TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS
Objective: The TNF receptor gene 13B (TNFSRF13B) is a member of the TNF superfamily which is crucial for B cell maturation, plasma cell differentiation, and antibody response. Impaired expression of the TNFRSF13B gene is associated with common variable immune deficiency (CVID), autoimmunity, and lym...
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Istanbul University Press
2023-10-01
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| Series: | Sabiad |
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| Online Access: | https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/E2CF0E56089245BFAA286E3C6775A853 |
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| author | Sinem Fırtına Aslı Kutlu Begüm Işıkgil Medinenur Yozlu Beyza Nur Cepeci Hülya Yılmaz Yuk Yin Ng Özden Hatırnaz Ng Ayça Kıykım Esra Özek Yücel Elif Karakoç Aydıner Safa Barış Ahmet Oğuzhan Özen Serdar Nepesov Yıldız Çamcıoğlu İsmail Reisli Muhlis Cem Ar Müge Sayitoğlu |
| author_facet | Sinem Fırtına Aslı Kutlu Begüm Işıkgil Medinenur Yozlu Beyza Nur Cepeci Hülya Yılmaz Yuk Yin Ng Özden Hatırnaz Ng Ayça Kıykım Esra Özek Yücel Elif Karakoç Aydıner Safa Barış Ahmet Oğuzhan Özen Serdar Nepesov Yıldız Çamcıoğlu İsmail Reisli Muhlis Cem Ar Müge Sayitoğlu |
| author_sort | Sinem Fırtına |
| collection | DOAJ |
| description | Objective: The TNF receptor gene 13B (TNFSRF13B) is a member of the TNF superfamily which is crucial for B cell maturation, plasma cell differentiation, and antibody response. Impaired expression of the TNFRSF13B gene is associated with common variable immune deficiency (CVID), autoimmunity, and lymphoproliferation disorders. Besides the disease-causing variants of this gene, its different isoforms are associated with strong and weak TNFRSF13B expression that leads to an unbalanced B cell response.Materials and Methods: The study detected 26 variants (three synonymous, five missenses, eleven UTR, and seven intronic variants) in the TNFRSF13B gene by screening 68 CVID patients with targeted next generation sequencing. An integrative bioinformatics approach was utilized to provide a plausible explanation for CVID associations from different perspectives and to investigate the associations from the clinical findings.Results: Fifty-eight percent (15/26) of the detected variants were altered regulatory elements, such as transcription factor binding, miRNA binding sites, splice site regions or the thermodynamic impact on protein. We observed that patients who suffered from the potential splicing variants had significantly low IgA levels (p=0.009), autoimmunity (p=0.02) and gastrointestinal findings (p=0.05). In addition, the c.*79A>G 3-UTR variant was found with the low IgA and IgE levels. Thirteen variants found to have at least tenfold increased allele frequencies as compared to global databases indicating that the TNFRSF13B variants, which have a potential regulatory effect, are more common in CVID patients.Conclusions: All findings suggested that these variants may not be the causative variant for the CVID phenotype but the unbalanced TNFRSF13B alternative splices could contribute to the pathogenesis of patients independent from the underlying genetic background of CVID. |
| format | Article |
| id | doaj-art-6a0ed623798c4989a7c5fd2e5c73035c |
| institution | OA Journals |
| issn | 2651-4060 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | Istanbul University Press |
| record_format | Article |
| series | Sabiad |
| spelling | doaj-art-6a0ed623798c4989a7c5fd2e5c73035c2025-08-20T02:27:31ZengIstanbul University PressSabiad2651-40602023-10-016321021810.26650/JARHS2023-1346155123456TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERSSinem Fırtına0https://orcid.org/0000-0002-3370-8545Aslı Kutlu1https://orcid.org/0000-0002-9169-388XBegüm Işıkgil2https://orcid.org/0000-0002-7541-4596Medinenur Yozlu3https://orcid.org/0000-0002-3580-7280Beyza Nur Cepeci4https://orcid.org/0000-0001-9417-2943Hülya Yılmaz5https://orcid.org/0000-0001-5664-5893Yuk Yin Ng6https://orcid.org/0000-0001-9755-6045Özden Hatırnaz Ng7https://orcid.org/0000-0001-7728-6527Ayça Kıykım8https://orcid.org/0000-0001-5821-3963Esra Özek Yücel9https://orcid.org/0000-0003-3712-2522Elif Karakoç