Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Nagele, E.P.; Han, M.; Acharya, N.K.; DeMarshall, C.; Kosciuk, M.C.; Nagele, R.G. Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human Sera, and Their Number Is Influenced by Age, Gender, and Disease. PLoS ONE 2013, 8, e60726. [Google Scholar] [CrossRef] [Green Version]
- Plotz, P.H. The Autoantibody Repertoire: Searching for Order. Nat. Rev. Immunol. 2003, 3, 73–78. [Google Scholar] [CrossRef] [PubMed]
- Riemekasten, G.; Petersen, F.; Heidecke, H. What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases. Front. Immunol. 2020, 11, 564526. [Google Scholar] [CrossRef]
- Ardeljan, D.; Chan, C.-C. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging. Prog. Retin. Eye Res. 2013, 37, 68–89. [Google Scholar] [CrossRef] [Green Version]
- Baxter, J.M.; Fotheringham, A.J.; Foss, A.J.E. Determining Patient Preferences in the Management of Neovascular Age-Related Macular Degeneration: A Conjoint Analysis. Eye Lond. Engl. 2016, 30, 698–704. [Google Scholar] [CrossRef] [Green Version]
- Philogene, M.C.; Johnson, T.; Vaught, A.J.; Zakaria, S.; Fedarko, N. Antibodies against Angiotensin II Type 1 and Endothelin A Receptors: Relevance and Pathogenicity. Hum. Immunol. 2019, 80, 561–567. [Google Scholar] [CrossRef]
- Imai, N.; Hashimoto, T.; Kihara, M.; Yoshida, S.; Kawana, I.; Yazawa, T.; Kitamura, H.; Umemura, S. Roles for Host and Tumor Angiotensin II Type 1 Receptor in Tumor Growth and Tumor-Associated Angiogenesis. Lab. Investig. J. Tech. Methods Pathol. 2007, 87, 189–198. [Google Scholar] [CrossRef] [PubMed]
- Banasik, M.; Boratyńska, M.; Kościelska-Kasprzak, K.; Kamińska, D.; Zmonarski, S.; Mazanowska, O.; Krajewska, M.; Bartoszek, D.; Żabińska, M.; Myszka, M.; et al. Non-HLA Antibodies: Angiotensin II Type 1 Receptor (Anti-AT1R) and Endothelin-1 Type A Receptor (Anti-ETAR) Are Associated With Renal Allograft Injury and Graft Loss. Transplant. Proc. 2014, 46, 2618–2621. [Google Scholar] [CrossRef] [PubMed]
- Yin, Y.-J.; Salah, Z.; Maoz, M.; Even Ram, S.C.; Ochayon, S.; Neufeld, G.; Katzav, S.; Bar-Shavit, R. Oncogenic Transformation Induces Tumor Angiogenesis: A Role for PAR1 Activation. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2003, 17, 163–174. [Google Scholar] [CrossRef]
- Duncan, M.B.; Kalluri, R. Parstatin, a Novel Protease-Activated Receptor 1-Derived Inhibitor of Angiogenesis. Mol. Interv. 2009, 9, 168–170. [Google Scholar] [CrossRef] [Green Version]
- Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 2019, 176, 1248–1264. [Google Scholar] [CrossRef] [Green Version]
- Riemekasten, G.; Philippe, A.; Näther, M.; Slowinski, T.; Müller, D.N.; Heidecke, H.; Matucci-Cerinic, M.; Czirják, L.; Lukitsch, I.; Becker, M.; et al. Involvement of Functional Autoantibodies against Vascular Receptors in Systemic Sclerosis. Ann. Rheum. Dis. 2011, 70, 530–536. [Google Scholar] [CrossRef] [PubMed]
- Lim, L.S.; Mitchell, P.; Seddon, J.M.; Holz, F.G.; Wong, T.Y. Age-Related Macular Degeneration. Lancet Lond. Engl. 2012, 379, 1728–1738. [Google Scholar] [CrossRef]
- Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group; Maguire, M.G.; Martin, D.F.; Ying, G.-S.; Jaffe, G.J.; Daniel, E.; Grunwald, J.E.; Toth, C.A.; Ferris, F.L.; Fine, S.L. Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology 2016, 123, 1751–1761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wecker, T.; Ehlken, C.; Bühler, A.; Lange, C.; Agostini, H.; Böhringer, D.; Stahl, A. Five-Year Visual Acuity Outcomes and Injection Patterns in Patients with pro-Re-Nata Treatments for AMD, DME, RVO and Myopic CNV. Br. J. Ophthalmol. 2017, 101, 353–359. [Google Scholar] [CrossRef] [Green Version]
- Adamus, G. Can Innate and Autoimmune Reactivity Forecast Early and Advance Stages of Age-Related Macular Degeneration? Autoimmun. Rev. 2017, 16, 231–236. [Google Scholar] [CrossRef] [Green Version]
- Camelo, S. Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease? Autoimmune Dis. 2014, 2014, 532487. [Google Scholar] [CrossRef] [Green Version]
- Adamus, G.; Chew, E.Y.; Ferris, F.L.; Klein, M.L. Prevalence of Anti-Retinal Autoantibodies in Different Stages of Age-Related Macular Degeneration. BMC Ophthalmol. 2014, 14, 154. [Google Scholar] [CrossRef] [Green Version]
- Morohoshi, K.; Goodwin, A.M.; Ohbayashi, M.; Ono, S.J. Autoimmunity in Retinal Degeneration: Autoimmune Retinopathy and Age-Related Macular Degeneration. J. Autoimmun. 2009, 33, 247–254. [Google Scholar] [CrossRef]
- Morohoshi, K.; Patel, N.; Ohbayashi, M.; Chong, V.; Grossniklaus, H.E.; Bird, A.C.; Ono, S.J. Serum Autoantibody Biomarkers for Age-Related Macular Degeneration and Possible Regulators of Neovascularization. Exp. Mol. Pathol. 2012, 92, 64–73. [Google Scholar] [CrossRef]
- Joachim, S.C.; Bruns, K.; Lackner, K.J.; Pfeiffer, N.; Grus, F.H. Analysis of IgG Antibody Patterns against Retinal Antigens and Antibodies to α-Crystallin, GFAP, and α-Enolase in Sera of Patients with “Wet” Age-Related Macular Degeneration. Graefes Arch. Clin. Exp. Ophthalmol. 2006, 245, 619. [Google Scholar] [CrossRef] [PubMed]
- Umeda, S.; Suzuki, M.T.; Okamoto, H.; Ono, F.; Mizota, A.; Terao, K.; Yoshikawa, Y.; Tanaka, Y.; Iwata, T. Molecular Composition of Drusen and Possible Involvement of Anti-Retinal Autoimmunity in Two Different Forms of Macular Degeneration in Cynomolgus Monkey (Macaca Fascicularis). FASEB J. 2005, 19, 1683–1685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nagai, N.; Oike, Y.; Izumi-Nagai, K.; Koto, T.; Satofuka, S.; Shinoda, H.; Noda, K.; Ozawa, Y.; Inoue, M.; Tsubota, K.; et al. Suppression of Choroidal Neovascularization by Inhibiting Angiotensin-Converting Enzyme: Minimal Role of Bradykinin. Invest. Ophthalmol. Vis. Sci. 2007, 48, 2321–2326. [Google Scholar] [CrossRef] [PubMed]
- Nagai, N.; Oike, Y.; Izumi-Nagai, K.; Urano, T.; Kubota, Y.; Noda, K.; Ozawa, Y.; Inoue, M.; Tsubota, K.; Suda, T.; et al. Angiotensin II Type 1 Receptor-Mediated Inflammation Is Required for Choroidal Neovascularization. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2252–2259. [Google Scholar] [CrossRef] [Green Version]
- Matsuyama, K.; Ogata, N.; Matsuoka, M.; Wada, M.; Takahashi, K.; Nishimura, T. Plasma Levels of Vascular Endothelial Growth Factor and Pigment Epithelium-Derived Factor before and after Intravitreal Injection of Bevacizumab. Br. J. Ophthalmol. 2010, 94, 1215–1218. [Google Scholar] [CrossRef]
- Carneiro, A.M.; Costa, R.; Falcão, M.S.; Barthelmes, D.; Mendonça, L.S.; Fonseca, S.L.; Gonçalves, R.; Gonçalves, C.; Falcão-Reis, F.M.; Soares, R. Vascular Endothelial Growth Factor Plasma Levels before and after Treatment of Neovascular Age-Related Macular Degeneration with Bevacizumab or Ranibizumab. Acta Ophthalmol. Copenh. 2012, 90, e25–e30. [Google Scholar] [CrossRef] [PubMed]
