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Fibrotischer Lungenparenchymumbau nach Lungen- und Stammzelltransplantation

Fibrotic remodeling of the lung following lung and stem-cell transplantation

  • Schwerpunkt: Nicht-neoplastische Lungenerkrankungen
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A Publisher's Erratum to this article was published on 22 January 2021

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Zusammenfassung

Wenngleich die Sterblichkeit von Patienten nach Lungen- oder Stammzelltransplantation deutlich verbessert werden konnte, weisen beide Therapieverfahren weiterhin eine hohe 5‑Jahres-Mortalität auf. Dies ist Folge insbesondere von Lungenerkrankungen als Ausdruck einer chronischen Alloimmunreaktion. Morphologisch stehen fibrosierende Parenchymveränderungen mit Umbau der Atemwege im Sinne einer Bronchiolitis obliterans oder Umbau des Alveolarparenchyms im Sinne einer alveolären Fibroelastose im Vordergrund. Molekulare Studien dokumentieren viele Parallelen, jedoch auch distinkte Unterschiede zwischen diesen klinisch und morphologisch deutlich divergierenden Entitäten. Es zeigt sich erneut, dass histomorphologisch abgrenzbare Muster des fibrotischen Parenchymumbaus für sich genommen unspezifisch, in Zusammenschau mit den klinisch-radiologischen Befunden jedoch bestimmten Entitäten mit zum Teil deutlich unterschiedlichen Prognosen und Therapien zuordenbar sind.

Fortschritte des molekularen Verständnisses dieser Läsionen sind Grundlage für eine frühe Vorhersage und exaktere Diagnose irreversibler fibrotischer Veränderungen der Lunge und für die mögliche Entwicklung bisher fehlender Therapieoptionen

Abstract

Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Although the overall survival following transplantation has generally improved over recent decades, long-time survival of lung and stem-cell transplant recipients is still alarmingly low with an average 5‑year survival rate of only 50–60%. Chronic allo-immunoreactions in general and pulmonary allo-immunoreactions with subsequent fibrosis in particular are major reasons for this poor outcome. Comparable patterns of fibrotic lung remodeling are observed following both lung and hematopoietic stem-cell transplantation. Besides the meanwhile well-established obliterative and functionally obstructive remodeling of the small airways – obliterative bronchiolitis – a specific restrictive subform of fibrosis, namely alveolar fibroelastosis, has been identified. Despite their crucial impact on patient outcome, both entities can be very challenging to detect by conventional histopathological analysis. Their underlying mechanisms are considered overreaching aberrant repair attempts to acute lung injuries with overactivation of (myo-) fibroblasts and excessive and irreversible deposition of extracellular matrix. Of note, the underlying molecular mechanisms are widely divergent between these two morphological entities and are independent of the underlying clinical setting.

Further comprehensive investigations of these fibrotic alterations are key to the development of much-needed predictive diagnostics and curative concepts, considering the high mortality of pulmonary fibrosis following transplantation.

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Change history

  • 22 January 2021

    Ein Erratum zu dieser Publikation wurde veröffentlicht: <ExternalRef><RefSource>https://doi.org/10.1007/s00292-020-00907-4</RefSource><RefTarget Address="10.1007/s00292-020-00907-4" TargetType="DOI"/></ExternalRef>

Abbreviations

AFE:

Alveoläre Fibroelastose

AFOP:

Akute fibrinöse und organisierende Pneumonie

ARDS:

„Acute respiratory distress syndrome“

ATP:

Adenosintriphosphat

BMP1, 2, 4:

„Bone morphogenic protein 1, 2, 4“

BO:

Bronchiolitis obliterans

BOS:

Bronchiolitis-obliterans-Syndrom

CCL5:

„CC-chemokine ligand 5“

CF:

„Cystic fibrosis“

CLAD:

„Chronic lung allograft dysfunction“

COPD:

„Chronic obstructive pulmonary disease“

CXCL-12:

CXC-Motiv-Chemokin 12

CXCR 2, 4:

CXC-Motiv-Chemokinrezeptor 2, 4

DAD:

„Diffuse alveolar damage“

DIP:

„Desquamative interstitial pneumonia“

EMT:

„Epithelial mesenchymale transition“

EZM:

Extrazelluläre Matrix

GvHD:

„Graft versus host disease“

IIP:

„Idiopathic interstitial pneumonia“

IL‑6:

Interleukin 6

IL‑8:

Interleukin 8

IL-17:

Interleukin 17

IPF:

„Idiopathic pulmonary fibrosis“

IPPFE:

„Idiopathic pleuroparenchymal fibroelastosis“

IFN‑γ:

Interferon-gamma

LuTx:

Lungentransplantation

MHC:

„Major histocompatibility complex“

MMP:

„Matrix metalloproteinases“

NK-Zellen:

Natürliche Killerzellen

NSIP:

„Nonspecific interstitial pneumonia“

oCLAD:

„Obstructive chronic lung allograft dysfunction“

OP:

„Organizing pneumonia“

PLAT:

„Tissue-type plasminogen activator“

PLAUR:

„Urokinase plasminogen activator surface receptor“

PLOD:

„Procollagen-lysine“

PPFE:

„Pleuroparenchymal fibroelastosis“

rCLAD/RAS:

„Restrictive allograft dysfunction syndrome“

SMAD1:

„Mothers against decapentaplegic homolog 1“

TGF β:

„Transforming growth factor β“

THBS1:

Thrombospondin‑1

Tregs:

„Regulatory T‑lymphocytes“

UIP:

„Usual interstitial pneumonia“

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Förderung

The grants of the European Research Council (ERC); European Consolidator Grant, XHale an Danny Jonigk (ref. no. 771883).

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Authors and Affiliations

  1. Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, OE 5110, 30625, Hannover, Deutschland

    Christopher Werlein, Thia Leandra Hoffmann, Florian Laenger &  Danny Jonigk FRCPath

  2. Institut für Pathologie und Molekularpathologie, Helios Universitätsklinikum Wuppertal, Universität Witten-Herdecke, Wuppertal, Deutschland

    Max Ackermann

  3. Institut für Funktionelle und Klinische Anatomie, Universitätsmedizin, Johannes Gutenberg-Universität Mainz, Mainz, Deutschland

    Max Ackermann

  4. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Standort Hannover, Deutsches Zentrum für Lungenforschung (DZL), Hannover, Deutschland

    Florian Laenger &  Danny Jonigk FRCPath

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  1. Christopher Werlein
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Correspondence to Danny Jonigk FRCPath.

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Interessenkonflikt

C. Werlein, M. Ackermann, T.L. Hoffmann, F. Laenger und D. Jonigk geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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S. Perner, Lübeck

F. Stellmacher, Borstel

Die ursprüngliche Online-Version dieses Artikels wurde überarbeitet: Die Angaben der Schwerpunktherausgeber wurden korrigiert.

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Werlein, C., Ackermann, M., Hoffmann, T.L. et al. Fibrotischer Lungenparenchymumbau nach Lungen- und Stammzelltransplantation. Pathologe 42, 17–24 (2021). https://doi.org/10.1007/s00292-020-00898-2

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