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Characterization of autoimmune eye disease in association with Down’s syndrome

Eye volume 38, pages 386–392 (2024)Cite this article

Subjects

Abstract

Background

Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor.

Subjects/methods

This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory.

Results

We characterized eight subjects (mean age 29 [range, 19–37] years). The mean age of detected uveitis onset was 23.5 [range, 11–33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase.

Discussion

A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

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Fig. 1: Representative ophthalmic imaging.

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Data availability

The data in this manuscript are primarily deidentified patient information contributed by all authors except GA. The first author, AMR (amr@dal.ca), can be contacted about access to deidentified data.

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Acknowledgements

We would like to acknowledge Lindsey Watson and Tammy Martin for their assistance with the ethics board approval process.

Funding

NIH RO1 EY026572, P30 EY010572, the Grandmaison Fund for Autoimmunity Research, the Stan and Madelle Rosenfeld Family Trust, the William and Mary Bauman Foundation, and Research to Prevent Blindness. JTR receives support from the Rheumatology Research Foundation of the American College of Rheumatology.

Author information

Author notes

  1. James T. Rosenbaum

    Present address: Corvus Pharmaceuticals, Burlingame, CA, USA

Authors and Affiliations

  1. Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA

    Amr M. Zaki, Eric B. Suhler, Grazyna Adamus & James T. Rosenbaum

  2. Legacy Devers Eye Institute, Portland, OR, USA

    Sirichai Pasadhika & James T. Rosenbaum

  3. Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

    Jerry C. Huang

  4. Tennessee Retina, Nashville, TN, USA

    Akshay S. Thomas

  5. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Bryn M. Burkholder

  6. Centre for Eye Research Australia, University of Melbourne, Parkville, VIC, Australia

    Lyndell L. Lim

  7. Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia

    Lyndell L. Lim

  8. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    Stephanie M. Llop

  9. Portland Veterans Administration Health Care System, Portland, OR, USA

    Eric B. Suhler

  10. Department of Medicine, Oregon Health & Science University, Portland, OR, USA

    James T. Rosenbaum

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Contributions

All authors contributed to the writing, data analysis, and critiquing of the manuscript. All authors contributed patient data except for GA. GA’s laboratory performed the testing for autoantibodies.

Corresponding author

Correspondence to James T. Rosenbaum.

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Competing interests

AST: consultant for Alimera, Allergan, Avesis, Bausch & Lomb, Eyepoint, Genentech, Zeiss. SML: Eyepoint Pharmaceuticals. JTR: consultant for Abbvie, Gilead, Roche, Horizon, Eyevensys, Santen, UCB, Corvus, and Affibody; royalties from UpToDate; clinical trial support from Pfizer and Horizon; and data monitoring for BMS-Celgene and Lilly. The remaining authors declare no competing interests.

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Zaki, A.M., Pasadhika, S., Huang, J.C. et al. Characterization of autoimmune eye disease in association with Down’s syndrome. Eye 38, 386–392 (2024). https://doi.org/10.1038/s41433-023-02706-6

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