Assessing the Impact of Immune Checkpoint Inhibitor Therapy on Disease Activity in Multiple Sclerosis Patients

BackgroundA 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/MethodsTo 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. ResultsThe 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. ConclusionsSome GAD-SPS patients may have AR associated with serum antiretinal 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.Study Supported By: N/A.Disclosure: 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