Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease.

Wu, Jiang; Wilson, Janet E.; He, Jin; Xiang, Leihong; Schur, Peter H.; Mountz, John D.

doi:10.1172/jci118892

Cited by 434 publications

(224 citation statements)

References 34 publications

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“…Both the receptor and its ligand are candidate contributory genes in SLE, as mutations in either of these genes result in autoimmunity in mouse models of SLE. 16,17 Expression of FasL was decreased in the overnight samples relative to the fresh samples. Fasassociated via death domain (FADD), an important adaptor protein in the signaling pathway downstream Figure 3 Functional classification of selected genes whose expression is sensitive to overnight ex vivo incubation of blood.…”

Section: Resultsmentioning

confidence: 96%

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

et al. 2004

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Section: Resultsmentioning

confidence: 96%

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

et al. 2004

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“…That is, in addition to the association between genetic defects in Fas or Fas ligand and autoimmunity in mice (40)(41)(42)(43)(44)(45)(46)(47) and humans (48)(49)(50)(51), non-Fas-based abnormalities may play paramount roles in the pathogenesis and/or perpetuation of SLE.…”

Section: Discussionmentioning

confidence: 99%

Impaired nonrestricted cytolytic activity in systemic lupus erythematosus

Stohl

Elliott

et al. 1997

Arthritis & Rheumatism

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Objective. To determine the cytolytic effector pathway involved in impaired generation of nonrestricted cytolytic activity in systemic lupus erythemato- sus (SLE).Methods. Peripheral blood mononuclear cells (PBMC) from normal subjects and SLE patients were stimulated in vitro with anti-CD3 monoclonal antibody (MAb) and interleukin-2 to promote the generation of nonrestricted cytolytic activity. On day 13 of culture, the PBMC were assayed for cytolytic activity against FasDaudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium chelation, antagonist anti-Fas MAb, tumor necrosis factor (TNF) a and P, and ATP were measured. Intracellular perforin expression was determined by intracellular staining, and perforin messenger RNA levels were determined by quantitative competitive reverse transcription-polymerase chain reaction.Results. We demonstrated the existence of a cytolytic pathway that is independent of Fas, TNFa, TNFP, and ATP, but is dependent upon extracellular calcium. Despite its calcium dependence, this pathway is associated with low-to-undetectable levels of perforin.Conclusion. Impaired generation of nonrestricted ~-cytolytic activity in SLE is likely due to decreased activity of this Fas-, TNFa-, TNFP-, ATP-independent pathway associated with very low levels of perforin.

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“…110 Several studies have evaluated the possible association between SLE and a structural mutation in the FASL gene. 111 113 This protein plays two crucial roles in host protection against pathogens: (1) MBL-targets are phagocytosed after direct interaction between the target and the MBL receptors (one of which is the C1qR P receptor, a C1q/MBL/surfactant protein A receptor the mediates enhanced phagocytosis 114 ), and (2) through triggering its MBL-associated serine proteases (MASP-1 and MASP-2), MBL is capable of activating the classical complement pathway. [114][115][116] Three single nucleotide polymorphisms are located in the structural region of the gene at codons 52, 54 and 57, and two are in the promoter region at −550H/L and −221X/Y.…”

Section: Fas and Fas Ligandmentioning

confidence: 99%