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C-reaktives Protein und andere immunologische Biomarker

Sinn und Unsinn in der Infektionsdiagnostik

C-reactive protein and other immunological biomarkers

Sense and nonsense in the diagnosis of infectious diseases

  • Leitthema
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Zusammenfassung

Die Untersuchung von Laborbiomarkern wird im klinischen Alltag des Kinderarztes extrem häufig eingesetzt. Auf Basis einer breiten Literatursuche wird die Evidenz zum Einsatz von Biomarkern für das Management von Infektionen, insbesondere von schweren bakteriellen Infektionen (SBI), analysiert. Vor dem Hintergrund der physiologischen Entzündungsreaktion wird die Rolle klassischer Entzündungsmarker wie C‑reaktives Protein (CRP) und Prokalzitonin (PCT), von Zytokinen und hämatologischen Markern (z. B. Blutbild) sowie neuer Laborverfahren (z. B. Transkriptom- und Proteomanalysen) bei der Infektionsdiagnostik in übersichtlicher Form dargestellt. Es wird diskutiert, ob ein generelles Screening mit Labormarkern in der Notfallsituation sinnvoll ist, ob Laborbiomarker zwischen bakteriellen und nichtbakteriellen Infektionen unterscheiden können und wie gut sie sich für die Früherkennung und die Verlaufsbeurteilung von SBI eignen. Statistisch gesehen sind die Konzentrationen klassischer Biomarker wie CRP und PCT bei bakteriellen Infektionen zwar höher als bei viralen Infektionen, im Einzelfall hilft der einzelne CRP- oder PCT-Wert aber nicht bei der Unterscheidung. Die Kombination der Befunde aus Anamnese/körperlicher Untersuchung (klinisch-biometrische Biomarker) und Laborbiomarkern stellt den erfolgreichsten Ansatz zur Früherkennung von SBI dar. Mit Ausnahme der Neonatologie fehlen Daten aus gut durchgeführten klinischen Studien, um den Nutzen der Laborbiomarker für die Verlaufsbeurteilung und die Steuerung der Therapie zu belegen. Ein kritischerer Einsatz von Laborbiomarkern in Praxis und Klinik als bisher ist angezeigt, um unnötige Eingriffe und Therapien bei Kindern zu vermeiden.

Abstract

Laboratory biomarkers are very frequently employed for in- and outpatient emergency work-up of children with infectious diseases and evaluation of severe bacterial infection (SBI). Based on a literature review, the evidence for the use of biomarkers in the management of infections was analyzed. The physiological inflammatory response and the role of classical inflammation markers, such as C‑reactive protein (CRP), procalcitonin (PCT), hematological (blood count) and new laboratory biomarkers (e. g. transcriptome and proteome analyses) are described. It is discussed whether a general screening with laboratory markers makes sense in emergency situations, whether laboratory biomarkers can differentiate between bacterial and non-bacterial infections and how well they are qualified for the early detection and evaluation of the course of SBI. On a purely statistical basis, the values of classical biomarkers, such as CRP and PCT are higher in bacterial than in viral infections; however, in the individual case a single, isolated CRP or PCT value does not reliably help to differentiate. The combined use of findings from taking a patient history/physical examination (clinical biometric biomarkers) and laboratory biomarkers is the most successful approach to improve early detection of SBI. Except in neonatology reliable data regarding the benefit of laboratory biomarkers for assessment of progress and steering therapy are missing. A more critical use of laboratory biomarkers in Pediatrics would be desirable in order to prevent unnecessary medical interventions and therapy in children.

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Abbreviations

APP:

Akute-Phase-Protein

APR:

Akute-Phase-Reaktion

BSG:

Blutkörperchensenkungsgeschwindigkeit („erythrocyte sedimentation rate“, ESR)

CD:

„cluster of differentiation“

CRP:

C-reaktives Protein

CSF:

„cerebrospinal fluid“ (Liquor cerebrospinalis)

CXCL8:

CXC-Motiv-Chemokinligand 8 (Interleukin-8)

D/PAMP:

„damage/pathogen-associated molecular pattern“

FcRγ:

Fc-Rezeptor‑γ

GBS:

Gruppe-B-Streptokokken

G-CSF:

Granulozyten-koloniestimulierender Faktor

GM-CSF:

Granulozyten-Monozyten-koloniestimulierender Faktor

IBI:

invasive bakterielle Infektion (Bakteriämie, Sepsis, Meningitis)

IFN:

Interferon

IL:

Interleukin

IP-10:

„interferon-gamma induced protein 10“

LPS:

Lipopolysaccharid

NPV:

„negative predictive value“ (negativer Vorhersagewert)

PC:

Phosphocholine

pCAP:

„pediatric community-acquired pneumonia“ (außerhalb des Krankenhauses erworbene Pneumonie bei Kdr.)

PCT:

Prokalzitonin

PPV:

„positive predictive value“ (positiver Vorhersagewert)

PRR:

„pattern recognition receptor“ (Mustererkennungsrezeptor)

RSV:

Respiratory Syncytial Virus

SBI:

schwere bakterielle Infektion (Sepsis, Meningitis, Appendizitis, Pneumonie, Osteomyelitis, Zellulitis, bakterielle Gastroenteritis, komplizierte Harnwegsinfektionen)

SSW:

Schwangerschaftswoche

TNF-α:

Tumor-Nekrose-Faktor-α

TRAIL:

„tumor necrosis factor apoptosis inducing ligand“

WBC:

„white blood cells“ (Leukozyten)

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Danksagung

Für die kritische und konstruktive Durchsicht des Manuskripts danke ich folgenden Kollegen: Dres. Marion Riffelmann (Krefeld), Peter Heister, Gregor Dückers (beide Krefeld). Die Herstellung des Manuskripts wäre ohne die intensive sekretarielle Bearbeitung von Andrea Groth nicht möglich gewesen.

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  1. Zentrum für Kinder- und Jugendmedizin, HELIOS Klinikum Krefeld, Akademisches Lehrkrankenhaus, RWTH Aachen, Lutherplatz 40, 47805, Krefeld, Deutschland

    T. Niehues

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L. Weber, Köln

F. Zepp, Mainz

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Niehues, T. C-reaktives Protein und andere immunologische Biomarker. Monatsschr Kinderheilkd 165, 560–571 (2017). https://doi.org/10.1007/s00112-017-0314-0

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