Here we compare three different patient groups with disturbances in the CTLA-4 pathway-CTLA-4-haploinsufficiency, LRBA-deficiency, and ipilimumab-treated melanoma patients.
Although their clinical phenotype, multi-organ inflammatory disease, is superficially similar to that of CTLA4 haploinsufficient autoimmune lymphoproliferative syndrome type V (ALPS5) patients, we demonstrate our subjects' underlying immunopathology to be distinct.
We make a risky but testable prediction: anti-CTLA-4 therapy may have mechanism similar to that occurring in inherited human CTLA-4 haploinsufficiency.
Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.
Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs.
Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.
Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.
Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs.
Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs.
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.