Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity
We present the case of a 19-year-old female with a mild form of Autosomal Dominant Hyper IgE syndrome (HIES) associated with a loss-of-function mutation in STAT3. Within the first years of life she developed multiple, Staphylococcus aureus associated abscesses in the neck and face requiring frequent...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Case Reports in Immunology |
| Online Access: | http://dx.doi.org/10.1155/2019/1869524 |
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| author | Sameer Bahal Maha E. Houssen Ania Manson Lorena Lorenzo Mark A. Russell Noel G. Morgan Fariba Tahami Sofia Grigoriadou |
| author_facet | Sameer Bahal Maha E. Houssen Ania Manson Lorena Lorenzo Mark A. Russell Noel G. Morgan Fariba Tahami Sofia Grigoriadou |
| author_sort | Sameer Bahal |
| collection | DOAJ |
| description | We present the case of a 19-year-old female with a mild form of Autosomal Dominant Hyper IgE syndrome (HIES) associated with a loss-of-function mutation in STAT3. Within the first years of life she developed multiple, Staphylococcus aureus associated abscesses in the neck and face requiring frequent incision and drainage. Respiratory tract infections were not a feature of the clinical phenotype and a high resolution thoracic CT scan was unremarkable. Retained dentition was noted but fungal nail disease and recurrent thrush were absent. The total IgE was 970 IU/L, Lymphocyte counts and immunoglobulin levels were normal (IgG borderline 18.5 gr/L). There was suboptimal response to test immunisation with Pneumovax II vaccine. Th17 cell phenotyping revealed low levels of IL-17 expressing cells (0.3% of total CD4 T Cells numbers). Genetic analysis identified a missense mutation, N567D, in a conserved region of the linker domain of STAT3. Functional studies in HEK293 cells reveal that this mutation potently inhibits STAT3 activity when compared to the wildtype protein. This is consistent with other reported mutations in STAT3 associated with HIES. However, surprisingly, the magnitude of inhibition was similar to another STAT3 mutation (V637M) which causes a much more severe form of the disease. |
| format | Article |
| id | doaj-art-77605fa125ed429ea763a9b233866a2f |
| institution | Kabale University |
| issn | 2090-6609 2090-6617 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Immunology |
| spelling | doaj-art-77605fa125ed429ea763a9b233866a2f2025-02-03T01:03:12ZengWileyCase Reports in Immunology2090-66092090-66172019-01-01201910.1155/2019/18695241869524Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional ActivitySameer Bahal0Maha E. Houssen1Ania Manson2Lorena Lorenzo3Mark A. Russell4Noel G. Morgan5Fariba Tahami6Sofia Grigoriadou7Department of Immunology, Royal London Hospital, Barts Health NHS Trust, London, UKUniversity of Exeter Medical School, UKDepartment of Immunology, Addenbrooke’s Hospital, Cambridge, UKDepartment of Immunology, Royal London Hospital, Barts Health NHS Trust, London, UKUniversity of Exeter Medical School, UKUniversity of Exeter Medical School, UKDepartment of Immunology, Great Ormond Street Hospital, London, UKDepartment of Immunology, Royal London Hospital, Barts Health NHS Trust, London, UKWe present the case of a 19-year-old female with a mild form of Autosomal Dominant Hyper IgE syndrome (HIES) associated with a loss-of-function mutation in STAT3. Within the first years of life she developed multiple, Staphylococcus aureus associated abscesses in the neck and face requiring frequent incision and drainage. Respiratory tract infections were not a feature of the clinical phenotype and a high resolution thoracic CT scan was unremarkable. Retained dentition was noted but fungal nail disease and recurrent thrush were absent. The total IgE was 970 IU/L, Lymphocyte counts and immunoglobulin levels were normal (IgG borderline 18.5 gr/L). There was suboptimal response to test immunisation with Pneumovax II vaccine. Th17 cell phenotyping revealed low levels of IL-17 expressing cells (0.3% of total CD4 T Cells numbers). Genetic analysis identified a missense mutation, N567D, in a conserved region of the linker domain of STAT3. Functional studies in HEK293 cells reveal that this mutation potently inhibits STAT3 activity when compared to the wildtype protein. This is consistent with other reported mutations in STAT3 associated with HIES. However, surprisingly, the magnitude of inhibition was similar to another STAT3 mutation (V637M) which causes a much more severe form of the disease.http://dx.doi.org/10.1155/2019/1869524 |
| spellingShingle | Sameer Bahal Maha E. Houssen Ania Manson Lorena Lorenzo Mark A. Russell Noel G. Morgan Fariba Tahami Sofia Grigoriadou Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity Case Reports in Immunology |
| title | Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity |
| title_full | Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity |
| title_fullStr | Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity |
| title_full_unstemmed | Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity |
| title_short | Evidence that a STAT3 Mutation Causing Hyper IgE Syndrome Leads to Repression of Transcriptional Activity |
| title_sort | evidence that a stat3 mutation causing hyper ige syndrome leads to repression of transcriptional activity |
| url | http://dx.doi.org/10.1155/2019/1869524 |
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