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Measures of Classical and Alternative Complement Function in Serum as Markers in Critical Care

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Biomarkers in Trauma, Injury and Critical Care

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Abstract

The human complement system is a crucial component of the host response to pathogen invaders, cellular stress, and injury – all of which are common causes and manifestations of critical illness. The complement cascade can be activated by alternative, classical, and lectin pathways that function as immune recognition pathways. Yet, the capacity of the complement system to respond to infection and injury depends not only on the ability to activate but also on effective regulation to prevent complement factor exhaustion, limit inflammation, and preserve complement function to respond to threats. Therefore, measurements of complement pathway function and levels of specific complement proteins may serve as useful biomarkers during critical illness. Complement activity or function is widely variable during critical illness caused by sepsis and other infections, acute respiratory failure including pneumonia, and during the massive injury of trauma. Preserved complement function has been associated with improved outcomes across numerous investigations. However, whether preservation of complement function is a causal mechanism or the consequence of decreased burden of pathogen or injury is unclear and worthy of future research. Herein, we present key biology of the complement system, review assays of complement function, and describe key findings of the existing literature evaluating complement function during critical illness. We further present potential topics for future research on the complement system during critical illness.

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Abbreviations

AH50:

Hemolytic assay utilized to evaluate alternative complement pathway function

ARDS:

Acute respiratory distress syndrome

CH50:

Hemolytic assay utilized to evaluate classical complement pathway function

COVID-19:

Coronavirus disease 2019, the human disease caused by the SARS-CoV-2 virus

EDTA:

Ethylenediaminetetraacetic acid, a protease inhibitor that chelates calcium, magnesium, and other ions

EGTA:

Ethylene-bis(oxyethylenenitrilo)tetraacetic acid, a chelating agent related to EDTA but with lower affinity for magnesium

ELISA:

Enzyme-linked immunosorbent assay

ICU:

Intensive care unit

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

LPS:

Lipopolysaccharide

MAC:

Membrane attack complex

MASP:

MBL-associated serine protease

MBL:

Mannose-binding lectin

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

sC5b-C9:

Soluble form of protein complex known as membrane attack complex that is terminal protein complex of complement action

SNP:

Single nucleotide polymorphism

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Authors and Affiliations

  1. Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    William Bain, Shekina Gonzalez-Ferrer, S. Mehdi Nouraie & Janet S. Lee

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  1. William Bain
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  2. Shekina Gonzalez-Ferrer
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  3. S. Mehdi Nouraie
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  4. Janet S. Lee
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Correspondence to Janet S. Lee .

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Editors and Affiliations

  1. Department of Medicine, King Abdulaziz Med City, Riyadh, Saudi Arabia

    Rajkumar Rajendram

  2. Franklin-Wilkins Bldg, Rm 4.101, 4th Fl, Kings Coll London, Sch Biomed Health Sci, London, UK

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, UK

    Vinood B. Patel

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Bain, W., Gonzalez-Ferrer, S., Nouraie, S.M., Lee, J.S. (2022). Measures of Classical and Alternative Complement Function in Serum as Markers in Critical Care. In: Rajendram, R., Preedy, V.R., Patel, V.B. (eds) Biomarkers in Trauma, Injury and Critical Care. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-87302-8_13-1

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