Koronavirüs hastalığı 2019 ve antinükleer otoantikor oluşumu
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: SARS-CoV-2 virüsünün vücudun öz antijenlerine olan motif benzerliği nedeniyle, hem koronavirüs hastalığı 2019'da (COVID-19) hem de aşılanan kişilerde otoantikor oluşturma olasılığı bulunmaktadır. Bu otoantikorlardan en yaygını anti-nükleer antikorlardır (ANA) ve doku hasarıyla ve olumsuz prognozla ilişkili olabileceği düşünülmektedir. Mevcut tez çalışmasının amacı COVID-19-aşıları/ANA ilişkisini hastalık sonrası seyri, semptom şiddeti ve aşı tiplerinin (konvansiyonel ve mRNA) etkisi gibi parametrelerle kapsamlı olarak incelemek ve ülkemizde COVID-19 ilişkili ANA prevelansını ilk defa ortaya koymaktır. Materyal ve Metot: Çalışma retrospektif olarak tasarlandı ve analizler için her biri farklı bir ANA alt grubunu ölçen üç ayrı ELISA test kiti (anti-dsDNA, anti-ENA ve anti-Hep-2 nükleus testi) geliştirildi. Testlerde kullanılan antijenlerden dsDNA ve ENA buzağı timusundan ekstrakte edilirken, nükleus ise hücre kültür ortamında Hep-2 hücre hattından izole edildi. Geliştirilen kitlerin çok yönlü validasyon analizleri yapıldı ve gerek ticari kitlerle karşılaştırması, gerekse hastalıklarla uyumu yönünden değerlendirildiğinde uluslararası normlara uygun olduğunu belirlendi. Beş farklı deney dizaynıyla; (i) hastalık sonrası ANA oluşum seyri (n= 33, ilk 2 ay, 15 gün arayla), (ii) semptom şiddetinin ANA oluşumuna etkisi (hafif, n=22; şiddetli, n=11), (iii) tek tip aşı uygulamasının (Sinovac, n=57 veya mRNA, n=34) ve (iv) COVID-19 geçirmemiş kişilerde aşı kombinasyonlarının (her iki aşı türünden de bir defa yaptırmak, n=45) ANA pozitifliğe etkisi gibi önemli konular incelendi ve (v) COVID-19 geçirenlerde ANA prevalansı (n=400) belirlendi. Bulgular: COVID- 19 sonrası süreçte ANA oluşum seyri ilk 2 aylık periyotta kümülatif olarak artış gösterirken (p<0.05), semptom şiddeti ile ANA pozitiflik oranı arasında bir ilişki bulunmadı (hafif; % 36,4 - şiddetli; %54.5) (p>0.05). Sinovac aşısının aşılanma sayısına bağlı olarak ANA oranını aşı öncesi döneme göre kümülatif olarak artırdığı görülürken (p<0.05), mRNA aşısının ANA oluşumunu etkilemediği belirlendi (p>0.05). Anti-dsDNA antikoru ise her iki aşının da uygulandığı kişilerde yüksek bulundu (p<0.05). Prevalans çalışmasında COVID-19 geçirmeyen sağlıklı kişilere göre COVID-19 geçirenlerde ANA oranının 2.5 kat arttığı belirlendi (sağlıklı; % 17.5 – COVID-19; % 43.5) (p<0.05). Sonuç: COVID-19 geçiren her iki-üç kişiden birinde ANA'nın pozitif olduğu görülmüş ve aşı içeriğinde bulunan viral partiküllerin ANA oluşumunu tetiklediği belirlenmiştir. Elde edilen tüm bulgular birlikte değerlendirildiğinde, SARS-CoV-2'nin otoimmün bir virüs olduğu ve immün reaksiyonları tetikleyebileceği sonucuna varılmıştır. Anahtar Kelimeler: COVID-19, koronavirüs aşısı, antinükleer otoantikor, ANA
Aim: Due to the motif similarity of the SARS-CoV-2 virus to the body's self-antigens, there is a possibility of producing autoantibodies in both coronavirus disease 2019 (COVID-19) and vaccinated individuals. Anti-nuclear antibodies (ANA), the most common of these autoantibodies, are thought to be associated with tissue damage and poor prognosis. The aim of the current thesis study is to comprehensively examine the COVID-19-vaccines/ANA relationship with parameters such as post-disease course, symptom severity and the effect of vaccine types (conventional and mRNA) and to reveal the prevalence of COVID-19-related ANA in our country for the first time. Meterial and Method: The study was designed retrospectively and three separate ELISA test kits (anti-dsDNA, anti-ENA and anti-Hep-2 nucleus test) were developed for the analyses, each measuring a different ANA subgroup. Among the antigens used in the