STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria
BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.902652/full |
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| author | Merle Sauer Jörg Scheffel Jörg Scheffel Stefan Frischbutter Stefan Frischbutter Niklas Mahnke Niklas Mahnke Marcus Maurer Marcus Maurer Thomas Burmeister Karoline Krause Karoline Krause Martin Metz Martin Metz |
| author_facet | Merle Sauer Jörg Scheffel Jörg Scheffel Stefan Frischbutter Stefan Frischbutter Niklas Mahnke Niklas Mahnke Marcus Maurer Marcus Maurer Thomas Burmeister Karoline Krause Karoline Krause Martin Metz Martin Metz |
| author_sort | Merle Sauer |
| collection | DOAJ |
| description | BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.ObjectiveOur aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb.MethodsWe included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.ResultsNo differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients.ConclusionIn total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb. |
| first_indexed | 2024-04-12T07:10:21Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T07:10:21Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-38ff875985474b7d9f682856efcb4bec2022-12-22T03:42:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.902652902652STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticariaMerle Sauer0Jörg Scheffel1Jörg Scheffel2Stefan Frischbutter3Stefan Frischbutter4Niklas Mahnke5Niklas Mahnke6Marcus Maurer7Marcus Maurer8Thomas Burmeister9Karoline Krause10Karoline Krause11Martin Metz12Martin Metz13Institute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyDepartment of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyInstitute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, GermanyBackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.ObjectiveOur aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb.MethodsWe included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.ResultsNo differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients.ConclusionIn total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb.https://www.frontiersin.org/articles/10.3389/fimmu.2022.902652/fullautoimmune diseaseautoreactivitybasophil activation testchronic spontaneous urticariagain-of-function mutationimmunoglobulin E |
| spellingShingle | Merle Sauer Jörg Scheffel Jörg Scheffel Stefan Frischbutter Stefan Frischbutter Niklas Mahnke Niklas Mahnke Marcus Maurer Marcus Maurer Thomas Burmeister Karoline Krause Karoline Krause Martin Metz Martin Metz STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria Frontiers in Immunology autoimmune disease autoreactivity basophil activation test chronic spontaneous urticaria gain-of-function mutation immunoglobulin E |
| title | STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria |
| title_full | STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria |
| title_fullStr | STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria |
| title_full_unstemmed | STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria |
| title_short | STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria |
| title_sort | stat3 gain of function is not responsible for low total ige levels in patients with autoimmune chronic spontaneous urticaria |
| topic | autoimmune disease autoreactivity basophil activation test chronic spontaneous urticaria gain-of-function mutation immunoglobulin E |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.902652/full |
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