Academic Journal
Somatic mutations and T-cell clonality in patients with immunodeficiency
| العنوان: | Somatic mutations and T-cell clonality in patients with immunodeficiency |
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| المؤلفون: | Savola, Paula, Martelius, Timi, Kankainen, Matti, Huuhtanen, Jani, Lundgren, Sofie, Koski, Yrjö, Samuli, Eldfors, Kelkka, Tiina, Keränen, Mikko A I, Ellonen, Pekka, Kovanen, Panu E, Kytölä, Soili, Saarela, Janna Saija, Lähdesmäki, Harri, Seppänen, Mikko R J, Mustjoki, Satu |
| المصدر: | 0390-6078. |
| سنة النشر: | 2022 |
| المجموعة: | Universitet i Oslo: Digitale utgivelser ved UiO (DUO) |
| الوصف: | Common variable immunodeficiency and other late-onset immunodeficiencies often co-manifest with autoimmunity and lymphoproliferation. The pathogenesis of most cases is elusive, as only a minor subset harbors known monogenic germline causes. The involvement of both B and T cells is however implicated. To study whether somatic mutations in CD4+ and CD8+ T cells associate with immunodeficiency, we recruited 17 patients and 21 healthy controls. Eight patients had late-onset common variable immunodeficiency and nine patients other immunodeficiency and/or severe autoimmunity. In total, autoimmunity occurred in 94% and lymphoproliferation in 65%. We performed deep sequencing of 2533 immune-associated genes from CD4+ and CD8+ cells. Deep T-cell receptor beta sequencing was used to characterize CD4+ and CD8+ T-cell receptor repertoires. The prevalence of somatic mutations was 65% in all immunodeficiency patients, 75% in common variable immunodeficiency and 48% in controls. Clonal hematopoiesis-associated variants in both CD4+ and CD8+ cells occurred in 24% of immunodeficiency patients. Results demonstrated mutations in known tumor suppressors, oncogenes, and genes that are critical for immune- and proliferative functions, such as STAT5B (two patients), C5AR1 (two patients), KRAS (one patient), and NOD2 (one patient). Additionally, as a marker of T-cell receptor repertoire perturbation, common variable immunodeficiency patients harbored increased frequencies of clones with identical complementarity determining region 3 sequences despite unique nucleotide sequences when compared to controls. In conclusion, somatic mutations in genes implicated for autoimmunity and lymphoproliferation are common in CD4+ and CD8+ cells of patients with immunodeficiency. They may contribute to immune dysregulation in a subset of immunodeficiency patients. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | NFR/187615; http://urn.nb.no/URN:NBN:no-93678; Savola, Paula Martelius, Timi Kankainen, Matti Huuhtanen, Jani Lundgren, Sofie Koski, Yrjö Samuli, Eldfors Kelkka, Tiina Keränen, Mikko A I Ellonen, Pekka Kovanen, Panu E Kytölä, Soili Saarela, Janna Saija Lähdesmäki, Harri Seppänen, Mikko R J Mustjoki, Satu . Somatic mutations and T-cell clonality in patients with immunodeficiency. Haematologica. 2021; http://hdl.handle.net/10852/91049; 1989230; info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Haematologica&rft.volume=&rft.spage=&rft.date=2021; Haematologica; 105; 12; 2757; 2768; https://doi.org/10.3324/haematol.2019.220889; URN:NBN:no-93678; Fulltext https://www.duo.uio.no/bitstream/handle/10852/91049/1/9576-Article%2BText-70966-2-10-20201117.pdf |
| DOI: | 10.3324/haematol.2019.220889 |
| الاتاحة: | http://hdl.handle.net/10852/91049 http://urn.nb.no/URN:NBN:no-93678 https://doi.org/10.3324/haematol.2019.220889 |
| Rights: | Attribution-NonCommercial 4.0 International ; https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.75A8AA92 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3324/haematol.2019.220889 |
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