Skip to main content

Advertisement

SpringerLink
Log in

Serum antiretinal antibodies and cytokine profiling in autoimmune retinopathy and their association with clinical outcomes

  • Inflammatory Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Autoimmune retinopathy (AIR) is a group of autoimmune retinal diseases that can cause blindness. The purpose of this study is to investigate the profiles of serum antiretinal antibodies (ARAs) and cytokines and their association with disease diagnosis as well as clinical features in AIR.

Methods

The patients with presumed para (p) and non-paraneoplastic (np) AIR diagnosis, the patients with retinitis pigmentosa and bilateral uveitis as disease controls, and healthy subjects were prospectively enrolled. Western blotting and Luminex multiple cytokine assay/enzyme linked immunosorbent assay were used to determine the presence of serum ARAs and the concentration of cytokines, respectively. Kruskal–Wallis or chi square test was applied to compare the profiles of ARA and cytokines among various groups. The multilevel mixed-effect regression was used to investigate the association of ARA or cytokines with clinical features.

Results

No significant difference in the band number and subtypes of serum ARAs was found between AIR patients and their controls. AIR patients had higher concentration of serum IFN-ɤ, CXCL9, or CXCL10 than non-AIR controls. A positive correlation was found between increased number of ARAs and elevated TNF-α in np-AIR patients. Elevated pro-inflammatory cytokines or ARA subtypes (antibody against recoverin and α-enolase) were associated with worse retinal functions or anatomy, including visual acuity, visual field, ERG parameters, and central retinal thickness.

Conclusions

The data of our study demonstrate that detection of serum ARAs has limited value in the diagnosis of AIR. Th1-type cytokines/chemokines or specific ARA subtypes are associated with pathogenesis and disease severity of the AIR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Grange L, Dalal M, Nussenblatt RB, Sen HN (2014) Autoimmune retinopathy. Am J Ophthalmol 157:266–272

    Article  CAS  PubMed  Google Scholar 

  2. Rahimy E, Sarraf D (2013) Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: evaluation and management. Surv Ophthalmol 58:430–458

    Article  PubMed  Google Scholar 

  3. Kyger M, Worley A, Adamus G (2013) Autoimmune responses against photoreceptor antigens during retinal degeneration and their role in macrophage recruitment into retinas of RCS rats. J Neuroimmunol 254:91–100

    Article  CAS  PubMed  Google Scholar 

  4. Adamus G (2018) Are anti-retinal autoantibodies a cause or a consequence of retinal degeneration in autoimmune retinopathies? Front Immunol 9:765

    Article  PubMed  PubMed Central  Google Scholar 

  5. Grewal DS, Fishman GA, Jampol LM (2014) Autoimmune retinopathy and antiretinal antibodies: a review. Retina 34:827–845

    Article  CAS  PubMed  Google Scholar 

  6. Fox AR, Gordon LK, Heckenlively JR et al (2016) Consensus on the diagnosis and management of nonparaneoplastic autoimmune retinopathy using a modified Delphi approach. Am J Ophthalmol 168:183–190

    Article  PubMed  PubMed Central  Google Scholar 

  7. Heckenlively JR, Aptsiauri N, Nusinowitz S et al (1996) Investigations of antiretinal antibodies in pigmentary retinopathy and other retinal degenerations. Trans Am Ophthalmol Soc 94:179–200 (discussion 200-206)

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Shimazaki K, Jirawuthiworavong GV, Heckenlively JR, Gordon LK (2008) Frequency of anti-retinal antibodies in normal human serum. J Neuro-Ophthalmol 28:5–11

    Article  Google Scholar 

  9. Zeng H, Liu Q, Peng X et al (2019) Detection of serum anti-retinal antibodies in the Chinese patients with presumed autoimmune retinopathy. Graefes Arch Clin Exp Ophthalmol 257:1759–1764

    Article  CAS  PubMed  Google Scholar 

  10. Dutta Majumder P, Marchese A, Pichi F et al (2020) An update on autoimmune retinopathy. Indian J Ophthalmol 68:1829

    Article  PubMed  PubMed Central  Google Scholar 

  11. Davoudi S, Ebrahimiadib N, Yasa C et al (2017) Outcomes in autoimmune retinopathy patients treated with rituximab. Am J Ophthalmol 180:124–132

    Article  CAS  PubMed  Google Scholar 

  12. Armbrust K, Fox A, Jeffrey B et al (2021) Rituximab for autoimmune retinopathy: results of a phase I/II clinical trial. Taiwan J Ophthalmol 11:64

