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Concordance of Antiretinal Antibody Testing Results Between Laboratories in Autoimmune Retinopathy

Concordance of Antiretinal Antibody Testing Results Between Laboratories in Autoimmune Retinopathy The diagnosis of autoimmune retinopathy (AIR) is primarily based on clinical examination and abnormal electroretinographic and visual field testing findings. Antiretinal antibody (ARA) detection is used to support the diagnosis, but its interpretation is limited by our incomplete understanding of which ARAs are pathogenic and the lack of uniform laboratory methods. Western blot is one ARA detection method that is not standardized.1-4 To determine whether different laboratory techniques affect results in a real-life setting, we compared ARA results from 2 laboratories in patients with AIR. Methods We identified patients from the Massachusetts Eye and Ear Infirmary Uveitis and Retina Services who were suspected to have AIR (January 1, 2008, to January 31, 2012). The diagnosis of AIR was based on characteristic symptoms and findings, abnormal electroretinographic findings, and no history of hereditary retinal disease. We included only those patients who had serum samples sent for ARA Western blot testing simultaneously by 2 laboratories (referred to as laboratory A and laboratory B) that accept samples from outside their own institutions. Sample shipment and handling were performed identically for both laboratories. Laboratory A used human retinal extract with positive controls (serum samples containing a known ARA) and negative controls (using only secondary antibody). Laboratory B used pig retinal extract with normal controls (serum samples of people with no ARA activity). We examined the interlaboratory concordance for any ARA detection and for same-size (within 1 kDa) ARA detection. Results The study included 5 men and 9 women (Table). The mean age was 60 years (range, 33-86 years). Nine patients had ARA detected by both laboratories, yielding an overall concordance rate of 64%. Of the 5 patients with discordant results, 4 had ARA detected by laboratory A but not laboratory B and 1 had ARA detected by laboratory B but not laboratory A. Table. Diagnosis, Clinical and Electroretinographic Findings, and Antiretinal Antibody Testing Results in Patients Suspected to Have Autoimmune Retinopathy Table. Diagnosis, Clinical and Electroretinographic Findings, and Antiretinal Antibody Testing Results in Patients Suspected to Have Autoimmune Retinopathy View LargeDownload Among the 9 patients for whom both laboratories detected ARA, 5 had concordant results for the size of at least 1 ARA band. Therefore, the ARA-specific concordance rate was 36%. Even among these 5 cases in which there was 1 common ARA band detected, 4 patients had additional ARAs detected by one laboratory but not the other (patients 2, 3, 9, and 10). Comment Our study shows that different ARA detection techniques lead to different results in a real-life setting, with only 36% of patients having ARA-specific concordance at 2 commonly used laboratories. This observed discrepancy could affect patient management. For example, in some cases, sending the sample to only 1 laboratory in isolation would have yielded a negative result from one laboratory, potentially leading the physician away from the AIR diagnosis, but a positive result from the other laboratory, potentially leading to treatment with immunosuppressants. This study is limited by the lack of a gold standard against which the Western blot accuracy can be evaluated. The use of human retinal extract by laboratory A might lead to higher sensitivity, explaining in part why that laboratory generally detected more ARA more often. Without a gold standard, it is not possible to make any conclusions. However, these results do support the importance of understanding the methods used by a chosen laboratory so that the physician can interpret results more critically. Our current clinical practice is to send serum samples to at least 2 different laboratories simultaneously. If the laboratories detect the same antibodies, we consider this supportive evidence for the diagnosis. In the future, the ability to use ARA testing to confirm AIR diagnoses will depend not only on increased knowledge of pathogenic ARAs but also on establishing standardized methods across laboratories that produce consistent results. Back to top Article Information Correspondence: Dr Sobrin, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (lucia_sobrin@meei.harvard.edu). Author Contributions: Dr Sobrin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures: None reported. Funding/Support: This work was supported by grant EY16335-02 from the National Institutes of Health, a Career Development Award from Research to Prevent Blindness, a Harvard Catalyst Faculty Development and Diversity Faculty Fellowship, and an Eleanor and Miles Shore 50th Anniversary Fellowship. References 1. Thirkill CE. Cancer-induced, immune-mediated ocular degenerations. Ocul Immunol Inflamm. 2005;13(2-3):119-13116019671PubMedGoogle ScholarCrossref 2. Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005;139(5):780-79415860281PubMedGoogle ScholarCrossref 3. Forooghian F, Macdonald IM, Heckenlively JR, et al. The need for standardization of antiretinal antibody detection and measurement. Am J Ophthalmol. 2008;146(4):489-49518672221PubMedGoogle ScholarCrossref 4. Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol. 2008;30(2):127-13418408929PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Ophthalmology American Medical Association

Concordance of Antiretinal Antibody Testing Results Between Laboratories in Autoimmune Retinopathy

