Evidence map›Paper›PMID 38231276›Full record

ArticleJournal of clinical immunology2024

Autoantibody-Mediated Depletion of IL-1RA in Still's Disease and Potential Impact of IL-1 Targeting Therapies.

Marie-Christin Hoffmann, Giulio Cavalli, Natalie Fadle, Eleonora Cantoni, Evi Regitz, Octavian Fleser, Philipp Klemm, Marina Zaks, Elisabeth Stöger, Corrado Campochiaro and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth.medRxiv : the preprint server for health sciences · 2025
    Article
  6. Article
  7. Article
  8. IL-1 receptor antagonist: etiological and drug delivery systems overview.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    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

24 authors at 9 institutions in 2 countries.

Marie-Christin HoffmannJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Giulio CavalliVita-Salute San Raffaele University, Milan, Italy.
Natalie FadleJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Eleonora CantoniVita-Salute San Raffaele University, Milan, Italy.
Evi RegitzJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Octavian FleserJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Philipp KlemmDepartment of Rheumatology, Immunology, Osteology and Physical Medicine, Justus-Liebig-University Gießen, Campus Kerckhoff, Bad Nauheim, Germany.
Marina ZaksDepartment of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.
Elisabeth StögerEvangelische Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung Essen-Huttrop, Essen, Germany.
Corrado CampochiaroVita-Salute San Raffaele University, Milan, Italy.
Alessandro TomelleriVita-Salute San Raffaele University, Milan, Italy.
Elena BaldisseraVita-Salute San Raffaele University, Milan, Italy.
Jörg Thomas BittenbringJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Vincent ZimmerDepartment of Internal Medicine, Knappschaftsklinikum Saar, Püttlingen, Germany.
Jochen PfeiferDepartment of Pediatric Cardiology, Saarland University, Homburg, Germany.
Yvan FischerInstitute of Physiology, Medical Faculty, RWTH Aachen, 52057, Aachen, Germany.
Klaus-Dieter PreussJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Moritz BewarderJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany.
Bernhard ThurnerMedizinisches Versorgungszentrum, Mindelheim, Germany.
Sabrina FuehnerDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Münster, Germany.
Dirk FoellDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Münster, Germany.
Lorenzo DagnaVita-Salute San Raffaele University, Milan, Italy.
Christoph KesselDepartment of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Münster, Germany.
Lorenz ThurnerJosé Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, 66421, Homburg, Saarland, Germany. lorenz.thurner@uks.eu.ORCID 0000-0002-8167-2989
Saarland University · DEVita-Salute San Raffaele University · ITUniversity Hospital Münster · DECenter for HIV and Hepatogastroenterology · DECharité - Universitätsmedizin Berlin · DEJustus-Liebig-Universität Gießen · DEKliniken Essen-Mitte · DEKnappschaftsklinikum Saar · DERWTH Aachen University · DE

Funding

Universität des Saarlandes BioNanoMed
6 · The paper itself

Abstract

backgroundAdult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) resemble a continuum of a rare, polygenic IL-1β-driven disease of unknown etiology.

objectiveIn the present study we sought to investigate a potential role of recently described autoantibodies neutralizing the interleukin-1(IL-1)-receptor antagonist (IL-1-Ra) in the pathogenesis of Still's disease.

methodsSerum or plasma samples from Still's disease patients (AOSD, n = 23; sJIA, n = 40) and autoimmune and/or inflammatory disease controls (n = 478) were analyzed for autoantibodies against progranulin (PGRN), IL-1Ra, IL-18 binding protein (IL-18BP), and IL-36Ra, as well as circulating IL-1Ra and IL-36Ra levels by ELISA. Biochemical analyses of plasma IL-1Ra were performed by native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1β-signaling reporter assay.

resultsAnti-IL-1-Ra IgG were identified in 7 (27%) out of 29 Still's disease patients, including 4/23 with AOSD and 3/6 with sJIA and coincided with a hyperphosphorylated isoform of endogenous IL-1Ra. Anti-IL-36Ra antibodies were found in 2 AOSD patients. No anti-PGRN or anti-IL-18BP antibodies were detected. Selective testing for anti-IL-1Ra antibodies in an independent cohort (sJIA, n = 34) identified 5 of 34 (14.7%) as seropositive. Collectively, 8/12 antibody-positive Still's disease patients were either new-onset active disease or unresponsive to IL-1 blocking drugs. Autoantibody-seropositivity associated with decreased IL-1Ra plasma/serum levels. Seropositive plasma impaired in vitro IL-1Ra bioactivity, which could be reversed by anakinra or canakinumab treatment.

conclusionAutoantibodies neutralizing IL-1Ra may represent a novel patho-mechanism in a subgroup of Still's disease patients, which is sensitive to high-dose IL-1 blocking therapy.

Indexed as

Arthritis, JuvenileInterleukin 1 Receptor Antagonist ProteinAutoantibodiesEnzyme-Linked Immunosorbent AssayHumansInterleukin-1betaAutoantibodiesInterleukin-1betaInterleukin 1 Receptor Antagonist ProteinAdult-onset Still’s disease (AOSD)Anti-IL-1Ra autoantibodiesStill’s diseaseSystemic juvenile idiopathic arthritis (sJIA)

Identifiers

PMID38231276
PMCPMC10794369
OpenAlexW4390946572

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.