Genomes and Genes
Hans D Ochs
Affiliation: University of Washington
- Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cellsTroy R Torgerson
Department of Pediatrics, University of Washington School of Medicine and Children s Hospital and Regional Medical Center, Seattle, Wash, USA
J Allergy Clin Immunol 120:744-50; quiz 751-2. 2007..We are hopeful that the knowledge gained about mechanisms that regulate FOXP3 expression and Treg function will have a major effect on how other autoimmune and allergic disorders are approached...
- Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency diseaseSuzanne Skoda-Smith
Seattle Children s Research Institute and Department of Pediatrics, University of Washington, Seattle, Washington
Ther Clin Risk Manag 6:1-10. 2010..SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life...
- Monitoring serum IL-18 levels is useful for treatment of a patient with systemic juvenile idiopathic arthritis complicated by macrophage activation syndromeTomonari Shigemura
Department of Infection and Host Defense, Shinshu University, Graduate School of Medicine, Matsumoto 390 8621, Japan
Pediatr Rheumatol Online J 9:15. 2011..IL-18 is an extremely useful cytokine for monitoring the activity of sJIA and MAS, and serum IL-18 can be used as an indicator for the effectiveness of treatment and the decision to discontinue therapy...
- FOXP3 acts as a rheostat of the immune responseHans D Ochs
University of Washington and Children s Hospital Regional Medical Center, Seattle, WA, USA
Immunol Rev 203:156-64. 2005....
- Structure and function of the Wiskott-Aldrich syndrome proteinHans D Ochs
Departments of Pediatrics, University of Washington, Seattle, Washington 98109, USA
Curr Opin Hematol 12:284-91. 2005..The responsible gene, WASP, has multiple domains, each with unique functions that were only recently fully recognized...
- Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapyBaowei Peng
Department of Pediatrics, Seattle Children s Research Institute and University of Washington, Seattle, WA 98101, USA
Blood 114:4373-82. 2009..Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice...
- CD4+FOXP3+ regulatory T cells confer long-term regulation of factor VIII-specific immune responses in plasmid-mediated gene therapy-treated hemophilia miceCarol H Miao
Seattle Children s Research Institute, Seattle, WA 98101, USA
Blood 114:4034-44. 2009..Antigen-specific Tregs can provide long-lasting protection against immune responses in vivo and limit recall responses induced by a second challenge via infectious tolerance...
- Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A miceBaowei Peng
Department of Pediatrics, Seattle Children s Hospital Research Institute and University of Washington, Seattle, WA 98101, USA
Blood 112:1662-72. 2008..Our data indicate that transient anti-ICOS monoclonal antibody treatment represents a novel single-agent immunomodulatory strategy to overcome the immune responses against transgene product after gene therapy...
- Stable hematopoietic cell engraftment after low-intensity nonmyeloablative conditioning in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndromeLAURI M BURROUGHS
Fred Hutchinson Cancer Research Center, Seattle, Wash 98109 1024, USA
J Allergy Clin Immunol 126:1000-5. 2010..Hematopoietic cell transplantation is currently the only viable option for long-term survival, but patients are frequently very ill and may not tolerate traditional myeloablative conditioning regimens...
- IPEX, FOXP3 and regulatory T-cells: a model for autoimmunityHans D Ochs
Division of Immunology, Infectious Diseases, Rheumatology, Children s Hospital and University of Washington, 307 Westlake Ave North, Suite 300 CW, Seattle, WA 98109, USA
Immunol Res 38:112-21. 2007....
- Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndromeWen I Lee
Department of Pediatrics, University of Washington, School of Medicine, Children s Hospital and Regional Medical Center, 307 Westlake Ave N, Suite 300, Seattle, WA 98109, USA
Blood 105:1881-90. 2005....
- Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndromeAlexander Astrakhan
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98101, USA
Blood 119:4395-407. 2012..Our findings identify the advantages and disadvantages associated with each vector and suggest further clinical development of the MND-huWASp LV for a future clinical trial for WAS...
- Immune dysregulation, polyendocrinopathy, enteropathy, X-linked inheritance: model for autoaggressionHans D Ochs
University of Washington, Seattle, WA, USA
Adv Exp Med Biol 601:27-36. 2007..Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation...
- Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressorJared E Lopes
Benaroya Research Institute, Virginia Mason, Seattle, WA 98101, USA
J Immunol 177:3133-42. 2006..Furthermore, we demonstrate that IPEX mutations in these domains correlate with deficiencies in FOXP3 repressor function, corroborating their in vivo relevance...
- X-linked immunodeficienciesHans D Ochs
Department of Pediatrics, University of Washington, Children s Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA 98105, USA
Curr Allergy Asthma Rep 4:339-48. 2004..Additionally, gene therapy has been attempted in X-linked severe combined immune deficiency (XSCID), with clear evidence of successful correction of the pathology, and the appearance of severe adverse effects...
