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Lynn Hassman, Michelle Warren, Krystel R Huxlin, Mina M Chung, lei xu; Evidence of melanoma immunoreactivity in patients with Birdshot retinochoroidopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5745.
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© ARVO (1962-2015); The Authors (2016-present)
Birdshot retinochoroidopathy (BSRC) is an inflammatory disease characterized by hypopigmented spots in the retina. These spots resemble cutaneous vitiligo, which results from immune-mediated destruction of melanocytes. Vitiligo can arise spontaneously, or in the context of a successful immune response to melanoma. Notably, there are multiple reports of BSRC occurring in patients with a history of melanoma. Given the similarities between BSRC and vitiligo, we tested the hypothesis that BSRC might also be associated with an immune response to melanoma by searching for anti-melanoma antibodies in serum from patients with BSRC.
Serum was obtained from patients with BSRC, as well as from melanoma patients and normal patients without ocular disease or systemic autoimmunity. Importantly, our BSRC patients had no known personal or family history of skin cancer. Western blots were made from melanoma cell lysates and probed with patient or control sera. Lysate from human fibroblasts was also used as a control for non-melanoma autoimmunity.
Thus far, sera from 6 patients with BSRC, 4 patients with melanoma, and 5 normal patients have been analyzed. Prominent bands were seen at 100 kDa, 70 kDa, 55 kDa and 45-50 kDa on blots probed with BSCR patient serum, indicating immunoreactivity to specific proteins present in melanoma cell lysates. The bands were absent or extremely faint on blots probed with normal patient serum, but variably present on blots probed with melanoma patient serum, suggesting a similar immune response in BSRC and melanoma patients.
These results demonstrate the presence of anti-melanoma antibodies in serum from patients with BSRC. While our BSRC patients have no clinical history of melanoma, the presence of these antibodies suggests that they may have had subclinical tumors that were eliminated by a successful immune response. This work suggests that the immune trigger for the HLA-A29-restricted inflammation seen in BSRC may be melanoma, and that BSRC may represent an immune cross-reactivity to melanin-associated antigens in the choroid and RPE. Alternatively, BSRC may trigger an immune response to melanin-associated chorioretinal antigens that cross-react with melanoma cell antigens.
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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