To investigate the expression of CD28 and CTLA-4, two costimulatory molecules involved in T-cell activation at the maternal-fetal interface in women with unexplained pregnancy loss.
A total of 57 women, 39 with unexplained spontaneous abortion (SA) and 18 with unexplained recurrent spontaneous abortion (RSA), were enrolled in the study. A high-resolution spectratyping analysis of fluorescent bands was performed to detect CD28 and CTLA-4 expression in decidual tissues.
The mean expression of CTLA-4 mRNA was significantly higher in women with SA than in controls (P<0.05). Moreover, the expression of CTLA-4 was higher in SA patients with genotype AA and phenotype A+ (AA+AG) than in controls (P<0.01). The expression of CTLA-4 was not significantly different in patients with RSA and in controls. The expression of CD28 was significantly decreased in patients with RSA (P<0.01) and SA (P<0.05) compared with controls. The mean ratios of CTLA-4/CD28 were significantly higher in patients with RSA (P<0.01) and SA (P<0.05) than in controls.
This study suggests that an imbalance in CTLA-4/CD28 expression or suppressed T-cell activity at the maternal-fetal interface may confer susceptibility to unexplained pregnancy loss.
"This strongly suggests that their genes were the direct products of an evolutionarily late duplication event (Harper et al., 1991). It has been shown by RT-PCR study that there was 100% conservation in the amino acid sequence in the local segments of the cytoplasmic tails of the mouse and rat CTLA-4 and 95% overall conservation among these genes in human, mouse and rat (Martin et al., 2000, Wang et al., 2006). Gross and his colleagues (1990) had shown that the murine CD28 clone had 61% nucleotide identity with the human CD28 cDNA and both the murine and human CD28 molecules were integral membrane glycoproteins with a hydrophobic signal peptide sequence and a transmembrane region. "
[Show abstract][Hide abstract] ABSTRACT: The CD28 and CTLA-4 are important co-stimulatory molecules expressed on T cells and regulate T cell activation through antigen stimulation. This study aimed to investigate some properties of these genes and its products; such as the homologous protein sequences to human CTLA-4 and CD28 molecules, the common transcription factor binding sites on their promoters, and phylogenetic relationships of their Immunoglobulin V-Type (IGv) domains using bioinformatical approaches. Our results revealed that both CTLA-4 and CD28 molecules are moderately conserved among all organisms investigated. The IGv domains of human CTLA-4 and CD28 are closest to those of Macaca nemestrina, Cercocebus torquatus atys , Macaca mulatta and Papio cynocephalus anubis . In contrast, the IGv domain of CD28 of Gallus gallus and that of CTLA-4 of Mus musculus and Rattus norvegicus is most apart from those of human, respectively. The comparative screening of the promoters revealed that both CTLA-4 and CD28 genes have some conserved transcription factor binding sites.
[Show abstract][Hide abstract] ABSTRACT: Induction and maintenance of immunologic tolerance in humans remains a desirable but elusive goal. Therefore, understanding the physiologic mechanisms of regulation of immune responses is highly clinically relevant for immune-mediated diseases (e.g., autoimmunity and asthma/allergy) and for cell and organ transplantation. Acceptance of the fetus, which expresses paternally inherited alloantigens, by the mother during pregnancy is a unique example of how the immune system reshapes a destructive alloimmune response to a state of tolerance. Understanding the complex mechanisms of fetomaternal tolerance has important implications for developing novel strategies to induce immunologic tolerance in humans in general and for prevention of spontaneous abortion in at-risk populations in particular.
The Journal of Immunology 04/2007; 178(6):3345-51. DOI:10.4049/jimmunol.178.6.3345 · 4.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to study genetic variability in the gene encoding cytotoxic T-lymphocyte antigen (CTLA-4) and individual susceptibility to the development of preeclampsia or placental abruption.
A total of 361 women (132 with preeclampsia, 117 with placental abruption and 112 healthy controls) were genotyped for 49A-G polymorphism (dbSNP: rs231775) in the CTLA-4 gene.
The frequency of the G alleles was significantly higher in women with preeclampsia than in controls (51.1% vs. 42.0%; OR 1.44, 95% CI 1.01-3.48, p<0.043). Women with placental abruption had decreased frequency of AA genotype (22.2% vs. 35.7%) and significantly more AG or GG genotypes compared with controls (OR 1.94, 95% CI 1.09-2.07, p<0.024). No significant differences were detected in the frequencies of genotype GG (29.5%, 21.4% and 19.6%, respectively) between the three groups.
Our data suggest that the 49A-G polymorphism in the CTLA-4 gene is associated with the development of placental abruption and preeclampsia, with women having the G allele being at risk.
Clinical Chemistry and Laboratory Medicine 02/2008; 46(2):169-73. DOI:10.1515/CCLM.2008.034 · 2.71 Impact Factor
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