Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders

Clin Immunol. 2014 Jan;150(1):43-50. doi: 10.1016/j.clim.2013.11.008. Epub 2013 Nov 19.

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.

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.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Connective Tissue Diseases / blood
  • Connective Tissue Diseases / genetics
  • Connective Tissue Diseases / immunology
  • Cytokines / immunology
  • Eczema / blood*
  • Eczema / genetics
  • Eczema / immunology
  • Female
  • Humans
  • Immunoglobulin E / blood*
  • Job Syndrome / blood
  • Job Syndrome / genetics
  • Job Syndrome / immunology
  • Loeys-Dietz Syndrome / blood*
  • Loeys-Dietz Syndrome / genetics
  • Loeys-Dietz Syndrome / immunology
  • Middle Aged
  • Mutation, Missense
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / immunology
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / immunology
  • STAT3 Transcription Factor / blood
  • STAT3 Transcription Factor / deficiency
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • Transforming Growth Factor beta / immunology

Substances

  • Cytokines
  • Receptors, Transforming Growth Factor beta
  • STAT3 Transcription Factor
  • Transforming Growth Factor beta
  • Immunoglobulin E
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human

Supplementary concepts

  • Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant