte receptors involved in the regulation of T-cell activation. Allograft rejection is an alloimune response which is strongly dependent on T-cell proliferation. Thus, we examined the relationship between CTLA-4 and CD28 gene polymorphisms and renal transplant outcomes.

The PTPN22 C1858T (R620W) functional polymorphism in kidney transplantation.

To investigate the association between kidney transplant rejection and PTPN22 (protein tyrosine phosphatase non-receptor 22) polymorphism, genomic DNA of 175 renal transplant recipients and 100 healthy blood donors were genotyped by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2 included 142 with one or more HLA mismatches. Forty-nine patients developed an acute rejection episode (ARE): 8 in G1 and 41 in G2.

Kidney transplantation: Charles Nicolle Hospital experience.

The aim of our retrospective study was to analyze the short- and long-term follow-up of 298 renal transplantations performed between June 1986 and May 2005. All were first transplantations except 4 cases, with 54 from cadaveric and 244 from living donors. The recipients included 196 males and 102 females of overall mean age of 31.

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

Background: Ulcerative colitis (UC) and Crohn's 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.

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.

Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis.

To investigate a possible association between functional polymorphisms of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22-R620W) and receptors for the Fc fragment of IgG (FcgRIIa-H131R, FcgRIIIa-F158V FcgRIIIb-NA1/NA2), and rheumatoid arthritis (RA), 133 Tunisian patients with RA and 100 controls were genotyped. We found strong evidence of an association of PTPN22 620W allele and RA. However, analysis does not detect an association between auto-antibodies seropositivity, presence of nodules or erosions and this allele.

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.