    Article  PubMed  Google Scholar 

  13. Stanwyck LK, Chan W, Sood A et al (2020) Correlation of immunological markers with disease and clinical outcome measures in patients with autoimmune retinopathy. Trans Vis Sci Tech 9:15

    Article  Google Scholar 

  14. Lundy SK, Nikoopour E, Karoukis AJ et al (2018) T helper 1 cellular immunity toward recoverin is enhanced in patients with active autoimmune retinopathy. Front Med 5:249

    Article  Google Scholar 

  15. Detrick B, Gangaputra S, Palsgrove DN et al (2018) Elevated serum levels of IL-6 and CXCL9 in autoimmune retinopathy (AIR) patients. J Neuroimmunol 316:74–79

    Article  CAS  PubMed  Google Scholar 

  16. Stansky E, Biancotto A, Dagur PK et al (2017) B cell anomalies in autoimmune retinopathy (AIR). Invest Ophthalmol Vis Sci 58:3600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Saito M, Saito W, Kanda A et al (2014) A case of paraneoplastic optic neuropathy and outer retinitis positive for autoantibodies against collapsin response mediator protein-5, recoverin, and α-enolase. BMC Ophthalmol 14:5

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32:2847–2849

    Article  CAS  PubMed  Google Scholar 

  19. Adamus G, Champaigne R, Yang S (2020) Occurrence of major anti-retinal autoantibodies associated with paraneoplastic autoimmune retinopathy. Clin Immunol 210:108317

    Article  CAS  PubMed  Google Scholar 

  20. Chen JJ, McKeon A, Greenwood TM et al (2021) Clinical utility of antiretinal antibody testing. JAMA Ophthalmol 139:658

    Article  PubMed  Google Scholar 

  21. Forooghian F (2015) The uncertainty regarding antiretinal antibodies. JAMA Ophthalmol 133:744–745

    Article  PubMed  Google Scholar 

  22. Stanwyck LK, Moussa K, Chan W et al (2019) Lack of correlation between number of antiretinal antibodies and clinical outcome measures in autoimmune retinopathy patients. Ophthalmol Retina 3:1007–1009

    Article  PubMed  Google Scholar 

  23. Shekhawat J, Gauba K, Gupta S et al (2021) Interleukin-6 perpetrator of the COVID-19 cytokine storm. Ind J Clin Biochem 36:440–450

    Article  CAS  Google Scholar 

  24. Weinstein Jessica E, Pepple KL (2018) Cytokines in uveitis. Curr Opin Ophthalmol 29:267–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Balamurugan S, Das D, Hasanreisoglu M et al (2020) Interleukins and cytokine biomarkers in uveitis. Ind J Ophthalmol 68:1750–1763

    Article  CAS  Google Scholar 

  26. Ohno S (1981) Immunological aspects of Behçet’s and Vogt-Koyanagi-Harada’s diseases. T Ophthal Soc UK 101:335–41

    Google Scholar 

  27. Deaner JD, Jaffe GJ, Keenan RT et al (2022) Anti–interleukin-6 antibodies for autoimmune retinopathy with macular edema. Ophthalmology Retina 6:91–93

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by Beijing Municipal Natural Science Foundation (7192034, H.Y.Z, 7202079, Q.G.), Key Research Program of Beijing Institute of Ophthalmology 2019–2020 (H.Y.Z.), the National Key Research and Development Program of China (2017YFA0104500, Q.G.) and National Natural Science Foundation of China (32070897, 31671244, Q.G.).

Author information

Author notes

  1. Hui-yang Zeng and Qing Ge are co-corresponding authors.

Authors and Affiliations

  1. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Hui-Yang Zeng, Qian Liu, Kai Cao, Ning-li Wang & Zi-jun Zhang

  2. Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China

    Hui-Yang Zeng, Qian Liu, Kai Cao, Ning-li Wang & Zi-jun Zhang

  3. Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China

    Yujia Wang & Qing Ge

  4. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Beijing, 100191, China

    Qing Ge

Authors
  1. Hui-Yang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kai Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ning-li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yujia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zi-jun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qing Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hui-Yang Zeng or Qing Ge.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Beijing Tongren Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, HY., Liu, Q., Cao, K. et al. Serum antiretinal antibodies and cytokine profiling in autoimmune retinopathy and their association with clinical outcomes. Graefes Arch Clin Exp Ophthalmol 261, 2651–2660 (2023). https://doi.org/10.1007/s00417-023-06081-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-023-06081-6

Keywords

Search

Navigation