Aydıner10https://orcid.org/0000-0003-4150-5200Safa Barış11https://orcid.org/0000-0002-4730-9422Ahmet Oğuzhan Özen12https://orcid.org/0000-0002-9065-1901Serdar Nepesov13https://orcid.org/0000-0002-4551-5433Yıldız Çamcıoğlu14https://orcid.org/0000-0002-4796-6828İsmail Reisli15https://orcid.org/0000-0001-8247-6405Muhlis Cem Ar16https://orcid.org/0000-0002-0332-9253Müge Sayitoğlu17https://orcid.org/0000-0002-8648-213Xİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, TurkiyeGebze Teknik Üniversitesi, Kocaeli, TurkiyeGebze Teknik Üniversitesi, Kocaeli, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Bilgi Üniversitesi, İstanbul, TürkiyeAcıbadem Mehmet Ali Aydınlar Üniversitesi, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi, İstanbul, TürkiyeMarmara Üniversitesi, İstanbul, TürkiyeMarmara Üniversitesi, İstanbul, TürkiyeMarmara Üniversitesi, İstanbul, TürkiyeMedical Park Hastanesi, İstanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, TurkiyeNecmettin Erbakan Üniversitesi, Konya, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi, İstanbul, TürkiyeObjective: The TNF receptor gene 13B (TNFSRF13B) is a member of the TNF superfamily which is crucial for B cell maturation, plasma cell differentiation, and antibody response. Impaired expression of the TNFRSF13B gene is associated with common variable immune deficiency (CVID), autoimmunity, and lymphoproliferation disorders. Besides the disease-causing variants of this gene, its different isoforms are associated with strong and weak TNFRSF13B expression that leads to an unbalanced B cell response.Materials and Methods: The study detected 26 variants (three synonymous, five missenses, eleven UTR, and seven intronic variants) in the TNFRSF13B gene by screening 68 CVID patients with targeted next generation sequencing. An integrative bioinformatics approach was utilized to provide a plausible explanation for CVID associations from different perspectives and to investigate the associations from the clinical findings.Results: Fifty-eight percent (15/26) of the detected variants were altered regulatory elements, such as transcription factor binding, miRNA binding sites, splice site regions or the thermodynamic impact on protein. We observed that patients who suffered from the potential splicing variants had significantly low IgA levels (p=0.009), autoimmunity (p=0.02) and gastrointestinal findings (p=0.05). In addition, the c.*79A>G 3-UTR variant was found with the low IgA and IgE levels. Thirteen variants found to have at least tenfold increased allele frequencies as compared to global databases indicating that the TNFRSF13B variants, which have a potential regulatory effect, are more common in CVID patients.Conclusions: All findings suggested that these variants may not be the causative variant for the CVID phenotype but the unbalanced TNFRSF13B alternative splices could contribute to the pathogenesis of patients independent from the underlying genetic background of CVID.https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/E2CF0E56089245BFAA286E3C6775A853tnfrsf13bin silico analysiscvidintegrated bioinformaticspid |
| spellingShingle | Sinem Fırtına Aslı Kutlu Begüm Işıkgil Medinenur Yozlu Beyza Nur Cepeci Hülya Yılmaz Yuk Yin Ng Özden Hatırnaz Ng Ayça Kıykım Esra Özek Yücel Elif Karakoç Aydıner Safa Barış Ahmet Oğuzhan Özen Serdar Nepesov Yıldız Çamcıoğlu İsmail Reisli Muhlis Cem Ar Müge Sayitoğlu TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS Sabiad tnfrsf13b in silico analysis cvid integrated bioinformatics pid |
| title | TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS |
| title_full | TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS |
| title_fullStr | TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS |
| title_full_unstemmed | TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS |
| title_short | TNFRSF13B VARIANTS ACT AS MODIFIERS TO CLINICAL PHENOTYPES IN COMMON VARIABLE IMMUNE DEFICIENCY DISORDERS |
| title_sort | tnfrsf13b variants act as modifiers to clinical phenotypes in common variable immune deficiency disorders |
| topic | tnfrsf13b in silico analysis cvid integrated bioinformatics pid |
| url | https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/E2CF0E56089245BFAA286E3C6775A853 |
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