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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6165
eISSN
2168-6173
DOI
10.1001/jamaophthalmol.2013.574
Publisher site
See Article on Publisher Site

Abstract

The diagnosis of autoimmune retinopathy (AIR) is primarily based on clinical examination and abnormal electroretinographic and visual field testing findings. Antiretinal antibody (ARA) detection is used to support the diagnosis, but its interpretation is limited by our incomplete understanding of which ARAs are pathogenic and the lack of uniform laboratory methods. Western blot is one ARA detection method that is not standardized.1-4 To determine whether different laboratory techniques affect results in a real-life setting, we compared ARA results from 2 laboratories in patients with AIR. Methods We identified patients from the Massachusetts Eye and Ear Infirmary Uveitis and Retina Services who were suspected to have AIR (January 1, 2008, to January 31, 2012). The diagnosis of AIR was based on characteristic symptoms and findings, abnormal electroretinographic findings, and no history of hereditary retinal disease. We included only those patients who had serum samples sent for ARA Western blot testing simultaneously by 2 laboratories (referred to as laboratory A and laboratory B) that accept samples from outside their own institutions. Sample shipment and handling were performed identically for both laboratories. Laboratory A used human retinal extract with positive controls (serum samples containing a known ARA) and negative controls (using only secondary antibody). Laboratory B used pig retinal extract with normal controls (serum samples of people with no ARA activity). We examined the interlaboratory concordance for any ARA detection and for same-size (within 1 kDa) ARA detection. Results The study included 5 men and 9 women (Table). The mean age was 60 years (range, 33-86 years). Nine patients had ARA detected by both laboratories, yielding an overall concordance rate of 64%. Of the 5 patients with discordant results, 4 had ARA detected by laboratory A but not laboratory B and 1 had ARA detected by laboratory B but not laboratory A. Table. Diagnosis, Clinical and Electroretinographic Findings, and Antiretinal Antibody Testing Results in Patients Suspected to Have Autoimmune Retinopathy Table. Diagnosis, Clinical and Electroretinographic Findings, and Antiretinal Antibody Testing Results in Patients Suspected to Have Autoimmune Retinopathy View LargeDownload Among the 9 patients for whom both laboratories detected ARA, 5 had concordant results for the size of at least 1 ARA band. Therefore, the ARA-specific concordance rate was 36%. Even among these 5 cases in which there was 1 common ARA band detected, 4 patients had additional ARAs detected by one laboratory but not the other (patients 2, 3, 9, and 10). Comment Our study shows that different ARA detection techniques lead to different results in a real-life setting, with only 36% of patients having ARA-specific concordance at 2 commonly used laboratories. This observed discrepancy could affect patient management. For example, in some cases, sending the sample to only 1 laboratory in isolation would have yielded a negative result from one laboratory, potentially leading the physician away from the AIR diagnosis, but a positive result from the other laboratory, potentially leading to treatment with immunosuppressants. This study is limited by the lack of a gold standard against which the Western blot accuracy can be evaluated. The use of human retinal extract by laboratory A might lead to higher sensitivity, explaining in part why that laboratory generally detected more ARA more often. Without a gold standard, it is not possible to make any conclusions. However, these results do support the importance of understanding the methods used by a chosen laboratory so that the physician can interpret results more critically. Our current clinical practice is to send serum samples to at least 2 different laboratories simultaneously. If the laboratories detect the same antibodies, we consider this supportive evidence for the diagnosis. In the future, the ability to use ARA testing to confirm AIR diagnoses will depend not only on increased knowledge of pathogenic ARAs but also on establishing standardized methods across laboratories that produce consistent results. Back to top Article Information Correspondence: Dr Sobrin, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (lucia_sobrin@meei.harvard.edu). Author Contributions: Dr Sobrin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures: None reported. Funding/Support: This work was supported by grant EY16335-02 from the National Institutes of Health, a Career Development Award from Research to Prevent Blindness, a Harvard Catalyst Faculty Development and Diversity Faculty Fellowship, and an Eleanor and Miles Shore 50th Anniversary Fellowship. References 1. Thirkill CE. Cancer-induced, immune-mediated ocular degenerations. Ocul Immunol Inflamm. 2005;13(2-3):119-13116019671PubMedGoogle ScholarCrossref 2. Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005;139(5):780-79415860281PubMedGoogle ScholarCrossref 3. Forooghian F, Macdonald IM, Heckenlively JR, et al. The need for standardization of antiretinal antibody detection and measurement. Am J Ophthalmol. 2008;146(4):489-49518672221PubMedGoogle ScholarCrossref 4. Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol. 2008;30(2):127-13418408929PubMedGoogle ScholarCrossref

Journal

JAMA OphthalmologyAmerican Medical Association

Published: Jan 1, 2013

References

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