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, Stephen C. Pflugfelder

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)2062-2075
Number of pages14
JournalInvestigative ophthalmology & visual science
Volume53
Issue number4
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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