Abstract Details

Title GAD-positive Stiff Person Syndrome (GAD-SPS) with Autoimmune Retinopathy (AR): Argonaute-2 but not GAD as Potential Targeted Retinal Antigen

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 031

Objective Autoimmune retinopathy (AR) is a very bothersome condition seen in some patients with GAD- SPS presenting with severe photophobia and reduced visual acuity. Although connected-but not proven- to expression of GAD in the retina, the cause and treatment of SPS-associated AR are unknown.

Background A 56-year-old woman exhibited gradual vision loss and photophobia followed three years later by stiffness in the right leg and nystagmus associated with very high GAD- ab titers and negative anti-recoverin autoantibodies, consistent with GAD-SPS-SD. Her visual acuity has gradually worsened but visual fields improved after IVIg therapy.

Design/Methods

To explore the cause of AR, we applied single and double immunocytochemistry with her serum along with a monoclonal GAD-ab on monkey retina. Additionally, immunoprecipitation of mouse retina antigens followed by mass spectrometry analysis was performed.

Results The patient’s serum (one year after IVIg), but not sera from 5 other GAD-positive SPS patients without retinopathy, specifically immunostained the photoreceptor layer of monkey retina; surprisingly however, based on double immunocytochemistry with an anti-GAD monoclonal antibody, the retinal layer positively immunostained with the patient’s serum, was GAD-negative. With immunoprecipitation and mass spectrometry using the patient’s serum, but not sera form GAD-SPS patients without retinopathy, an abundance of peptides derived from the intracellular retinal protein argonaute-2 were identified.

Conclusions Some GAD-SPS patients may have AR associated with serum anti-retinal antibodies that recognize non-GAD antigens in the photoreceptor retinal layer. These antibodies seem to target intracellular proteins, highlighted by argonaute-2, based on mass-spectroscopy. The causative role of argonaute-2 protein series is currently further investigated not only for AR but also as a potential antigen in a subset of SPS patients.

Authors/Disclosures
Panos-Alexis Stathopoulos, MD (Eginiteion University of Athens Greece) PRESENTER	Dr. Stathopoulos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. The institution of Dr. Stathopoulos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. Dr. Stathopoulos has received personal compensation in the range of $0-$499 for serving as a Consultant for Medicxi. Dr. Stathopoulos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VIANEX. Dr. Stathopoulos has stock in MABY. The institution of Dr. Stathopoulos has received research support from The Onassis Foundation. Dr. Stathopoulos has received personal compensation in the range of $5,000-$9,999 for serving as a Physician of Clinical Trial with Roche.
Sofia Akrivou	No disclosure on file
Chrysoula Zografou (Yale Univ Sch of Medicine, Dept of Neur)	No disclosure on file
Michael Karampelas	No disclosure on file
Myrto Denaxa	No disclosure on file
Martina Samiotaki	No disclosure on file
Marinos C. Dalakas, MD, FAAN (Thomas Jefferson University)	Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols, . Dr. Dalakas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dysimmune Diseases Foundation. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Therapeutic Advances in Neurology (TAND). Dr. Dalakas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink.

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