title: Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.
abstract: The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093; Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, CA 92093;
authors: Brigid S
authors: BS
authors: Boland
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Christella E
authors: CE
authors: Widjaja
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Asoka
authors: A
authors: Banno
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Bing
authors: B
authors: Zhang
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Stephanie H
authors: SH
authors: Kim
authors: Department of Medicine, Mayo Clinic, Rochester, MN 55905;
authors: Samantha
authors: S
authors: Stoven
authors: Western Washington Pathology and Multicare Health System, Tacoma, WA 98405;
authors: Michael R
authors: MR
authors: Peterson
authors: Department of Pediatrics and Rady Children's Hospital, University of California San Diego, La Jolla, CA 92093;
authors: Marilyn C
authors: MC
authors: Jones
authors: Department of Reproductive Medicine, University of California San Diego, La Jolla, CA 92093;
authors: H Irene
authors: HI
authors: Su
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Sheila E
authors: SE
authors: Crowe
authors: Department of Pathology, University of California San Diego, La Jolla, CA 92093;
authors: Jack D
authors: JD
authors: Bui
authors: Department of Pathology, University of California San Diego, La Jolla, CA 92093;
authors: Samuel B
authors: SB
authors: Ho
authors: Center for Gastrointestinal Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75246; Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246;
authors: Yoshinaga
authors: Y
authors: Okugawa
authors: Center for Gastrointestinal Research, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75246; Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246;
authors: Ajay
authors: A
authors: Goel
authors: Department of Medicine, Mayo Clinic, Rochester, MN 55905;
authors: Eric V
authors: EV
authors: Marietta
authors: Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Mahdieh
authors: M
authors: Khosroheidari
authors: Institute of Genomic Medicine, University of California San Diego, La Jolla, CA 92093;
authors: Kristen
authors: K
authors: Jepsen
authors: Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona 08003 Spain; and.
authors: Jose
authors: J
authors: Aramburu
authors: Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona 08003 Spain; and.
authors: Cristina
authors: C
authors: López-Rodríguez
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093; Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, CA 92093;
authors: William J
authors: WJ
authors: Sandborn
authors: Department of Medicine, Mayo Clinic, Rochester, MN 55905;
authors: Joseph A
authors: JA
authors: Murray
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093.
authors: Olivier
authors: O
authors: Harismendy
authors: Department of Medicine, University of California San Diego, La Jolla, CA 92093; Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, CA 92093; changj@ucsd.edu.
authors: John T
authors: JT
authors: Chang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004252:DNA Mutational Analysis; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D057895:Haploinsufficiency / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C118125:NFAT5 protein, human; D014157:Transcription Factors