These data suggest that high expression of Fas, FasL and IL-6 and low expression of CTLA-4 by the CD8<sup>+</sup>CD28<sup>+</sup> T-cell subset promotes the activation-induced cell death of the CD8<sup>+</sup>CD28<sup>+</sup> T-cell subset, resulting in an imbalance of CD8<sup>+</sup>CD28<sup>-</sup>/CD8<sup>+</sup>CD28<sup>+</sup> T cells in active SLE patients, which represents an important feature in the immunological pathogenesis of SLE.
In the present study, interleukin (IL)-10-treated DCs and CTLA4-Ig were administered to mice with SLE alone or in combination and the therapeutic effects were investigated.
In conclusion, our findings showed, that there is an association between systemic inflammatory markers, oxidative stress and the CTLA-4G-1661A GG+AG genotypes, MDA and neopterin which are the most conventional risk factors for coronary heart disease, therefore these mutations may be consider as a risk factor for susceptibility to heart disease in SLE patients.
The programmed cell death 1 gene (PDCD1), the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene, and the methyl-CpG-binding protein 2 gene (MECP2) are considered to be the candidate genes associated with SLE.
We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese).
We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese).
Further investigations are required to identify whether other at-risk polymorphisms within CTLA-4 confer a risk of SLE and to clarify the role of the CTLA-4 gene.
Our results suggest that the -1661AG and -1722TC polymorphisms in the promoter region of the CTLA-4 gene does not play any role in genetic susceptibility to SLE.
We found the first evidence of genetic association between lupus in African American patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and CTLA4; P = 8.0 × 10⁻⁶, P = 1.9 × 10⁻⁵, P = 5.7 × 10⁻⁵, P = 0.00099, and P = 0.0045, respectively).
The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015).
Disorders of the CTLA-4 gene, especially a GG genotype in exon 1 at +49 and/or 106-bp fragment length of the 3'UTR in exon 4, may be involved in early development of SLE in Japanese children, such as the boys described here.
Multiple investigators have examined patient cohorts gathered from around the world, and although we doubt that all of the reported associations will be replicated, we have probably already discovered many of the genes that are important in lupus pathogenesis, including those encoding human leukocyte antigen-DR, Fcgamma receptor 3A, protein tyrosine phosphatase nonreceptor 22, cytotoxic T lymphocyte associated antigen 4, and mannose-binding lectin.