Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 1;139(6):658-662.
doi: 10.1001/jamaophthalmol.2021.0651.

Clinical Utility of Antiretinal Antibody Testing

John J Chen  1   2 , Andrew McKeon  2   3   4 , Tammy M Greenwood  3 , Eoin P Flanagan  2   3   4 , M Tariq Bhatti  1   2 , Divyanshu Dubey  2   3   4 , Jose S Pulido  1   5 , Raymond Iezzi  1 , Wendy M Smith  1 , H Nida Sen  6 , Lynn K Gordon  7 , Sean J Pittock  2   3   4
Affiliations

Clinical Utility of Antiretinal Antibody Testing

John J Chen et al. JAMA Ophthalmol. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr McKeon reported receiving grants from Euroimmun outside the submitted work and having patents pending for Septin-5/7-IgGs, MAP1B-IgG, Kelch-like-11-IgG, PDE10A-IgG, GFAP-IgG. Dr Flanagan reported being a site principal investigator in a placebo-controlled randomized clinical trial of inebilizumab (a CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio. He receives no personal compensation and only receives reimbursement for the research activities related to the trial. Dr Dubey reported having a patent for Kelch-like protein 11 pending and has consulted for UCB and Astellas Pharmaceuticals; all compensation for consulting activities is paid directly to Mayo Clinic. Dr Pulido reported having intellectual property via Mayo Clinic and financial interest in Lagen Laboratories and serving on the scientific advisory board of Amydis. Dr Pittock reported serving as codirector of the Mayo Clinic Neuroimmunology Laboratory. No other disclosures were reported.

Figures

Figure.
Figure.. Western Blot at the Mayo Clinic Research Laboratory
The Western blots show multiple bands in most patients, which largely correspond to the molecular weight (MW) of antibodies that were positive at the Clinical Laboratory Improvement Amendments–certified laboratory.
See this image and copyright information in PMC

References

    1. Thirkill CE, Tait RC, Tyler NK, Roth AM, Keltner JL. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci. 1992;33(10):2768-2772. - PubMed
    1. Sen HN, Grange L, Akanda M, Fox A. Autoimmune retinopathy: current concepts and practices (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2017;115:T8. - PMC - PubMed
    1. Grewal DS, Fishman GA, Jampol LM. Autoimmune retinopathy and antiretinal antibodies: a review. Retina. 2014;34(5):827-845. doi:10.1097/IAE.0000000000000119 - DOI - PubMed
    1. Fox AR, Gordon LK, Heckenlively JR, et al. . Consensus on the diagnosis and management of nonparaneoplastic autoimmune retinopathy using a modified Delphi approach. Am J Ophthalmol. 2016;168:183-190. doi:10.1016/j.ajo.2016.05.013 - DOI - PMC - PubMed
    1. Grange L, Dalal M, Nussenblatt RB, Sen HN. Autoimmune retinopathy. Am J Ophthalmol. 2014;157:266-272.e1. doi:10.1016/j.ajo.2013.09.019 - DOI - PMC - PubMed

Publication types