Autoantibodies contribute to the immunopathogenesis of experimental dry eye disease

Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2062-75. doi: 10.1167/iovs.11-9299.


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

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoantibodies / blood*
  • Autoantigens / immunology*
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology*
  • Complement Activation / immunology
  • Complement C3b / metabolism
  • Disease Models, Animal*
  • Dry Eye Syndromes / immunology*
  • Dry Eye Syndromes / pathology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Immunity, Humoral / physiology
  • Immunization, Passive
  • Immunoglobulin G / immunology
  • Kallikreins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Tissue Kallikreins / immunology*


  • Autoantibodies
  • Autoantigens
  • Immunoglobulin G
  • Complement C3b
  • Kallikreins
  • Klk13 protein, mouse
  • Tissue Kallikreins