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Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation

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Abstract
Autoimmune diseases develop m approximately 5% of humans They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved m lymphocyte activation, survival, or death For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects m self-tolerance checkpoints as a consequence of mutations m the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6, also known as FAS) However, some mutation carriers remain asymptomatic throughout life We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele Analysis of the patients' CD4(-)CD8(-) (double negative) T cells accumulation of which is a hallmark of ALPS revealed that m these cells, 3 patients had somatic mutations m their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10 This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases
Keywords
INTERLEUKIN-10, FAMILIES, DISEASE, LYMPHOCYTE APOPTOSIS, FEATURES, EXPRESSION, T-CELLS, SOMATIC FAS MUTATIONS

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Citation

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MLA
Magerus-Chatinet, Aude, Bénédicte Neven, Marie-Claude Stolzenberg, et al. “Onset of Autoimmune Lymphoproliferative Syndrome (ALPS) in Humans as a Consequence of Genetic Defect Accumulation.” JOURNAL OF CLINICAL INVESTIGATION 121.1 (2011): 106–112. Print.
APA
Magerus-Chatinet, A., Neven, B., Stolzenberg, M.-C., Daussy, C., Arkwright, P. D., Lanzarotti, N., Schaffner, C., et al. (2011). Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation. JOURNAL OF CLINICAL INVESTIGATION, 121(1), 106–112.
Chicago author-date
Magerus-Chatinet, Aude, Bénédicte Neven, Marie-Claude Stolzenberg, Cécile Daussy, Peter D Arkwright, Nina Lanzarotti, Catherine Schaffner, et al. 2011. “Onset of Autoimmune Lymphoproliferative Syndrome (ALPS) in Humans as a Consequence of Genetic Defect Accumulation.” Journal of Clinical Investigation 121 (1): 106–112.
Chicago author-date (all authors)
Magerus-Chatinet, Aude, Bénédicte Neven, Marie-Claude Stolzenberg, Cécile Daussy, Peter D Arkwright, Nina Lanzarotti, Catherine Schaffner, Sophie Cluet-Dennetiere, Filomeen Haerynck, Gérard Michel, Christine Bole-Feysot, Mohammed Zarhrate, Isabelle Radford-Weiss, Serge P Romana, Capucine Picard, Alain Fischer, and Frédéric Rieux-Laucat. 2011. “Onset of Autoimmune Lymphoproliferative Syndrome (ALPS) in Humans as a Consequence of Genetic Defect Accumulation.” Journal of Clinical Investigation 121 (1): 106–112.
Vancouver
1.
Magerus-Chatinet A, Neven B, Stolzenberg M-C, Daussy C, Arkwright PD, Lanzarotti N, et al. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation. JOURNAL OF CLINICAL INVESTIGATION. 2011;121(1):106–12.
IEEE
[1]
A. Magerus-Chatinet et al., “Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation,” JOURNAL OF CLINICAL INVESTIGATION, vol. 121, no. 1, pp. 106–112, 2011.
@article{5824525,
  abstract     = {Autoimmune diseases develop m approximately 5% of humans They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved m lymphocyte activation, survival, or death For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects m self-tolerance checkpoints as a consequence of mutations m the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6, also known as FAS) However, some mutation carriers remain asymptomatic throughout life We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele Analysis of the patients' CD4(-)CD8(-) (double negative) T cells accumulation of which is a hallmark of ALPS revealed that m these cells, 3 patients had somatic mutations m their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10 This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases},
  author       = {Magerus-Chatinet, Aude and Neven, Bénédicte and Stolzenberg, Marie-Claude and Daussy, Cécile and Arkwright, Peter D and Lanzarotti, Nina and Schaffner, Catherine and Cluet-Dennetiere, Sophie and Haerynck, Filomeen and Michel, Gérard and Bole-Feysot, Christine and Zarhrate, Mohammed and Radford-Weiss, Isabelle and Romana, Serge P and Picard, Capucine and Fischer, Alain and Rieux-Laucat, Frédéric},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keywords     = {INTERLEUKIN-10,FAMILIES,DISEASE,LYMPHOCYTE APOPTOSIS,FEATURES,EXPRESSION,T-CELLS,SOMATIC FAS MUTATIONS},
  language     = {eng},
  number       = {1},
  pages        = {106--112},
  title        = {Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation},
  url          = {http://dx.doi.org/10.1172/JCI43752},
  volume       = {121},
  year         = {2011},
}

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