Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Novel STAT3 Mutation Causing Hyper-IgE Syndrome: Studies of the Clinical Course and Immunopathology
Karolinska university hospital, Sweden.
Karolinska Institutet, Sweden.
Karolinska university hospital, Sweden.
Karolinska Institutet, Sweden.
Show others and affiliations
2014 (English)In: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 34, no 4, 469-477 p.Article in journal (Refereed) Published
Abstract [en]

Purpose Reporting a clinical case with a novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene resulting in autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). Here we also had the opportunity to perform in-depth immunologic investigations to further understand the immunopathology of this primary immunodeficiency. Methods The patient, a baby boy, was clinically assessed according to the scoring system developed by Grimbacher et al. and STAT3 was investigated by DNA sequencing. Immunologic work-up consisted of lymphocyte phenotyping and proliferation assays, measurement of soluble mediators and routine investigations. Results According to the Grimbacher score the patient was likely to have AD-HIES and a novel heterozygous STAT3 mutation (c.1110-3C>A), causing a splice error, was identified. Lymphocyte phenotyping revealed decreased numbers of interleukin (IL)-17 producing T-helper lymphocytes and aberrant B-lymphocyte subsets. Proliferative in vitro lymphocyte responses against C. albicans, staphylococcal enterotoxins and pokeweed mitogen were supernormal at presentation, whereas only the elevated response to pokeweed mitogen persisted. The soluble mediators IL-5, -10, -12, -13, -15 and granulocyte colony stimulatory factor were elevated in serum. Conclusion A novel heterozygous STAT3 mutation causing defective splicing of exon 12 was identified. Lymphocyte phenotyping revealed deranged subpopulations. Despite the clinical picture with severe C. albicans and staphylococcal infections, the patient’s lymphocytes mounted responses to these pathogens. The hypereosinophilia and high immunoglobulin E levels might partly be explained by elevated IL-5 and -13 as a result of lack of negative feedback from defective STAT3 signaling.

Place, publisher, year, edition, pages
2014. Vol. 34, no 4, 469-477 p.
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-205246DOI: 10.1007/s10875-014-0011-xOAI: oai:DiVA.org:kth-205246DiVA: diva2:1088071
Note

QC 20170419

Available from: 2017-04-11 Created: 2017-04-11 Last updated: 2017-04-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Thunberg, Sarah
In the same journal
Journal of Clinical Immunology
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf