June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Loss of Natural Immune Tolerance Toward Recoverin in Patients with Autoimmune Retinopathy
Author Affiliations & Notes
  • Steven Lundy
    Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI
  • John R Heckenlively
    Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, Ann Arbor, MI
  • Footnotes
    Commercial Relationships Steven Lundy, None; John Heckenlively, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 865. doi:
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      Steven Lundy, John R Heckenlively; Loss of Natural Immune Tolerance Toward Recoverin in Patients with Autoimmune Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):865.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Autoimmune retinopathy (AIR) leads to a rapid degeneration of visual fields that is distinct from retinitis pigmentosa and correlates with increases in anti-retinal autoantibodies. When properly diagnosed, a majority of patients with active AIR respond to immune suppression with stabilized or improved vision. The pathogenesis of AIR is under investigation to better define the immune response toward retinal antigens, facilitate diagnosis, and help tailor treatments.

 
Methods
 

The cellular and humoral immune response toward the retinal protein recoverin was measured in AIR patients and compared to control subjects. Peripheral blood mononuclear cells (PBMC) from patients and controls were stimulated with recombinant human recoverin and analyzed for the release of interferon gamma (IFNγ) and interleukin 10 (IL-10). Plasma was screened for anti-recoverin antibodies of IgM and IgG subclasses by ELISA. Lymphocyte subsets in peripheral blood were analyzed by flow cytometry.

 
Results
 

Control subject PBMC responded to recoverin by producing a high level of the immune suppressive cytokine IL-10, suggesting a normal role of recoverin in maintaining retinal tolerance. AIR patient PBMC responded to recoverin with significantly lower levels of IL-10 but elevated levels of TH1-associated IFNγ when compared to controls. AIR patients were frequently positive for anti-recoverin IgG with IgG1 being the most dominant subtype. In contrast, controls frequently had measurable titers of circulating anti-recoverin IgM with low or no presence of anti-recoverin IgG antibodies. AIR patients also consistently had a reduced level of CD24highCD38high regulatory B lymphocytes in comparison to controls.

 
Conclusions
 

The high levels of anti-recoverin IgM and IL-10 producing lymphocytes specific toward recoverin in control subjects suggest that this protein is an immune tolerizing retinal antigen. These data support our working hypothesis that the switch from immune tolerance toward recoverin to a more inflammatory TH1-driven response plays an important role in the pathogenesis of AIR. Further studies are in progress to determine correlations between these parameters, disease activity and response to therapy. This information should help improve the diagnosis of AIR and will hopefully lead to significant advances in treatment.  

 
Numerical values are P values from Student's t test for controls (n = 12) versus AIR patients (n = 16).
 
Numerical values are P values from Student's t test for controls (n = 12) versus AIR patients (n = 16).
 

 
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