Evidence map›Paper›PMID 40220335›Full record

ArticleRheumatology (Oxford, England)2025

Anti-muscarinic 3 antibodies associate with a severe clinical phenotype in patients with systemic sclerosis.

Ali Y Ayla, Naveen R Kalavar, Mark Pimentel, Walter Morales, Laura K Hummers, Ami A Shah, Michael Hughes, Zsuzsanna H McMahan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
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.

Ali Y AylaDivision of Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0003-2581-7992
Naveen R KalavarDepartment of Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Mark PimentelKarsh Division of Gastroenterology and MAST Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Walter MoralesKarsh Division of Gastroenterology and MAST Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Laura K HummersDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ami A ShahDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael HughesDivision of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, UK.
Zsuzsanna H McMahanDivision of Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-6461-8940

Funding

Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI Antony Rosen · 2016 to 2026
$8.9M
Autoantibodies Define Scleroderma Subgroups with Distinct Relationships to CancerR01AR073208 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI LIVIA A CASCIOLA-ROSEN, Ami Aalok Shah · 2018 to 2026
$5.2M
Interrogating the pathophysiological mechanisms of constipation in patients with systemic sclerosisR01AR081382 · NIAMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Jiande Chen, Zsuzsanna Hortobagyi McMahan · 2023 to 2026
$2.4M
Harnessing multivariate patient- and population-level disease trajectories to predict major clinical events in sclerodermaK24AR080217 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI Ami Aalok Shah · 2022 to 2026
$847k
Scleroderma and Gastrointestinal Disease: Insights into Clinical Phenotypes and Disease PathogenesisK23AR071473 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI MCMAHAN, ZSUZSANNA HORTOBAGYI · 2018 to 2022
$808k
Donald B. and Dorothy L. Stabler FoundationNIAMS NIH HHS 1K23AR071473NIAMS NIH HHS K23 AR071473NIAMS NIH HHS K24 AR080217NIAMS NIH HHS P30 AR070254NIAMS NIH HHS R01 073208NIAMS NIH HHS R01 AR073208NIAMS NIH HHS R01 AR081382NIH
6 · The paper itself

Abstract

objectivesFunctional antibodies play a role in SSc gastrointestinal (GI) disease, but their clinical relevance is unclear. We examined GI and extraintestinal features associated with anti-muscarinic-3 receptor (M3R) antibodies in SSc patients.

methodsIn a cohort enriched for GI symptoms, SSc patients were tested for anti-M3R antibodies using an ELISA. High-titres were defined a priori based on the top quartile of anti-M3R titres to enhance specificity. Clinical features, including high GI severity (Medsger GI Severity Score of ≥2), whole-gut transit study data and UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA GIT 2.0) scores, were compared between patients with and without high-titre anti-M3R antibodies.

resultsIn 132 patients, 52 (39.4%) tested positive for anti-M3R antibodies and 33 (25%) had high-titre anti-M3R antibodies. Compared with patients without high titres, high-titre patients were more likely to have diffuse disease (43.8% vs 22.9%, P = 0.023), high GI severity (90.9% vs 69.7%, P = 0.019), and anti-RNPC3 (18.2% vs 6.1%, P = 0.036) and anti-U1RNP antibodies (21.2 vs 2.0%, P = 0.001). Whole-gut transit studies and UCLA GIT 2.0 scores were not different between the groups. In multivariable logistic regression analysis, high GI severity [odds ratio: 4.50 (95% CI: 1.11, 18.18), P = 0.035] and anti-U1RNP antibodies [odds ratio: 20.36 (95% CI: 3.16, 131.14), P = 0.002] remained associated with high-titre anti-M3R antibodies.

conclusionAnti-M3R antibodies are associated with a more severe GI phenotype and distinct extraintestinal and serological features in SSc patients. Utilizing these features may optimize risk stratification in clinical practice and identify those likely to have progressive GI disease for clinical trials.

Indexed as

AutoantibodiesClinical RelevanceGastrointestinal DiseasesReceptor, Muscarinic M3Scleroderma, SystemicAgedAntibodies, AntinuclearEnzyme-Linked Immunosorbent AssayFemaleHumansLogistic ModelsMaleMiddle AgedOdds RatioPhenotypeProspective StudiesAntibodies, Antinuclearanti-small nuclear ribonucleoproteins autoantibodiesAutoantibodiesReceptor, Muscarinic M3antibodygastrointestinal diseaseM3Rmuscarinicsclerodermasystemic sclerosis

Identifiers

PMID40220335
PMCPMC12494224

What OpenQuestion holds

Textmetadata
LicenceTDM
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.