- Zehetner, C.; Kirchmair, R.; Huber, S.; Kralinger, M.T.; Kieselbach, G.F. Plasma Levels of Vascular Endothelial Growth Factor before and after Intravitreal Injection of Bevacizumab, Ranibizumab and Pegaptanib in Patients with Age-Related Macular Degeneration, and in Patients with Diabetic Macular Oedema. Br. J. Ophthalmol. 2013, 97, 454–459. [Google Scholar] [CrossRef]
- Avery, R.L. What Is the Evidence for Systemic Effects of Intravitreal Anti-VEGF Agents, and Should We Be Concerned? Br. J. Ophthalmol. 2014, 98, i7–i10. [Google Scholar] [CrossRef]
n = 164 | |
---|---|
Age (years), mean ± SD | 78.32 ± 8.17 |
gender (m/f) | 63 (38.4%)/101 (61.6%) |
Laterality (OD/OS/OU) | 41 (25.0%), 49 (29.9%), 74(45.1%) |
Study eye (OD/OS) | 84 (51.2%)/80 (49.8%) |
Baseline BCVA (logMar) | 0.34 ± 0.31 |
Baseline CRT (µm) | 346.01 ± 114.81 |
Antibody Level (Units/mL) n = 164 | Standard Deviation | |
---|---|---|
AT1-receptor ab | 8.531 | 10.35 |
PAR1 ab | 3.398 | 7.79 |
VEGF-A ab | 9.262 | 13.96 |
VEGF-B ab | 5.998 | 15.13 |
VEGF-receptor 2 ab | 6.020 | 9.73 |
Mean ± SD | F | R2 | P | |
---|---|---|---|---|
Number of IVIs year 1 | 5.15 ± 2.91 | (5; 109) = 0.671 | 0.30 | 0.646 |
Number of IVIs year 2 | 3.98 ± 2.97 | (5; 88) = 0.473 | 0.26 | 0.795 |
Number of IVIs year 3 | 4.16 ± 3.23 | (5; 67) = 0.384 | 0.28 | 0.858 |
Number of IVIs year 4 | 4.03 ± 3.33 | (5; 59) = 0.436 | 0.77 | 0.436 |
Number of IVIs year 5 | 4.48 ± 3.41 | (5; 52) = 0.402 | 0.04 | 0.845 |
Number of IVIs total | 22.42 ± 12.21 | (5; 53) = 0.611 | 0.05 | 0.692 |
CRT change | −39.06 ± 128.686 | (5; 44) = 0.686 | 0.72 | 0.636 |
BCVA change | 0.345 ± 0.416 | (5; 53) = 0.637 | 0.06 | 0.672 |
Test Statistics | Nagelkerke’s R2 | P | |
---|---|---|---|
SRF development | χ2 (5) = 1.409 | 0.043 | 0.923 |
IRF development | χ2 (5) = 10.268 | 0.234 | 0.068 |
Fibrosis development | χ2 (5) = 4.952 | 0.132 | 0.422 |
Macular bleeding | χ2 (5) = 6.739 | 0.116 | 0.241 |
IVI response 1 year | χ2 (5) = 3.902 | 0.045 | 0.564 |
IVI response 5 years | χ2 (5) = 8.320 | 0.186 | 0.139 |
AT1-Receptor ab | PAR1 ab | VEGF-A ab | VEGF-B ab | VEGF-Receptor 2 ab | Antibody Score | |
---|---|---|---|---|---|---|
IVI response 1 year | 0.443 | 0.522 | 0.416 | 0.418 | 0.435 | 0.430 |
IVI response 5 years | 0.697 | 0.625 | 0.650 | 0.638 | 0.539 | 0.696 |
SRF development | 0.482 | 0.433 | 0.460 | 0.506 | 0.518 | 0.550 |
IRF development | 0.303 | 0.479 | 0.304 | 0.493 | 0.399 | 0.707 |
Fibrosis development | 0.509 | 0.418 | 0.493 | 0.467 | 0.463 | 0.505 |
Macular bleeding | 0.535 | 0.489 | 0.580 | 0.493 | 0.635 | 0.465 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Prasuhn, M.; Hillers, C.; Rommel, F.; Riemekasten, G.; Heidecke, H.; Nassar, K.; Ranjbar, M.; Grisanti, S.; Tura, A. Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years. J. Pers. Med. 2021, 11, 1207. https://doi.org/10.3390/jpm11111207
Prasuhn M, Hillers C, Rommel F, Riemekasten G, Heidecke H, Nassar K, Ranjbar M, Grisanti S, Tura A. Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years. Journal of Personalized Medicine. 2021; 11(11):1207. https://doi.org/10.3390/jpm11111207
Chicago/Turabian StylePrasuhn, Michelle, Caroline Hillers, Felix Rommel, Gabriela Riemekasten, Harald Heidecke, Khaled Nassar, Mahdy Ranjbar, Salvatore Grisanti, and Aysegül Tura. 2021. "Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years" Journal of Personalized Medicine 11, no. 11: 1207. https://doi.org/10.3390/jpm11111207