Evidence map›Paper›PMID 22395876›Full record

ArticleInvestigative ophthalmology & visual science2012

Autoantibodies contribute to the immunopathogenesis of experimental dry eye disease.

Michael E Stern, Chris S Schaumburg, Karyn F Siemasko, Jianping Gao, Larry A Wheeler, Devin A Grupe, Cintia S De Paiva, Virginia L Calder, Margarita Calonge, Jerry Y Niederkorn and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.7field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
  2. Article
  3. CD4Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Review
  5. Review
  6. Dry Eye Disease: What Is the Role of Vitamin D?International journal of molecular sciences · 2023
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Inflammatory basis for dry eye disease flares.Experimental eye research · 2020
    Review
  20. Article
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

11 authors at 4 institutions in 3 countries.

Michael E SternAllergan, Inc, Biological Sciences, Inflammation Research Program, Irvine, California 92612, USA. stern_michael@allergan.com
Chris S Schaumburg
Karyn F Siemasko
Jianping Gao
Larry A Wheeler
Devin A Grupe
Cintia S De Paiva
Virginia L Calder
Margarita Calonge
Jerry Y Niederkorn
Stephen C Pflugfelder
Ocular Surface Center · USBaylor College of Medicine · USThe University of Texas Southwestern Medical Center · USUniversity College London · GB

Funding

THE IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSR01EY007641 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI NIEDERKORN, JERRY · 1988 to 2016
$5.6M
Core Grant for Vision ResearchP30EY020799 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI NIEDERKORN, JERRY · 2010 to 2016
$4.1M
NEI NIH HHS P30 EY020799NEI NIH HHS R01 EY007641
6 · The paper itself

Abstract

purposeThe purpose of this study was to determine if autoantibodies play a role in the immunopathogenesis of experimental dry eye disease.

methodsDry eye was induced by exposing female C57BL/6 wild-type mice or hen egg lysozyme B-cell receptor transgenic mice to desiccating stress (subcutaneous scopolamine [0.5 mg/0.2 mL] 3 times a day, humidity < 40%, and sustained airflow) for 3 weeks, allowing sufficient time for a humoral immune response. Serum or purified IgG isolated from dry-eye mice or untreated controls was passively transferred to nude recipient mice, which were evaluated for ocular surface inflammation 3 days after transfer. To determine if complement activation contributed to serum-induced dry eye disease, cobra venom factor was used to deplete complement activity.

resultsAutoantibodies against kallikrein 13 were identified in serum from dry-eye mice, but were undetectable in untreated controls. Autoantibody-containing serum or purified IgG from dry-eye mice was sufficient to mediate complement-dependent ocular surface inflammation. Serum or purified IgG caused marked inflammatory burden and tissue damage within the ocular surface tissues, including elevated Gr1+ neutrophil infiltration and proinflammatory cytokines/chemokines associated with goblet cell loss. Moreover, complement C3b deposition was found within the ocular surface tissues of mice receiving dry-eye serum, but not in recipients of control serum. Functionally, complement depletion attenuated the ability to transfer dry-eye-specific serum or IgG-mediated disease.

conclusionsThese data demonstrate for the first time a complement-dependent pathogenic role of dry-eye-specific autoantibodies, and suggest autoantibody deposition within the ocular surface tissues contributes to the predominantly T-cell-mediated immunopathogenesis of dry eye disease.

Indexed as

Disease Models, AnimalAdoptive TransferAnimalsAutoantibodiesAutoantigensBlotting, WesternCD4-Positive T-LymphocytesComplement ActivationComplement C3bDry Eye SyndromesFemaleFluorescent Antibody Technique, IndirectImmunity, HumoralImmunization, PassiveImmunoglobulin GKallikreinsAutoantibodiesAutoantigensComplement C3bImmunoglobulin GKallikreinsKlk13 protein, mouseTissue Kallikreins

Identifiers

PMID22395876
PMCPMC6713471
OpenAlexW1971369241

What OpenQuestion holds

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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.