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Steven K Lundy, Athanasios J Karoukis, Ray Ohara, Enayat Nikoopour, Mohammad I Othman, Maria Fernanda Abalem, Thiran Jayasundera, Kari E Branham, John R Heckenlively; Importance of Checking for Active Autoimmunity in Genetically-Confirmed Retinal Dystrophy Patients. Invest. Ophthalmol. Vis. Sci. 2017;58(8):556.
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Anti-retinal antibodies (ARA) have been found in patients with retinal dystrophies, and used as a lab diagnostic tool to detect retinal autoimmunity. The importance of this to patient care is that immune suppressive treatment can often slow progression of retinal degeneration that is greatly accelerated by autoimmunity. However, the methods usually used to detect ARA do not provide information about the pathogenesis or current activity of the disease. We have set out to define more robust criteria for active retinal autoimmunity and to discover clues to the mechanisms involved in immune-mediated retinal degeneration.
We randomly selected a set of 49 consented patients with genetically confirmed retinal dystrophies. Blood samples underwent an extensive immune profile consisting of standard measurement of ARA by Western blot, as well as detection of anti-recoverin IgG and IgM antibodies by ELISA. Recoverin-induced cytokine (IFNγ, TNFα and IL-10) production by patient peripheral blood mononuclear cells was analyzed by ELISA. Immune cell lineages and activation status were compared using four 10-color flow cytometry panels. Whole blood mRNA was isolated to measure gene expression using NanoStringTM assays. Comparisons were made to define autoimmune and non-autoimmune dystrophy patients.
We used several criteria to classify patients as autoreactive consisting of: 1) three or more ARA; 2) a high titer of recoverin-specific IgG or IgM; and/or 3) very high production of IFNγ or TNFα in response to recoverin. The data summarized in the table show the number of patients meeting each of the criteria. We found that 28/49 (57%) of dystrophy patients had elevated anti-recoverin antibody titers or inflammatory cytokine responses. These parameters closely correlated with disease activity and were sensitive to treatment with immune suppression. High levels of natural killer cells (>30%) and B lymphocytes (>20%) were frequently found in the blood of autoimmune patients but not the non-autoimmune group. Immune cell activation and gene expression in the patients were also affected by treatments, but the patterns of ARA were not altered in most of the treated patients.
Retinal dystrophies sometimes have comorbidity associated with autoimmunity. Cellular and humoral immune responses against recoverin mark disease activity and can be favorably altered by immune suppressive treatment.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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