Features of IgG-antibodies production to individual Cytomegalovirus proteins in various eye diseases (age-related macular degeneration and central serous chorioretinopathy)

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Abstract

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are diseases targeting the posterior segment of the eye that often lead to lowered visual functions. Pathogenesis of such disorders largely remains unclear. Among the risk factors of developing chronic inflammation, various microorganisms are considered, particularly Cytomegalovirus (CMV ). The study was aimed at analyzing the humoral response to individual viral proteins during chronic and reactivated CMV infection in AMD and CSC patients. Materials and methods. 104 CMV-seropositive patients were enrolled in the study including 75 AMD and 29 CSC subjects. IgM- and IgG-antibodies specific to CMV late viral antigens as well as IgG antibodies against the main non-structural immediate early (IE) antigen were evaluated by ELISA. IgG antibodies to individual CMV phosphoproteins such as the main non-structural immediate early protein (IE), the DNA-binding phosphoprotein pp52, and the tegument phosphoproteins (pp150, pp65, and pp28) were assessed by using Line-Immunoassay: recombinant antigens containing immunodominant protein fragments derived from viral antigens (p52, p150, p65, p28) were used. Positive (bands 2+) and strongly positive (bands 3+) data were only used for analysis. Results. It was shown that in both groups patients with chronic CMV infection had comparable rate of detected antibodies specific to individual antigens. The level of seropositivity to CMV р150 and р65 was significantly higher than that to CMV р52 and р28 (p < 0.05). Patients with AMD compared to patients with CSС had significantly higher moderate positive response (2+) to all the antigens examined. Upon reactivation of chronic CMV infection in AMD patients, the level of seropositivity to all antigens was increased, the number of cases with an intensely positive response to individual antigens was elevated, but patients with moderate positive response still prevailed. However, reactivation of chronic CMV infection was observed only in 6 CSС patients, allowing to perform no comparative analysis between these two groups. Conclusion. The main difference between CMV-chronically infected patients with AMD and CSC was not found at the level of seropositivity to individual CMV recombinant antigens, but rather in magnitude of antibody production so that AMD patients in comparison to CSC patients displayed moderate antibody production (bands 2+). A marked difference was related to the level of antibodies against CMV p150: AMD patients showed moderate antibody response (bands 2+), whereas CSC subjects dominated with strong positive response (bands 3+) (p < 0.05). It seems that moderate antibody production to recombinant CMV antigens examined in AMD patients occurs due to a weak expression of such viral antigens during chronic infection, resulting in long-term maintenance of antigenic stimulation leading to prolonged inflammation.

About the authors

V. V. Neroev

Helmholtz National Medical Research Center of Eye Diseases

Email: sekr@igb.ru
ORCID iD: 0000-0002-8480-0894

RAS Full Member, PhD, MD (Medicine), Director of the Helmholtz National Medical Research Center of Eye Diseases.

Moscow.

Russian Federation

G. I. Krichevskaya

Helmholtz National Medical Research Center of Eye Diseases

Author for correspondence.
Email: gkri@yandex.ru
ORCID iD: 0000-0001-7052-3294

Galina I. Krichevskaya - PhD (Medicine), Leading Researcher, Department of Immunology and Virology, Helmholtz National Medical Research Center of Eye Diseases.

105062, Moscow, Sadovaya-  Chernogryazskaya str., 14/19.

Phone: +7 (495) 624-57-13 (office), +7 985 191-92-34 (mobile)

Russian Federation

G. I. Alatortseva

I.I. Mechnikov Research Institute for Vaccines and Sera

Email: gkri@yandex.ru
ORCID iD: 0000-0001-9887-4061

PhD (Biology), Head of the Laboratory for Cloning Viral Genomes, I.I. Mechnikov Research Institute for Vaccines and Sera.

Moscow.

Russian Federation

M. V. Ryabina

Helmholtz National Medical Research Center of Eye Diseases

Email: mryabina@yandex.ru
ORCID iD: 0000-0001-7961-8695

PhD (Medicine), Senior Researcher, Department of Retinal and Optic Nerve Pathology, Helmholtz National Medical Research Center of Eye Diseases.

Moscow.

Russian Federation

A. P. Sarygina

Helmholtz National Medical Research Center of Eye Diseases

Email: _anna_84@mail.ru
ORCID iD: 0000-0002-2471-1769

Junior Researcher, Department of Retinal and Optic Nerve Pathology, Helmholtz National Medical Research Center of Eye Diseases.

Moscow.

Russian Federation

L. N. Nesterenko

I.I. Mechnikov Research Institute for Vaccines and Sera

Email: gkri@yandex.ru
ORCID iD: 0000-0002-3825-3906

PhD (Chemistry), Leading Researcher, Laboratory for Cloning Viral Genomes, I.I. Mechnikov Research Institute for Vaccines and Sera.

Moscow.

Russian Federation

V. V. Dotsenko

I.I. Mechnikov Research Institute for Vaccines and Sera

Email: gkri@yandex.ru

PhD (Biology), Senior Researcher, Laboratory for Cloning Viral Genomes, I.I. Mechnikov Research Institute for Vaccines and Sera.

Moscow.

Russian Federation

L. N, Luhverchik

I.I. Mechnikov Research Institute for Vaccines and Sera

Email: gkri@yandex.ru
ORCID iD: 0000-0002-2997-8892

PhD (Biology), Leading Researcher, Laboratory for Cloning Viral Genomes, I.I. Mechnikov Research Institute for Vaccines and Sera.

