Evidence map›Paper›PMID 36330514›Full record

SynthesisFrontiers in immunology2022

Pitfalls in complement analysis: A systematic literature review of assessing complement activation.

Ricardo J M G E Brandwijk, Marloes A H M Michels, Mara van Rossum, Aline H de Nooijer, Per H Nilsson, Wieke C C de Bruin, Erik J M Toonen

Open access · goldAbstract readSystematic Review
In one paragraph

Synthesis in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
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  7. A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Ricardo J M G E BrandwijkR&D Department, Hycult Biotechnology b.v., Uden, Netherlands.
Marloes A H M MichelsRadboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, Netherlands.
Mara van RossumR&D Department, Hycult Biotechnology b.v., Uden, Netherlands.
Aline H de NooijerDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Per H NilssonDepartment of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
Wieke C C de BruinR&D Department, Hycult Biotechnology b.v., Uden, Netherlands.
Erik J M ToonenR&D Department, Hycult Biotechnology b.v., Uden, Netherlands.
Hycult Biotech (Netherlands) · NLRadboud University Medical Center · NLOslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The complement system is an essential component of our innate defense and plays a vital role in the pathogenesis of many diseases. Assessment of complement activation is critical in monitoring both disease progression and response to therapy. Complement analysis requires accurate and standardized sampling and assay procedures, which has proven to be challenging. Objective: We performed a systematic analysis of the current methods used to assess complement components and reviewed whether the identified studies performed their complement measurements according to the recommended practice regarding pre-analytical sample handling and assay technique. Results are supplemented with own data regarding the assessment of key complement biomarkers to illustrate the importance of accurate sampling and measuring of complement components. Methods: A literature search using the Pubmed/MEDLINE database was performed focusing on studies measuring the key complement components C3, C5 and/or their split products and/or the soluble variant of the terminal C5b-9 complement complex (sTCC) in human blood samples that were published between February 2017 and February 2022. The identified studies were reviewed whether they had used the correct sample type and techniques for their analyses. Results: A total of 92 out of 376 studies were selected for full-text analysis. Forty-five studies (49%) were identified as using the correct sample type and techniques for their complement analyses, while 25 studies (27%) did not use the correct sample type or technique. For 22 studies (24%), it was not specified which sample type was used. Conclusion: A substantial part of the reviewed studies did not use the appropriate sample type for assessing complement activation or did not mention which sample type was used. This deviation from the standardized procedure can lead to misinterpretation of complement biomarker levels and hampers proper comparison of complement measurements between studies. Therefore, this study underlines the necessity of general guidelines for accurate and standardized complement analysis.

Indexed as

Complement ActivationComplement C5BiomarkersComplement C3Complement Membrane Attack ComplexHumansBiomarkersComplement C3Complement C5Complement Membrane Attack Complexcomplement activationcomplement diagnosticscomplement systemimmunoassaysstandardization of measurementssystematic review

Identifiers

PMID36330514
PMCPMC9623276
OpenAlexW4306685519

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.