Evidence map›Paper›PMID 35296708›Full record

ArticleScientific reports2022

Natural antibodies and CRP drive anaphylatoxin production by urate crystals.

Anne Kathrin Wessig, Leonie Hoffmeister, Annika Klingberg, Anika Alberts, Andreas Pich, Korbinian Brand, Torsten Witte, Konstantin Neumann

Open access · greenAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

13 citing papers in PubMed, 4 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Anne Kathrin WessigInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany.
Leonie HoffmeisterInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany.
Annika KlingbergInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany.
Anika AlbertsInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany.
Andreas PichResearch Core Unit Proteomics & Institute of Toxicology, Hannover Medical School, 30625, Hannover, Germany.
Korbinian BrandInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany.
Torsten WitteDepartment of Rheumatology and Immunology, Hannover Medical School, 30625, Hannover, Germany.
Konstantin NeumannInstitute of Clinical Chemistry, Hannover Medical School, 30625, Hannover, Germany. Neumann.Konstantin@mh-hannover.de.
Medizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In gout, crystallization of uric acid in the form of monosodium urate (MSU) leads to a painful inflammatory response. MSU crystals induce inflammation by activating the complement system and various immune cell types, and by inducing necrotic cell death. We previously found that the soluble pattern recognition molecule C-reactive protein (CRP) recognizes MSU crystals, while enhancing complement activation. In the absence of CRP, MSU crystals still induced complement activation, suggesting additional CRP-independent mechanisms of complement activation. In the present study, we searched for additional MSU crystal-binding complement activators. We found that all healthy individuals, even unborn children, have MSU crystal-specific immunoglobulin M (IgM) in their blood. This indicates that innate IgM, also known as natural IgM, recognizes these crystals. In serum lacking IgM and CRP, MSU crystals showed negligible complement activation as assessed by the production of the anaphylatoxins C4a, C3a, and C5a (listed in order of production via the classical complement pathway). We show that IgM and CRP both activate the classical complement pathway on MSU crystals. CRP was more efficient at fixating active C1 on the crystals and inducing release of the most inflammatory anaphylatoxin C5a, indicating non-redundant functions of CRP. Notably, while CRP recognizes MSU crystals but not the related calcium pyrophosphate dihydrate (CPPD) crystals, natural IgM bound to both, suggesting common and distinct mechanisms of recognition of individual crystal types by complement activators.

Indexed as

GoutUric AcidAnaphylatoxinsC-Reactive ProteinHumansImmunoglobulin MReceptors, ImmunologicAnaphylatoxinsC-Reactive ProteinCRP protein, humanImmunoglobulin MReceptors, ImmunologicUric Acid

Identifiers

PMID35296708
PMCPMC8924570
OpenAlexW4221107543

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Registered trials

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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.