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Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice
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 tar...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213551/ https://www.ncbi.nlm.nih.gov/pubmed/30261673 http://dx.doi.org/10.3390/ijms19102935 |
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author | Trzeciak, Marta Bagavant, Harini Papinska, Joanna Deshmukh, Umesh S. |
author_facet | Trzeciak, Marta Bagavant, Harini Papinska, Joanna Deshmukh, Umesh S. |
author_sort | Trzeciak, Marta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6213551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62135512018-11-14 Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice Trzeciak, Marta Bagavant, Harini Papinska, Joanna Deshmukh, Umesh S. Int J Mol Sci Article 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. MDPI 2018-09-27 /pmc/articles/PMC6213551/ /pubmed/30261673 http://dx.doi.org/10.3390/ijms19102935 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Trzeciak, Marta Bagavant, Harini Papinska, Joanna Deshmukh, Umesh S. Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title | Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title_full | Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title_fullStr | Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title_full_unstemmed | Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title_short | Immune Response Targeting Sjögren’s Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice |
title_sort | immune response targeting sjögren’s syndrome antigen ro52 suppresses tear production in female mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213551/ https://www.ncbi.nlm.nih.gov/pubmed/30261673 http://dx.doi.org/10.3390/ijms19102935 |
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