- Wiskott-Aldrich syndrome protein is required for homeostasis and function of invariant NKT cellsAlexander Astrakhan
Department of Immunology, University of Washington School of Medicine and Seattle Children s Research Institute, Seattle, WA 98101, USA
J Immunol 182:7370-80. 2009..Our findings highlight the crucial role for WASp in iNKT development, homeostasis, and activation, and identify iNKT dysfunction as an additional factor likely to contribute to the clinical features observed in WAS patients...
- Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 geneTroy R Torgerson
University of Washington and Children s Hospital, Department of Pediatrics, Division of Immunology, Rheumatology, and Infectious Diseases, Seattle, Washington, USA
Gastroenterology 132:1705-17. 2007..In the present work, we aimed to uncover the molecular basis of a distinct form of IPEX syndrome presenting at the edge of autoimmunity and severe allergy...
- Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlationYinZhu Jin
Department of Pediatrics, University of Washington, Seattle, WA 98109, USA
Blood 104:4010-9. 2004..By analyzing a large number of patients with WAS/XLT at the molecular level we identified 5 mutational hotspots in the WASP gene and have been able to establish a strong association between genotype and phenotype...
- Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasisEleonora Gambineri
Department of Pediatrics, Division of Immunology, Rheumatology and Infectious Diseases, University of Washington, Seattle, Washington, USA, and Department of Pediatrics, A Meyer Children s Hospital, University of Florence, Florence, Italy
Curr Opin Rheumatol 15:430-5. 2003..This review describes the clinical features of IPEX and the structure, function, and known mutations of FOXP3 that provide important insights into its role in maintenance of immune homeostasis...
- Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell developmentMarc A Gavin
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 103:6659-64. 2006..This observation raises the possibility that the severe autoimmunity in FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that have developed from T(R) precursors...
- Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A miceCarol H Miao
Children s Hospital and Regional Medical Center, Department of Pediatrics, University of Washington, Seattle, WA 98109, USA
Blood 108:19-27. 2006....
- Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patientPing Liu
Department of Pediatrics, University of Washington and Seattle Children s Hospital Research Institute, Seattle, WA, USA
Clin Immunol 130:162-74. 2009....
- Patients with abnormal IgM levels: assessment, clinical interpretation, and treatmentHans D Ochs
Department of Pediatrics, University of Washington School of Medicine, Children s Hospital and Regional Medical Center, Seattle Children s Hospital Research Institute, Seattle, Washington 98101, USA
Ann Allergy Asthma Immunol 100:509-11. 2008
- FOXP3 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expressionTroy R Torgerson
Department of Pediatrics, University of Washington School of Medicine and Children s Hospital, Seattle, WA 98109, USA
J Immunol 183:907-15. 2009....
- A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathyLena F Schimke
Department of Pediatrics, University of Washington and Seattle Children s Research Institute, Seattle, WA 98101 1304, USA
J Clin Immunol 33:1088-99. 2013..M37K substitution affects NF-κB activation by interfering with IκB-α degradation, thus impairing NF-κB signaling and causing the EDA-ID phenotype...
- Regulatory T cells in primary immunodeficiency diseasesTroy R Torgerson
Division of Pediatric Immunology, Rheumatology and Infectious Diseases, University of Washington School of Medicine, Children s Hospital, Seattle, Washington, USA
Curr Opin Allergy Clin Immunol 7:515-21. 2007..Here, we review the role of regulatory T-cell deficits in mediating the immune dysregulation associated with certain primary immune deficiency disorder syndromes...
- The Wiskott-Aldrich syndromeHans D Ochs
University of Washington, School of Medicine, Seattle 98195, USA
J Allergy Clin Immunol 117:725-38; quiz 739. 2006....
- TH17 cells and regulatory T cells in primary immunodeficiency diseasesHans D Ochs
Department of Pediatrics, University of Washington School of Medicine and Seattle Children s Hospital, Seattle, Wash 98101, USA
J Allergy Clin Immunol 123:977-83; quiz 984-5. 2009..These observations emphasize the importance of functionally distinct T-cell lineages in maintaining a balanced innate and cognate immune system...
- Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: a model of immune dysregulationTroy R Torgerson
Department of Pediatrics, University of Washington School of Medicine and Children s Hospital Regional Medical Center, Seattle, 98195, USA
Curr Opin Allergy Clin Immunol 2:481-7. 2002..We examine therapeutic options to treat the syndrome, study its immunologic basis, and investigate the structure and function of the FOXP3 protein...
- Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypesHans D Ochs
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
Immunol Res 44:84-8. 2009..However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression...
- Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseasesHans D Ochs
Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98107, USA
J Clin Immunol 26:265-73. 2006..No treatment-related serious adverse events were reported. We conclude that subcutaneous administration of 16% SCIg is a safe and effective alternative to IVIg for replacement therapy of PIDD...
- Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatmentHans D Ochs
Department of Pediatrics, University of Washington, Seattle, Washington, USA
Biol Blood Marrow Transplant 15:84-90. 2009..The issue of whether mixed chimerism post-HCT (which has a higher incidence in RIC transplantation) is associated with increased autoimmune manifestations in patients with WAS remains to be resolved...
- Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndromeMichael H Albert
aDepartment of Pediatric Hematology Oncology, Dr von Haunersches Kinderspital der Ludwig Maximilians Universität, Munich, Germany bThe Manton Center for Orphan Disease Research and the Division of Immunology, Children s Hospital, Harvard Medical School, Boston, Massachusetts, USA cDepartment of Pediatrics, University of Washington, and Seattle Children s Research Institute, Center for Immunity and Immunotherapy, Seattle, Washington, USA
Curr Opin Hematol 18:42-8. 2011..This review focuses on recent developments in the understanding of its basic pathophysiology, diverse clinical phenotypes and optimal patient management including novel therapies...
- History of primary immunodeficiency diseasesHans D Ochs
Department of Pediatrics, University of Washington School of Medicine and Seattle Children s Research Institute, Seattle, Washington 98101, USA
Curr Opin Allergy Clin Immunol 12:577-87. 2012....
- The Wiskott-Aldrich syndromeHans D Ochs
Department of Pediatrics, and Division of Immunology, Infectious Disease and Rheumatology, University of Washington School of Medicine, Seattle, WA, USA
Isr Med Assoc J 4:379-84. 2002
- Inducible CO-stimulator molecule, a candidate gene for defective isotype switching, is normal in patients with hyper-IgM syndrome of unknown molecular diagnosisWen I Lee
School of Medicine, University of Washington, Seattle 98195 6320, USA
J Allergy Clin Immunol 112:958-64. 2003..In a substantial subgroup of HIGM patients, these 4 genes are normal, and the genetic defect is unknown...
- Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndromeDavid S Nieves
Department of Dermatology, University of Rochester, Rochester, NY, USA
Arch Dermatol 140:466-72. 2004..If untreated, affected males die early in life from malabsorption and other complications. To our knowledge, this syndrome has never been described in the dermatology literature...
- The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappa B (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangementWinifred Huang
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, New York, NY 10021, USA
J Immunol 174:2602-11. 2005..Our results indicate that WASp independently regulates its dual functions, i.e., actin cytoskeletal remodeling and transcription in NK cells...
- WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotypeKohsuke Imai
INSERM The French Institute of Health and Medical Research U429, Hopital Necker Enfants Malades, Paris, France
Curr Opin Allergy Clin Immunol 3:427-36. 2003..In this review we will focus on recent molecular findings that provide a better understanding of the pathogenesis of this complex disease and explore the correlation of genotype and clinical phenotype...
- Missense mutations of the WASP gene cause intermittent X-linked thrombocytopeniaLucia D Notarangelo
Department of Pediatrics, Istituto di Medicina Molecolare Angelo Nocivelli, University of Brescia, Spedali Civili, 25123 Brescia, Italy
Blood 99:2268-9. 2002..This observation broadens the spectrum of clinical phenotypes associated with WASP gene defects, and it indicates the need for molecular analysis in males with reduced platelet volume, regardless of the platelet number...
- Clinical course of patients with WASP gene mutationsKohsuke Imai
Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1 5 45, Yushima, Bunkyo ku, Tokyo, 113 8519, Japan
Blood 103:456-64. 2004..Based on data presented here, hematopoietic stem cell transplantation should be considered, especially for WASP-negative patients, while the patients are young to improve prognosis...
- A potential screening tool for IPEX syndromeMeredith Lee Heltzer
Division of Allergy and Immunology, Department of Pediatrics, University of Pennsylvania School of Medicine, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
Pediatr Dev Pathol 10:98-105. 2007..This screening test provides a valuable tool for diagnosing IPEX syndrome in extremely ill patients who may not tolerate a delay in therapeutic intervention...
- [X-linked hyper-IGM syndrome associated to sclerosing cholangitis and gallbladder neoplasm: clinical case]Cristián Rodríguez
Laboratorio de Inmunologia, Facultad de Medicina, Universidad de Los Andes, San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile
Rev Med Chil 131:303-8. 2003..Three years after diagnosis, we detected the presence of polyps inside the gallbladder that were reported at biopsy as adenocarcinoma. He underwent hepatic bisegmentectomy (VI B-V) and local lymphadenectomy...
- Absence of memory B cells in patients with common variable immunodeficiencyKazunaga Agematsu
Department of Infectious Immunology, Graduate School of Medicine, Matsumoto, Shinshu University, Japan
Clin Immunol 103:34-42. 2002....
- WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP)Miguel A de la Fuente
Division of Immunology, Children s Hospital Boston, One Blackfan Circle, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:926-31. 2007..These results demonstrate that WIP stabilizes WASP and suggest that it may also be important for its function...
- WAVE/Scars in plateletsAtsushi Oda
Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Kitaku, Sapporo, 060 8638, Japan
Blood 105:3141-8. 2005..These data suggest that the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets...
- Wiskott-Aldrich Syndrome: a model for defective actin reorganization, cell trafficking and synapse formationLuigi D Notarangelo
Department of Pediatrics, University of Brescia, Spedali Civili, 25123 Brescia
Curr Opin Immunol 15:585-91. 2003..Mutation analysis of large cohorts of WAS/X-linked thrombocytopenia patients has provided evidence for a strong correlation between phenotype and genotype...
- X-linked agammaglobulinemia in northern ThailandMuthita Trakultivakorn
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Asian Pac J Allergy Immunol 24:57-63. 2006..One patient died of sepsis at the age of 16 years. These observations demonstrate that early diagnosis and treatment can improve prognosis and quality of life...
- CD40 ligand and MHC class II expression are essential for human peripheral B cell toleranceMaxime Hervé
Laboratory of Biochemistry and Molecular Immunology, Hospital for Special Surgery, New York, NY 10021, USA
J Exp Med 204:1583-93. 2007..The decreased frequency of MHC class II-restricted CD4(+) regulatory T cells in CD40L-deficient patients suggests that these T cells may mediate peripheral B cell tolerance through CD40L-CD40 and MHC class II-TCR interactions...
- X-linked agammaglobulinemia: report on a United States registry of 201 patientsJerry A Winkelstein
United States Immune Deficiency Network, Immune Deficiency Foundation, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Medicine (Baltimore) 85:193-202. 2006....
- Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L, and DRP2 genesAnna Sediva
Institute of Immunology, University Hospital Motol, V Uvalu 84, 150 06, Prague 5, Czech Republic
J Clin Immunol 27:640-6. 2007..The severity of symptoms, however, did not correlate with the extent of the deletion...
- Developmental changes of FOXP3-expressing CD4+CD25+ regulatory T cells and their impairment in patients with FOXP3 gene mutationsTatsuya Fuchizawa
Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama 930 0194, Japan
Clin Immunol 125:237-46. 2007..This observation suggests a possible genotype-phenotype correlation in IPEX...
- WASP and the phenotypic range associated with deficiencyLuigi D Notarangelo
Department of Pediatrics and Angelo Nocivelli Institute for Molecular Medicine, University of Brescia, Spedali Civili, Brescia, Italy
Curr Opin Allergy Clin Immunol 5:485-90. 2005..Advances in preclinical models of gene therapy for WAS are presented...
- STAT3 mutation in the original patient with Job's syndromeEllen D Renner
N Engl J Med 357:1667-8. 2007
- Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome)Lutz Bindl
Children s Hospital Medical Center, University of Bonn, Germany
J Pediatr 147:256-9. 2005..We report the successful use of sirolimus in 3 patients with IPEX. The efficacy of sirolimus is probably due to its different mode of action compared to calcineurin-dependent agents...
- Wiskott-Aldrich syndromeLuigi D Notarangelo
Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA, USA
Curr Opin Hematol 15:30-6. 2008..This review will focus on recent progress in understanding the molecular basis of Wiskott-Aldrich syndrome and its ramifications for the cure of this lethal disease...
- Familial hemophagocytic lymphohistiocytosis in two brothers with X-linked agammaglobulinemiaKris Ann P Schultz
Division of Hematology Oncology and Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
Pediatr Blood Cancer 51:293-5. 2008..Further studies revealed absence of Bruton's tyrosine kinase (BTK) protein expression and a novel BTK mutation...
- Effect of therapeutic integrin (CD11a) blockade with efalizumab on immune responses to model antigens in humans: results of a randomized, single blind studyJames G Krueger
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York 10065, USA
J Invest Dermatol 128:2615-24. 2008..These results expand our knowledge of how immune responses are modulated in humans by CD11a blockade and have implications for vaccinations of patients treated with this agent...
- Restricted immunoglobulin constant heavy G chain genes in primary immunodeficienciesVivi Anne Oxelius
Department of Pediatrics and Institute of Clinical Immunology, University Hospital, Lund University, SE 221 85 Lund, Sweden
Clin Immunol 128:190-8. 2008..3 and OR 2.8 respectively). Restricted IGHG genes, restricted IgG allotypes (Fc domains) and restricted B cells are significant in PIDs for diagnosis, treatment and pathogenetic mechanisms...
- Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacementAlessandro Aiuti
Nat Med 8:423-5. 2002