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- Engblom, Camilla, et al.
(författare)
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Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 382:6675, s. 8486-
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Tidskriftsartikel (refereegranskat)abstract
- The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.
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| 2. |
- Nordström, Axel, et al.
(författare)
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Distinct eicosanoid patterns in severe recalcitrant nasal polyposis
- 2023
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Ingår i: International Forum of Allergy & Rhinology. - 2042-6984. ; 13:11, s. 2043-2054
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent NPs is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence and explored potential endotypes based on pre-surgical eicosanoid levels.METHODS: Levels of leukotriene (LT) E4 , LTB4 , prostaglandin (PG) D2 , PGE2 and 15(S) hydroxyeicosatetraenoic acid (15(S)-HETE) were measured in nasal secretions with specific immunoassays at pre-surgery (n = 38) and six- and 12-months post-surgery (n = 35) where NP recurrence was identified endoscopically. Pre- and post-surgical levels were compared between patients with and without NP recurrence. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters.RESULTS: Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD2 and LTE4 . From pre-surgery to 12-months after, NP recurrence was associated with significant decrease of 15(S)-HETE and PGD2 relative to non-recurrence whereas levels of LTE4 decreased at six-months but increased again at 12-months. Clustering revealed three potential endotypes. Cluster 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2 , lower levels of PGE2 and LTB4 , and more cases of recurrent NPs and previous NP surgeries.CONCLUSION: Elevated nasal LTE4 , 12-month post-surgery, in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies. This article is protected by copyright. All rights reserved.
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