Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen
Zusammenfassung Hintergrund Eine dysregulierte Immunantwort, z. B. in der Form eines Zytokinsturmes, einer Störung des Immunglobulinklassenwechsels, eines sog. antikörpervermitteltem Enhancements oder einer aberranten Antigenpräsentation wurde bereits in schweren Krankheitsverläufen von COVID-19 bes...
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Published in | Der Pathologe Vol. 42; no. 2; pp. 188 - 196 |
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Main Authors | , , , |
Format | Journal Article |
Language | German |
Published |
Heidelberg
Springer Medizin
01.03.2021
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Subjects | |
Online Access | Get full text |
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Abstract | Zusammenfassung
Hintergrund
Eine dysregulierte Immunantwort, z. B. in der Form eines Zytokinsturmes, einer Störung des Immunglobulinklassenwechsels, eines sog. antikörpervermitteltem Enhancements oder einer aberranten Antigenpräsentation wurde bereits in schweren Krankheitsverläufen von COVID-19 beschrieben.
Ziel der Arbeit
Zur Charakterisierung der COVID-19-Immunantwort wurde die Histomorphologie der Lymphknoten des pulmonalen Abflussgebietes untersucht.
Material und Methoden
Regionale Lymphknoten des pulmonalen Abflussgebiets wurden bei COVID-19-Autopsien asserviert (
n
= 20). Deren Histomorphologie, SARS-CoV-2-qRT-PCR sowie Genexpressionsanalysen von gängigen Genen der Immunantwort wurden berücksichtigt.
Ergebnisse
Histologisch zeigten sich ein mäßig- bis schwergradiges Ödem mit Kapillarostase, eine erhöhte Anzahl von extrafollikulären Plasmablasten, milde bis mäßige Plasmazytose, vermehrte CD8
+
-T-Zellen und CD11c/CD68
+
-Histiozyten mit Hämophagozytoseaktivität. Von 20 Fällen wiesen 18 hypoplastische oder fehlende Keimzentren sowie eine Verminderung der follikulären dendritischen Zellen und follikulären T‑Helferzellen auf. In 14 von 20 Fällen war der qRT-PCR-Nachweis von SARS-CoV‑2 positiv, jedoch zeigte sich nur bei einem einzigen Fall eine immunhistochemische Positivität für SARS-CoV-2-
N
-Antigene in Sinushistiozyten. In Genexpressionsanalysen war eine erhöhte Expression von
STAT1, CD163, Granzym B, CD8A, MZB1
und
PAK1
, neben
CXCL9
zu beobachten.
Diskussion
Die Befunde in den Lymphknoten deuten auf eine dysregulierte Immunantwort bei schweren COVID-19-Krankheitsverläufen hin. Insbesondere impliziert das Ausbleiben der Keimzentrumsreaktion und die vermehrte Präsenz von Plasmablasten eine nur transiente B‑Zellreaktion, welche die Entwicklung einer Langzeitimmunität infrage stellt. |
---|---|
AbstractList | Zusammenfassung
Hintergrund
Eine dysregulierte Immunantwort, z. B. in der Form eines Zytokinsturmes, einer Störung des Immunglobulinklassenwechsels, eines sog. antikörpervermitteltem Enhancements oder einer aberranten Antigenpräsentation wurde bereits in schweren Krankheitsverläufen von COVID-19 beschrieben.
Ziel der Arbeit
Zur Charakterisierung der COVID-19-Immunantwort wurde die Histomorphologie der Lymphknoten des pulmonalen Abflussgebietes untersucht.
Material und Methoden
Regionale Lymphknoten des pulmonalen Abflussgebiets wurden bei COVID-19-Autopsien asserviert (
n
= 20). Deren Histomorphologie, SARS-CoV-2-qRT-PCR sowie Genexpressionsanalysen von gängigen Genen der Immunantwort wurden berücksichtigt.
Ergebnisse
Histologisch zeigten sich ein mäßig- bis schwergradiges Ödem mit Kapillarostase, eine erhöhte Anzahl von extrafollikulären Plasmablasten, milde bis mäßige Plasmazytose, vermehrte CD8
+
-T-Zellen und CD11c/CD68
+
-Histiozyten mit Hämophagozytoseaktivität. Von 20 Fällen wiesen 18 hypoplastische oder fehlende Keimzentren sowie eine Verminderung der follikulären dendritischen Zellen und follikulären T‑Helferzellen auf. In 14 von 20 Fällen war der qRT-PCR-Nachweis von SARS-CoV‑2 positiv, jedoch zeigte sich nur bei einem einzigen Fall eine immunhistochemische Positivität für SARS-CoV-2-
N
-Antigene in Sinushistiozyten. In Genexpressionsanalysen war eine erhöhte Expression von
STAT1, CD163, Granzym B, CD8A, MZB1
und
PAK1
, neben
CXCL9
zu beobachten.