Moscow.

Russian Federation

References

  1. Алексеев И.Б., Нам Ю.А., Непесова О.М. Патогенетические особенности развития дистрофических процессов сетчатки при миопии и возрастной макулярной дегенерации // Российский офтальмологический журнал. 2017. Т. 10, № 4. С. 90—96.
  2. Игнатьев С.А., Алексеев И.Б., Чернакова Г.М., Клещева Е.А., Нам Ю.А. Возрастная макулярная дегенерация и цитомегаловирус: дискуссионные аспекты патогенеза // Российский офтальмологический журнал. 2015. Т. 8, № 4. С. 71-78.
  3. Марданлы С.С., Арсеньева В.А., Захаров М.В., Марданлы С.Г., Амелина Е.А., Ротанов С.В. Применение линейного иммуноблоттинга для скрининга антител класса и М к основным возбудителям TORCH-инфекций // Эпидемиология и вакцинопрофилактика. 2015. Т. 3, № 82. С. 59-65.
  4. Мирзабекова К.А. Центральная серозная хориоретинопатия — современные подходы к лечению // Вестник офтальмологии. 2012. № 6. С. 62-64.
  5. Мухамедьянова А.Ш., Азнабаев Р.А., Азнабаева Л.Ф. Клинические и иммунологические факторы возникновения и течения возрастной макулярной дегенерации // Вестник офтальмологии. 2014. Т. 130, № 3. С. 9-12.
  6. Нероев В.В. Российское наблюдательное эпидемиологическое неинвертеционное исследование пациентов с влажной формой макулярной дегенерации // Российский офтальмологический журнал. 2011. Т 4, № 2. С. 4-9.
  7. Нероев В.В., Рябина М.В., Цапенко И.В., Зуева М.В., Чиковани К.Р. Клинико-функциональные особенности различных форм центральной серозной хориоретинопатии // Российский офтальмологический журнал. 2011. Т. 4, № 1. С. 52-57.
  8. Нероев В.В., Цапенко И.В., Зуева М.В., Рябина М.В., Чиковани К.Р. Морфофункциональные изменения сетчатки и ретинального пигментного эпителия у больных центральной серозной хориоретинопатией на фоне длительной системной стероидной терапии // Российский офтальмологический журнал. 2012. Т. 5, № 3. С. 34-38.
  9. Никитина А.В., Помелова В.Г., Соколова М.В., Осин Н.С., Марданлы С.Г. Выбор антигенов для определения иммуноглобулина G к цитомегаловирусу на основе технологии ФОСФАН // Клиническая лабораторная диагностика. 2015. Т. 60, № 10. С. 36-39.
  10. Слепова О.С., Еремеева Е.А., Рябина М.В., Сорожкина Е.С. Роль инфекции в патогенезе возрастной макулярной дегенерации // Вестник офтальмологии. 2015. Т. 131, № 4. С. 56—59. doi: 10.17116/oftalma2015131456-59
  11. Biolatti М., Dell'Oste V., De Andrea М., Landolfo S. The human cytomegalovirus tegument protein pp65(pUL83): a key player in innate immune evasion. New Microbiologica, 2018, vol. 41, no. 2, pp. 87—94.
  12. Kalejta R.F. Tegument proteins of human cytomegalovirus. Microbiol. Mol. Biol. Rev., 2008, vol. 72, no. 2, pp. 249—265. doi: 10.1128/VVBR.00040-07
  13. Miller D.M., Espinosa-Heidmann D.G., Legra J., Dubovy S.R., Suner I.J., Sedmak D.D., Dix R.D., Cousins S.W. The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am. J. Ophthalmol., 2004, vol. 138, no. 3,pp. 323-28. doi: 10.1016/j.ajo.2004.03.018
  14. Nulens E., Bodeus M., Bonelli F., Soleti A., Goubau P. Reactivity to p52 and CM2 recombinant proteins in primary human cytomegalovirus infection with a microparticle agglutination assay. Clin. Diagn. Lab. Immunol., 2000, vol. 7, no. 4, pp. 536-539. doi: 10.1128/cdli.7.4.536-539.2000
  15. Pepperl S., Munster J., Mach M., Harris J.R., Plachter B. Dense bodies of human cytomegalovirus induce both humoral and cellular immune responses in the absence of viral gene expression. J. Virol., 2000, vol. 74, no. 13, pp. 6132- 6146. doi: 10.1128/jvi.74.13.6132-6146.2000
  16. Smith R.M., Kosuri S., Kerry J.A. Role of human cytomegalovirus tegument proteins in virion assembly. Viruses, 2014, vol. 6, no. 2, pp. 582-605. doi: 10.3390/v6020582
  17. Tomtishen J.P. 3rd. Human cytomegalovirus tegument proteins (pp65, pp71, pp150, pp28). Virol. J., 2012, vol. 9: 22. doi: 10.1186/1743-422X-9-22
  18. Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J., Pasa-Tolic L., Wang D., Camp D.G. 2nd, Rodland K., Wiley S., Britt W., Shenk T., Smith R.D., Nelson J.A. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J. Virol., 2004, vol. 78, no. 20, pp. 10960-10966. doi: 10.1128/JVI.78.20.10960-10966.2004

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Copyright (c) 2020 Neroev V.V., Krichevskaya G.I., Alatortseva G.I., Ryabina M.V., Sarygina A.P., Nesterenko L.N., Dotsenko V.V., Luhverchik L.N.

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