Evidence map›Paper›PMID 33974929›Full record

ArticleThe Journal of allergy and clinical immunology2022

Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease.

Justin A Jarrell, Matthew C Baker, Cory A Perugino, Hang Liu, Michelle S Bloom, Takashi Maehara, Heidi H Wong, Tobias V Lanz, Julia Z Adamska, Sarah Kongpachith and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth.medRxiv : the preprint server for health sciences · 2025
    Article
  5. Article
  6. Omics in IgG4-related disease.Chinese medical journal · 2025
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. IL-1RA autoantibodies: insights into mechanisms and associated diseases.American journal of translational research · 2024
    Review
  12. Review
  13. Immune dysregulation in immunoglobulin G4-related disease.The Japanese dental science review · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

14 authors at 5 institutions in 3 countries.

Justin A JarrellDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
Matthew C BakerDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif.
Cory A PeruginoMassachusetts General Hospital, Harvard Medical School, Boston, Mass.
Hang LiuMassachusetts General Hospital, Harvard Medical School, Boston, Mass.
Michelle S BloomDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
Takashi MaeharaMassachusetts General Hospital, Harvard Medical School, Boston, Mass.
Heidi H WongDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
Tobias V LanzDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif; Department of Neurology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Julia Z AdamskaDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
Sarah KongpachithDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
Jeremy SokoloveDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif.
John H StoneMassachusetts General Hospital, Harvard Medical School, Boston, Mass.
Shiv S PillaiMassachusetts General Hospital, Harvard Medical School, Boston, Mass.
William H RobinsonDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, Calif; Institute for Immunity, Transplant and Infection, Stanford University, Stanford, Calif; VA Palo Alto Health Care System, Palo Alto, Calif. Electronic address: w.robinson@stanford.edu.
Stanford University · USHarvard University · USInstitute of Infection and Immunity · CAMassachusetts General Hospital · USVA Palo Alto Health Care System · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
The importance of the IgG4 glycome in IgG4-related disease(s)U19AI110495 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SHIV Subramaniam PILLAI · 2014 to 2026
$7.9M
Research Training in Rheumatology at Massachusetts General HospitalT32AR007258 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI ANDREW D LUSTER · 1986 to 2026
$6.9M
Training Program in Adult and Pediatric RheumatologyT32AR050942 · NIAMS · STANFORD UNIVERSITY · PI LEWIS, DAVID BRAM, ROBINSON, WILLIAM H · 2005 to 2025
$6.6M
Large-Scale Characterization of Autoantibody Responses in Rheumatoid ArthritisR01AR063676 · NIAMS · STANFORD UNIVERSITY · PI ROBINSON, WILLIAM H · 2013 to 2017
$1.7M
Targeting T cell Subsets in Autoimmune DiseaseUM1AI144295 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI John H Stone · 2019 to 2026
$1.4M
NIAID NIH HHS T32 AI007290NIAID NIH HHS U19 AI110495NIAID NIH HHS UM1 AI144295NIAMS NIH HHS R01 AR063676NIAMS NIH HHS T32 AR007258NIAMS NIH HHS T32 AR050942NIDDK NIH HHS P30 DK043351
6 · The paper itself

Abstract

backgroundIgG4-related disease (IgG4-RD) is a fibroinflammatory condition involving loss of B-cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined.

objectiveOur aim was to identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD.

methodsWe sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative mAbs were expressed and their specificities characterized by using cytokine microarrays. The role of anti-IL-1 receptor antagonist (IL-1RA) autoantibodies was investigated by using in vitro assays.

resultsWe identified strong reactivity against human IL-1RA by using a clonally expanded plasmablast-derived mAb from a patient with IgG4-RD. Plasma from patients with IgG4-RD exhibited elevated levels of reactivity against IL-1RA compared with plasma from the controls and neutralized IL-1RA activity, resulting in inflammatory and fibrotic mediator production in vitro. IL-1RA was detected in lesional tissues from patients with IgG4-RD. Patients with anti-IL-1RA autoantibodies of the IgG4 subclass had greater numbers of organs affected than did those without anti-IL-1RA autoantibodies. Peptide analyses identified IL-1RA epitopes targeted by anti-IL-1RA antibodies at sites near the IL-1RA/IL-1R interface. Serum from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also had elevated levels of anti-IL-1RA autoantibodies compared with those of the controls.

conclusionA subset of patients with IgG4-RD have anti-IL-1RA autoantibodies, which promote proinflammatory and profibrotic meditator production via IL-1RA neutralization. These findings support a novel immunologic mechanism underlying the pathogenesis of IgG4-RD. Anti-IL-1RA autoantibodies are also present in a subset of patients with SLE and RA, suggesting a potential common pathway in multiple autoimmune diseases.

Indexed as

AdolescentAdultAgedAged, 80 and overAntibodies, NeutralizingArthritis, RheumatoidAutoantibodiesAutoantigensChildChild, PreschoolFemaleFibrosisHumansImmunoglobulin GLupus Erythematosus, SystemicMaleAntibodies, NeutralizingAutoantibodiesAutoantigensImmunoglobulin GReceptors, Interleukin-1autoantibodiesautoimmune diseasecytokineIgG4-related diseaseIL-1 receptor antagonistlupusplasmablastrheumatoid arthritissequencing

Identifiers

PMID33974929
PMCPMC8573062
OpenAlexW3161916665

What OpenQuestion holds

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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.