ABSTRACT
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. 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. 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. 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
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. To determine interleukin 1 [IL1], interleukin1 receptor antagonist [IL1 Ra], CTLA-4 and Apol/Fas genespolymorphisms frequencies in IgA-N in order to estimate the impact of these polymorphisms in the disease susceptibility. The polymorphism of a single nucleotide [SNP] at [-889] IL1 alpha of 21 IgA-N patients and 100 healthy blood donors, as controls, was studied by PCRSSP. The SNPs of the IL1 beta [+3954], CTLA-4 [+49] and l'Apol/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]. Investigation of IL1 alpha/beta and Apol/ Fas polymorphisms showed no differences in genotypes and allelesfrequencies between IgA-N patients and controls. However, genotype AA of CTLA-4 exon 1 [+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]. 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 alpha/ beta and Apol/fas genes polymorphisms should be further investigated by large population based studies
ABSTRACT
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 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 immune-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