Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

Bollain-y-Goytia, Juan José; Arellano-Rodríguez, Mariela; Torres-del-Muro, Felipe; Daza-Benítez, Leonel; Muñoz‐Valle, José Francisco; Avalos‐Díaz, Esperanza; Herrera‐Esparza, Rafael

doi:10.1155/2014/780406

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…Variants of genes that encode for both the death receptor Fas and its ligand, FasL, are associated with the pathogenesis of SLE, with the -670 FAS polymorphism directly linked to development of LN [111, 112]. …”

Section: Programmed Cell Death Pathways In Dendritic Cells and Macmentioning

confidence: 99%

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

Tsai

Perlman

Cuda

2017

Clinical Immunology

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Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission.

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Section: Programmed Cell Death Pathways In Dendritic Cells and Macmentioning

confidence: 99%

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

Tsai

Perlman

Cuda

2017

Clinical Immunology

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“…However, despite that Fas/CD95 is present in most MM cell lines and malignant cells derived from myeloma patients, several clones of myeloma cells are resistant to undergo apoptosis when challenged with agonistic anti-Fas/ CD95 antibody [92][93][94][95]. A functional Fas/CD95 promoter polymorphism (2670 FAS promoter A/G polymorphism; STAT1-binding site) has been associated with susceptibility, clinical manifestation, and survival in adult T cell leukemia [96] and with genetic susceptibility in systemic lupus erythematosus patients with elevated levels of soluble Fas/CD95 in lupus nephritis with proteinuria [97].…”

Section: Fas/cd95 In the Regulation Of Apoptosis In Hematologic Cellsmentioning

confidence: 99%

Lipid raft-mediated Fas/CD95 apoptotic signaling in leukemic cells and normal leukocytes and therapeutic implications

Gajate

Mollinedo

2015

Journal of Leukocyte Biology

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Plasma membrane is now recognized to contain tightly packed cholesterol/sphingolipid-rich domains, known as lipid or membrane rafts, which are more ordered than the surrounding lipid bilayer. Lipid rafts are crucial for the compartmentalization of signaling processes in the membrane, mostly involved in cell survival and immune response. However, in the last 15 years, a large body of evidence has also identified raft platforms as scaffolds for the recruitment and clustering of death receptor Fas/CD95 and downstream signaling molecules, leading to the concept of death-promoting lipid rafts. This raft-Fas/CD95 coclustering was first described at the early 2000s as the underlying mechanism for the proapoptotic action of the alkylphospholipid analog edelfosine in leukemic cells, hence facilitating protein-protein interactions and conveying apoptotic signals independently of Fas/CD95 ligand. Edelfosine induces apoptosis in hematologic cancer cells and activated T-lymphocytes. Fas/CD95 raft coclustering is also promoted by Fas/CD95 ligand, agonistic Fas/CD95 antibodies, and additional antitumor drugs. Thus, death receptor recruitment in rafts is a physiologic process leading to cell demise that can be pharmacologically modulated. This redistribution and local accumulation of apoptotic molecules in membrane rafts, which are usually accompanied by displacement of survival signaling molecules, highlight how alterations in the apoptosis/survival signaling balance in specialized membrane regions modulate cell fate. Membrane rafts might also modulate apoptotic and nonapoptotic death receptor signaling. Here, we discuss the role of lipid rafts in Fas/CD95-mediated apoptotic cell signaling in hematologic cancer cells and normal leukocytes, with a special emphasis on their involvement as putative therapeutic targets in cancer and autoimmune diseases.

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“…DNA damage) factors, downstream activation of caspases leads to changes in the plasma membrane and chromatin structure, causing the cell to disintegrate into apoptotic blebs. 4 Variants of genes encoding Fas 6 and its ligand, FasL, 7 are linked to SLE pathogenesis, with the −670 FAS polymorphism being linked to LN. 6 DNase1 activity in the intrinsic apoptotic pathway is increased in SLE patients with nephropathy, 8 and polymorphisms in the DNASE1 gene have been linked to LN.…”

Section: Extrarenal Etiologymentioning

confidence: 99%

Genetics of Lupus Nephritis: Clinical Implications

Munroe

James

2015

Seminars in Nephrology

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease marked by the presence of pathogenic autoantibodies, immune dysregulation, and chronic inflammation that may lead to increased morbidity and early mortality from end-organ damage. Over half of all SLE patients will develop lupus nephritis. Genetic association studies have identified more than fifty polymorphisms that contribute to lupus nephritis pathogenesis, including genetic variants associated with altered programmed cell death (PCD) and defective immune clearance of PCD debris. These variants may support the generation of autoantibody-containing immune complexes that contribute to lupus nephritis. Genetic variants associated with lupus nephritis also affect the initial phase of innate immunity and the amplifying, adaptive phase of the immune response. Finally, genetic variants associated with the kidney-specific effector response may influence end-organ damage and the progression to end-stage renal disease and death. This review discusses genetic insights of key pathogenic processes and pathways that may lead to lupus nephritis, as well as the clinical implications of these findings as they apply to recent advances in biologic therapies.

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Soluble Fas and the −670 Polymorphism of Fas in Lupus Nephritis

Cited by 6 publications

References 45 publications

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis

Lipid raft-mediated Fas/CD95 apoptotic signaling in leukemic cells and normal leukocytes and therapeutic implications

Genetics of Lupus Nephritis: Clinical Implications

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