@Article{Schubert_Bode_Kenefeck-Autos_domin_immun-2014,
  author =	 {Schubert, Desiree and Bode, Claudia and Kenefeck, Rupert 
                  and Hou, Tie Zheng and Wing, James B. and Kennedy, Alan and 
                  Bulashevska, Alla and Petersen, Britt-Sabina and Schaffer, 
                  Alejandro A. and Gruning, Bjorn A. and Unger, Susanne and 
                  Frede, Natalie and Baumann, Ulrich and Witte, Torsten and 
                  Schmidt, Reinhold E. and Dueckers, Gregor and Niehues, Tim 
                  and Seneviratne, Suranjith and Kanariou, Maria and 
                  Speckmann, Carsten and Ehl, Stephan and Rensing-Ehl, Anne 
                  and Warnatz, Klaus and Rakhmanov, Mirzokhid and Thimme, 
                  Robert and Hasselblatt, Peter and Emmerich, Florian and 
                  Cathomen, Toni and Backofen, Rolf and Fisch, Paul and Seidl, 
                  Maximilian and May, Annette and Schmitt-Graeff, Annette and 
                  Ikemizu, Shinji and Salzer, Ulrich and Franke, Andre and 
                  Sakaguchi, Shimon and Walker, Lucy S. K. and Sansom, David 
                  M. and Grimbacher, Bodo},
  title =	 {Autosomal dominant immune dysregulation syndrome in humans 
                  with {CTLA4} mutations},
  journal =	 {Nat Med},
  year =	 {2014},
  volume =	 {20},
  number =	 {12},
  pages =	 {1410-1416},
  user =	 {kousik},
  pmid =	 {25329329},
  doi = 	 {10.1038/nm.3746},
  issn = 	 {1546-170X},
  issn = 	 {1078-8956},
  abstract =	 {The protein cytotoxic T lymphocyte antigen-4 (CTLA-4) is an 
                  essential negative regulator of immune responses, and its 
                  loss causes fatal autoimmunity in mice. We studied a large 
                  family in which five individuals presented with a complex, 
                  autosomal dominant immune dysregulation syndrome 
                  characterized by hypogammaglobulinemia, recurrent infections 
                  and multiple autoimmune clinical features. We identified a 
                  heterozygous nonsense mutation in exon 1 of CTLA4. Screening 
                  of 71 unrelated patients with comparable clinical phenotypes 
                  identified five additional families (nine individuals) with 
                  previously undescribed splice site and missense mutations in 
                  CTLA4. Clinical penetrance was incomplete (eight adults of a 
                  total of 19 genetically proven CTLA4 mutation carriers were 
                  considered unaffected). However, CTLA-4 protein expression 
                  was decreased in regulatory T cells (Treg cells) in both 
                  patients and carriers with CTLA4 mutations. Whereas Treg 
                  cells were generally present at elevated numbers in these 
                  individuals, their suppressive function, CTLA-4 ligand 
                  binding and transendocytosis of CD80 were impaired. 
                  Mutations in CTLA4 were also associated with decreased 
                  circulating B cell numbers. 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.}
}