Genetic variants of apoptotic pathway-related factors (including PDCD1, PDCD1LG2, FAS, and FASLG) may affect apoptosis and in turn predict susceptibility to autoimmune disease.
The discovery that they are mutated in the fasl and the fas receptor gene, respectively, demonstrates the critical role of the FasL/Fas system in lymphocyte homeostasis and autoimmunity.
We also generated biotinyl- and palmitoyl-labelled peptidomimetics, useful chemico-biological tools to further explore the pro-inflammatory signal of CD95, which plays an important role in the pathogenesis of lupus and other autoimmune diseases.
Moreover, altered expression of CD95 or its ligand causes autoimmunity and has also been directly involved in recurrent pregnancy losses and pregnancy disorders.
FAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities.
Autoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity.
Increased activation of CD95/Fas by Fas ligand in viral hepatitis and autoimmunity is involved in pathogenesis of fulminant hepatitis and liver failure.
Retro-transposon insertion into the second intron of the pro-apoptotic Fas gene appears to be responsible for both lymphoproliferation and autoimmunity, while other genes are more likely to contribute to the regenerative healing characteristic of this mouse strain.
Autoimmune lymphoproliferative syndrome (ALPS) is a well-characterized pediatric autoimmune disease caused by mutations in genes associated with the FAS-dependent apoptosis pathway.
CD95 (Fas-ligand) is a key mediator of cell death in multiple setting, thus its loss within the MRL-lpr (Fas<sup>lpr</sup>) homozygote mice results in spontaneous autoimmunity.
Our data uncover a defect in B-cell selection in patients with FAS mutations, which has implications for the understanding of the pathogenesis of autoimmunity and lymphomagenesis of autoimmune lymphoproliferative syndrome.
FAS and FAS ligand (FASLG) are important proapoptotic proteins that have a significant function in regulating cell growth and apoptosis and play essential roles in many human autoimmune diseases.
Although it has not yet been possible to assign any particular allele or genotype to the control of FAS expression, this polymorphism has been described to be associated with several autoimmune diseases including LE.
The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity.
The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity.
Inherited and acquired defects in the Fas gene, TNFRSF6 (tumor necrosis factor receptor superfamily member 6) have been associated with human autoimmune lymphoproliferative syndrome (ALPS) and a spectrum of other complex autoimmune diseases and malignancies.
Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity.
Due to the functional relevance of the Fas pathway in autoimmune thyroid disease we were interested in the possible contribution of polymorphisms in the Fas gene to the genetic risk of thyroid autoimmunity, which so far is mainly, but incompletely, attributed to the HLA DQ region and polymorphisms in the CTLA-4 gene.
Hence, as has been demonstrated for CD95-deficient mice, also GC-derived autoreactive B cells carrying somatic CD95 gene mutations may potentially service negative selection and participate in the development of autoimmune diseases.