title: Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders.
abstract: Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGFβ) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations.
authors: Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Center of Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: kerstin.felgentreff@childrens.harvard.edu.
authors: Kerstin
authors: K
authors: Felgentreff
authors: University Heart Center Freiburg Bad Krozingen, Freiburg, Germany.
authors: Matthias
authors: M
authors: Siepe
authors: Department of Pediatric Cardiology, University Hospital Münster, Münster, Germany.
authors: Stefan
authors: S
authors: Kotthoff
authors: University Heart Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Yskert
authors: Y
authors: von Kodolitsch
authors: Center of Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany.
authors: Kristina
authors: K
authors: Schachtrup
authors: Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Luigi D
authors: LD
authors: Notarangelo
authors: Division of Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA.
authors: Jolan E
authors: JE
authors: Walter
authors: Center of Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany. Electronic address: stephan.ehl@uniklinik-freiburg.de.
authors: Stephan
authors: S
authors: Ehl
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003240:Connective Tissue Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004485:Eczema / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007589:Job Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology; D055947:Loeys-Dietz Syndrome / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D020125:Mutation, Missense; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D016207:Cytokines; D018125:Receptors, Transforming Growth Factor beta; D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human
keywords: Allergy; EBV; EDS; Eczema; Ehlers–Danlos syndrome; Epstein–Barr virus; HIES; Hyper-IgE; Hyper-IgE syndrome; LDS; Loeys–Dietz syndrome; MFS; Marfan syndrome; T(reg); TAAD; TGF-beta; TGFBR; TGFβ; Transforming growth factor beta receptor; regulatory T cells; thoracic aortic aneurysm and dissections; transforming growth factor beta