Evidence map›Paper›PMID 35804445›Full record

ArticleArthritis research & therapy2022

The role of LCN2 and LCN2-MMP9 in spondylitis radiographic development: gender and HLA-B27 status differences.

Florence W L Tsui, Aifeng Lin, Ismail Sari, Zhenbo Zhang, Kenneth P H Pritzker, Hing Wo Tsui, Robert D Inman

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

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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 4 institutions in 2 countries.

Florence W L TsuiDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Aifeng LinKeyIntel Medical Inc., Toronto, Ontario, Canada.
Ismail SariSchroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada.
Zhenbo ZhangKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Kenneth P H PritzkerKeyIntel Medical Inc., Toronto, Ontario, Canada.
Hing Wo TsuiKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Robert D InmanDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada. robert.inman@uhn.ca.
University Health Network · CAUniversity of Toronto · CAArthritis Society · CAKrembil Research Institute

Funding

CIHR FRN:126011
6 · The paper itself

Abstract

backgroundMale HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis.

methodsWe analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed.

resultsIn L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease.

conclusionL and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.

Indexed as

AnkylosisSacroiliitisSpondylarthritisSpondylitis, AnkylosingFemaleHLA-B27 AntigenHumansInflammationLipocalin-2Magnetic Resonance ImagingMaleMatrix Metalloproteinase 9Sacroiliac JointHLA-B27 AntigenLCN2 protein, humanLipocalin-2Matrix Metalloproteinase 9MMP9 protein, humanAxial spondyloarthritisGender differencesHLA-B27 effectLipocalin 2Lipocalin 2-MMP9 complexMRImSASSSSIJ and spinal inflammation

Identifiers

PMID35804445
PMCPMC9264538
OpenAlexW4284882588

What OpenQuestion holds

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LicenceCC BY
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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.