Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved..
OBJECTIVES: Lymphopenia at hospital admission occurs in over one-third of patients with community-acquired pneumonia (CAP), yet its clinical relevance and pathophysiological implications remain underexplored. We evaluated outcomes and immune features of patients with lymphopenic CAP (L-CAP), a previously described immunophenotype characterized by admission lymphocyte count <0.724 × 109 cells/L.
METHODS: Observational study in 149 patients admitted to a general ward for CAP. We measured 34 plasma biomarkers reflective of inflammation, endothelial cell responses, coagulation, and immune checkpoints. We characterized lymphocyte phenotypes in 29 patients using spectral flow cytometry.
RESULTS: L-CAP occurred in 45 patients (30.2%) and was associated with prolonged time-to-clinical-stability (median 5 versus 3 days), also when we accounted for competing events for reaching clinical stability and adjusted for baseline covariates (subdistribution hazard ratio 0.63; 95% confidence interval 0.45-0.88). L-CAP patients demonstrated a proportional depletion of CD4 T follicular helper cells, CD4 T effector memory cells, naïve CD8 T cells and IgG+ B cells. Plasma biomarker analyses indicated increased activation of the cytokine network and the vascular endothelium in L-CAP.
CONCLUSIONS: L-CAP patients have a protracted clinical recovery course and a more broadly dysregulated host response. These findings highlight the prognostic and pathophysiological relevance of admission lymphopenia in patients with CAP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
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| Enthalten in: |
The Journal of infection - 88(2024), 4 vom: 15. Apr., Seite 106131 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Doeleman, Susanne E [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jinf.2024.106131 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369210344 |
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| 100 | 1 | |a Doeleman, Susanne E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia |
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| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a OBJECTIVES: Lymphopenia at hospital admission occurs in over one-third of patients with community-acquired pneumonia (CAP), yet its clinical relevance and pathophysiological implications remain underexplored. We evaluated outcomes and immune features of patients with lymphopenic CAP (L-CAP), a previously described immunophenotype characterized by admission lymphocyte count <0.724 × 109 cells/L | ||
| 520 | |a METHODS: Observational study in 149 patients admitted to a general ward for CAP. We measured 34 plasma biomarkers reflective of inflammation, endothelial cell responses, coagulation, and immune checkpoints. We characterized lymphocyte phenotypes in 29 patients using spectral flow cytometry | ||
| 520 | |a RESULTS: L-CAP occurred in 45 patients (30.2%) and was associated with prolonged time-to-clinical-stability (median 5 versus 3 days), also when we accounted for competing events for reaching clinical stability and adjusted for baseline covariates (subdistribution hazard ratio 0.63; 95% confidence interval 0.45-0.88). L-CAP patients demonstrated a proportional depletion of CD4 T follicular helper cells, CD4 T effector memory cells, naïve CD8 T cells and IgG+ B cells. Plasma biomarker analyses indicated increased activation of the cytokine network and the vascular endothelium in L-CAP | ||
| 520 | |a CONCLUSIONS: L-CAP patients have a protracted clinical recovery course and a more broadly dysregulated host response. These findings highlight the prognostic and pathophysiological relevance of admission lymphopenia in patients with CAP | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biomarkers | |
| 650 | 4 | |a Community-acquired pneumonia | |
| 650 | 4 | |a Host response | |
| 650 | 4 | |a Immunophenotyping | |
| 650 | 4 | |a Lymphopenia | |
| 700 | 1 | |a Reijnders, Tom D Y |e verfasserin |4 aut | |
| 700 | 1 | |a Joosten, Sebastiaan C M |e verfasserin |4 aut | |
| 700 | 1 | |a Schuurman, Alex R |e verfasserin |4 aut | |
| 700 | 1 | |a van Engelen, Tjitske S R |e verfasserin |4 aut | |
| 700 | 1 | |a Verhoeff, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Léopold, Valentine |e verfasserin |4 aut | |
| 700 | 1 | |a Brands, Xanthe |e verfasserin |4 aut | |
| 700 | 1 | |a Haak, Bastiaan W |e verfasserin |4 aut | |
| 700 | 1 | |a Prins, Jan M |e verfasserin |4 aut | |
| 700 | 1 | |a Kanglie, Maadrika M N P |e verfasserin |4 aut | |
| 700 | 1 | |a van den Berk, Inge A H |e verfasserin |4 aut | |
| 700 | 1 | |a Faber, Daniël R |e verfasserin |4 aut | |
| 700 | 1 | |a Douma, Renée A |e verfasserin |4 aut | |
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| 700 | 1 | |a Saris, Anno |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia Vallejo, Juan J |e verfasserin |4 aut | |
| 700 | 1 | |a Wiersinga, W Joost |e verfasserin |4 aut | |
| 700 | 1 | |a van der Poll, Tom |e verfasserin |4 aut | |
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