Positive Antiretinal Antibody Tests Common in Patients Without Autoimmune Retinopathy

By Lorraine L. Janeczko

May 12, 2021

NEW YORK (Reuters Health) - Most patients with positive antiretinal antibody test results do not have autoimmune retinopathy, a new study suggests.

Current commercial retinal antibody tests, other than results for antibodies against recoverin, should be interpreted with caution, researchers advise, especially for patients with low clinical suspicion.

"Retinal antibodies (other than recoverin) appear to be more common in normal individuals than previously recognized," Dr. John J. Chen of Mayo Clinic in Rochester, Minnesota, told Reuters Health by email. "Our study found that many patients without autoimmune retinopathy had positive retinal antibodies in their serum. These antibodies were found in two laboratories; therefore, the assays are likely correct."

Recognizing this poor specificity is important in order to avoid treating patients with unnecessary immunosuppressants that can lead to significant extraocular adverse effects, Dr. Chen and his colleagues write in JAMA Ophthalmology.

The researchers conducted a cross-sectional study to evaluate retinal antibody tests available in North America. Over nine months, they recruited 14 patients who did not have autoimmune retinopathy into the Mayo Clinic Neuroimmunology Biorepository. Serum samples were sent according to a masked protocol to a Clinical Laboratory Improvement Amendments-certified laboratory.

To determine the reproducibility of the findings, the Mayo Clinic Neuroimmunology Research Laboratory also assessed the samples, using similar methods.

Although no samples came from patients with autoimmune retinopathy, 13 (93%) samples tested positive for retinal antibodies, for a specificity of 7%. The median number of antibodies per patient was five, with a range of zero to eight.

Confirmatory human retina immunohistochemistry staining was observed in 12 (86%) samples; and alpha-enolase was present in nine (64%). Recoverin was the only retinal antibody that was not detected.

"This study highlights that a diagnosis of autoimmune retinopathy cannot be made on the basis of positive retinal antibodies," Dr. Chen said. "This finding is important because patients are often incorrectly diagnosed with autoimmune retinopathy because of the presence of retinal antibodies. They are treated with chronic immunotherapy, which can have significant side effects for a disease they do not have."

Dr. Lucia Sobrin, a clinician at Massachusetts Eye and Ear and an associate professor of ophthalmology at Harvard Medical School, in Boston, was not surprised by the findings.

"I have seen in my own clinical practice and research that antiretinal antibody testing lacks specificity. I have been referred patients for whom the referring physician had already ordered the antibodies, then sent the patients to me for an opinion as to whether they might have autoimmune retinopathy," said Dr. Sobrin, who was not involved in the study. "In most cases, the patients had positive antiretinal antibodies, yet they ended up being diagnosed with other conditions. This study formally describes and thoroughly documents this phenomenon, which we have seen clinically."

"A positive antiretinal antibody test does not equal autoimmune retinopathy as the diagnosis," Dr. Sobrin noted by email. "Autoimmune retinopathy is primarily a clinical diagnosis. Because of the poor specificity of the test, the presence of antiretinal antibodies, with perhaps the exception of recoverin, does not contribute significantly to the diagnosis."

"This paper is an important contribution to our ability to interpret antiretinal antibody results appropriately," she added. "It will raise awareness about the pitfalls and limitations of antiretinal antibody testing."

Dr. Chen acknowledged that, while a strength of the study is its masked protocol, its main limitation is its small sample size.

He would like to see more robust assays and validation to better identify retinal antibodies specific to autoimmune retinopathy.

"Larger studies will be required to help determine in what scenarios these retinal antibodies may be helpful clinically," he said.

SOURCE: https://bit.ly/3baSVYL JAMA Ophthalmology, online April 22, 2021.