Immune Response Targeting Sjögren's Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice

Int J Mol Sci. 2018 Sep 27;19(10):2935. doi: 10.3390/ijms19102935.


Autoantibodies reactive against Ro52 are present in 70% of Sjögren's syndrome patients and are associated with higher disease severity. However, their role in causing aqueous deficient dry eye, a major cause for morbidity in Sjögren's syndrome, is unclear. To investigate whether immune responses targeting Ro52 contribute towards the dry eye, male and female NZM2758 mice were immunized with recombinant Ro52. Tear production was measured by the phenol red thread test. Sera were analyzed for anti-Ro52 levels by immunoprecipitation. Lacrimal glands were evaluated for inflammatory foci and IgG deposits. Our results showed that, although all mice generated anti-Ro52 antibodies, only females developed a significant drop in tear production. None of the mice developed severe lacrimal gland inflammation, and female mice with anti-Ro52 showed higher levels of IgG deposits within their glands. Passive transfer of anti-Ro52 sera caused reduced tear production in female mice, but not in males. This study demonstrates for the first time that immune responses initiated by Ro52 induce aqueous dry eye, and this may be driven by anti-Ro52 antibodies. Furthermore, the sexual dimorphism in glandular dysfunction suggests that the lacrimal glands in females are more susceptible to autoantibody-mediated injury.

Keywords: Ro52; Sjögren’s syndrome; dry eye; lacrimal gland; sexual dimorphism.

MeSH terms

  • Animals
  • Female
  • Immunoglobulin G / immunology
  • Inflammation
  • Lacrimal Apparatus / immunology*
  • Lacrimal Apparatus / physiopathology
  • Male
  • Mice
  • Ribonucleoproteins / immunology*
  • Sex Factors
  • Sjogren's Syndrome / immunology*


  • Immunoglobulin G
  • Ribonucleoproteins
  • SS-A antigen