John J Chen1,2, Andrew McKeon2,3,4, Tammy M Greenwood3, Eoin P Flanagan2,3,4, M Tariq Bhatti1,2, Divyanshu Dubey2,3,4, Jose S Pulido1,5, Raymond Iezzi1, Wendy M Smith1, H Nida Sen6, Lynn K Gordon7, Sean J Pittock2,3,4. 1. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. 2. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 4. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. 5. Department of Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania. 6. National Eye Institute, National Institutes of Health, Bethesda, Maryland. 7. Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles.
Abstract
IMPORTANCE: The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria. OBJECTIVE: To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments-certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings. MAIN OUTCOMES AND MEASURES: Results of the autoimmune retinopathy and cancer-associated retinopathy panels. RESULTS: Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments-certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate. CONCLUSIONS AND RELEVANCE: The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.
IMPORTANCE: The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria. OBJECTIVE: To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments-certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings. MAIN OUTCOMES AND MEASURES: Results of the autoimmune retinopathy and cancer-associated retinopathy panels. RESULTS: Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments-certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate. CONCLUSIONS AND RELEVANCE: The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.
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Authors: Jacob S Heng; Jenna M Kim; D Kyle Jones; Kathleen M Stoessel; Sarah A Weiss; Mario Sznol; Harriet M Kluger; Scott D Walter; Niki A Silverstein; Renelle Pointdujour-Lim Journal: BMJ Open Ophthalmol Date: 2022-01-03