Diskussion
Die Befunde in den Lymphknoten deuten auf eine dysregulierte Immunantwort bei schweren COVID-19-Krankheitsverläufen hin. Insbesondere impliziert das Ausbleiben der Keimzentrumsreaktion und die vermehrte Präsenz von Plasmablasten eine nur transiente B‑Zellreaktion, welche die Entwicklung einer Langzeitimmunität infrage stellt. Zusammenfassung Hintergrund Eine dysregulierte Immunantwort, z. B. in der Form eines Zytokinsturmes, einer Störung des Immunglobulinklassenwechsels, eines sog. antikörpervermitteltem Enhancements oder einer aberranten Antigenpräsentation wurde bereits in schweren Krankheitsverläufen von COVID-19 beschrieben. Ziel der Arbeit Zur Charakterisierung der COVID-19-Immunantwort wurde die Histomorphologie der Lymphknoten des pulmonalen Abflussgebietes untersucht. Material und Methoden Regionale Lymphknoten des pulmonalen Abflussgebiets wurden bei COVID-19-Autopsien asserviert ( n = 20). Deren Histomorphologie, SARS-CoV-2-qRT-PCR sowie Genexpressionsanalysen von gängigen Genen der Immunantwort wurden berücksichtigt. Ergebnisse Histologisch zeigten sich ein mäßig- bis schwergradiges Ödem mit Kapillarostase, eine erhöhte Anzahl von extrafollikulären Plasmablasten, milde bis mäßige Plasmazytose, vermehrte CD8 + -T-Zellen und CD11c/CD68 + -Histiozyten mit Hämophagozytoseaktivität. Von 20 Fällen wiesen 18 hypoplastische oder fehlende Keimzentren sowie eine Verminderung der follikulären dendritischen Zellen und follikulären T‑Helferzellen auf. In 14 von 20 Fällen war der qRT-PCR-Nachweis von SARS-CoV‑2 positiv, jedoch zeigte sich nur bei einem einzigen Fall eine immunhistochemische Positivität für SARS-CoV-2- N -Antigene in Sinushistiozyten. In Genexpressionsanalysen war eine erhöhte Expression von STAT1, CD163, Granzym B, CD8A, MZB1 und PAK1 , neben CXCL9 zu beobachten. Diskussion Die Befunde in den Lymphknoten deuten auf eine dysregulierte Immunantwort bei schweren COVID-19-Krankheitsverläufen hin. Insbesondere impliziert das Ausbleiben der Keimzentrumsreaktion und die vermehrte Präsenz von Plasmablasten eine nur transiente B‑Zellreaktion, welche die Entwicklung einer Langzeitimmunität infrage stellt. Abstract Background A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation. Objectives To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed. Materials and methods Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 ( n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed. Results Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8 + T‑cells, and CD11c/CD68 + histiocytosis with hemophagocytic activity. Out of 20 cases, 18 presented with hypoplastic or missing germinal centers with a decrease of follicular dendritic cells and follicular T‑helper cells. A positive viral load was detected by qRT-PCR in 14 of 20 cases, yet immunohistochemistry for SARS-CoV-2 N -antigen revealed positivity in sinus histiocytes of only one case. Gene expression analysis revealed an increased expression of STAT1, CD163, granzyme B, CD8A, MZB1, and PAK1, as well as CXCL9 . Conclusions Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions. |
Author | Matter, Matthias S. Stalder, Anna K. Tzankov, Alexandar Haslbauer, Jasmin D. |
Author_xml | – sequence: 1 givenname: Jasmin D. surname: Haslbauer fullname: Haslbauer, Jasmin D. organization: Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, Universität Basel – sequence: 2 givenname: Matthias S. surname: Matter fullname: Matter, Matthias S. organization: Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, Universität Basel – sequence: 3 givenname: Anna K. surname: Stalder fullname: Stalder, Anna K. organization: Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, Universität Basel – sequence: 4 givenname: Alexandar surname: Tzankov fullname: Tzankov, Alexandar email: alexandar.tzankov@usb.ch organization: Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, Universität Basel, Institut für Medizinische Genetik und Pathologie |
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Keywords | Zytokin-Freisetzungssyndrom CD8-positive T‑lymphocytes Immunohistochemistry Cytokine release syndrome Germinal center Keimzentrum Immunohistochemie SARS-CoV‑2 CD8-positive T‑Lymphozyten |
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Eine dysregulierte Immunantwort, z. B. in der Form eines Zytokinsturmes, einer Störung des Immunglobulinklassenwechsels, eines sog.... |
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Title | Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen |
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