tests, dsDNA and ENA were extracted from calf thymus, and the nucleus was isolated from the Hep-2 cell line in cell culture. Multifaceted validation analyzes of the developed kits were performed, and when evaluated in terms of both comparison with commercial kits and compatibility with diseases, it was determined that they were in compliance with international norms. With five different experimental designs; (i) course of ANA formation after the disease (n = 33, first 2 months, 15 days apart), (ii) effect of symptom severity on ANA formation (mild, n = 22; severe, n = 11), (iii) single type of vaccine administration (Sinovac, n=57 or mRNA, n=34) and (iv) vaccine combinations (receiving both types of vaccines once, n=45) on ANA positivity in people who have not had COVID-19 were examined and (v) the prevalence of ANA (n=400) was determined in those who had COVID-19. Results: In the post-COVID-19 period, the course of ANA formation increased cumulatively in the first 2-month period (p<0.05) and there was no relationship between symptom severity and ANA positivity rate (mild; 36.4% - severe; 54.5%) (p>0.05) . It was determined that the Sinovac vaccine cumulatively increased the rate of ANA depending on the number of vaccinations compared to the pre-vaccine period (p<0.05), but the mRNA vaccine did not affect the formation of ANA (p>0.05). Anti-dsDNA antibody was found to be high in people who received both vaccines (p<0.05). In the prevalence study, it was determined that the ANA rate increased 2.5 times in those who had COVID-19 compared to healthy people who did not have COVID-19 (healthy; 17.5% – COVID-19; 43.5%) (p<0.05). Conclusion: It has been observed that one in every two-three people with COVID-19 is positive for ANA, and it has been determined that the viral particles contained in the vaccine trigger the formation of ANA. When all the findings were evaluated together, it was concluded that SARS-CoV-2 is an autoimmune virus and can trigger immune reactions. Keywords: COVID-19, coronavirus vaccine, antinuclear autoantibody, ANA
Aim: Due to the motif similarity of the SARS-CoV-2 virus to the body's self-antigens, there is a possibility of producing autoantibodies in both coronavirus disease 2019 (COVID-19) and vaccinated individuals. Anti-nuclear antibodies (ANA), the most common of these autoantibodies, are thought to be associated with tissue damage and poor prognosis. The aim of the current thesis study is to comprehensively examine the COVID-19-vaccines/ANA relationship with parameters such as post-disease course, symptom severity and the effect of vaccine types (conventional and mRNA) and to reveal the prevalence of COVID-19-related ANA in our country for the first time. Meterial and Method: The study was designed retrospectively and three separate ELISA test kits (anti-dsDNA, anti-ENA and anti-Hep-2 nucleus test) were developed for the analyses, each measuring a different ANA subgroup. Among the antigens used in the tests, dsDNA and ENA were extracted from calf thymus, and the nucleus was isolated from the Hep-2 cell line in cell culture. Multifaceted validation analyzes of the developed kits were performed, and when evaluated in terms of both comparison with commercial kits and compatibility with diseases, it was determined that they were in compliance with international norms. With five different experimental designs; (i) course of ANA formation after the disease (n = 33, first 2 months, 15 days apart), (ii) effect of symptom severity on ANA formation (mild, n = 22; severe, n = 11), (iii) single type of vaccine administration (Sinovac, n=57 or mRNA, n=34) and (iv) vaccine combinations (receiving both types of vaccines once, n=45) on ANA positivity in people who have not had COVID-19 were examined and (v) the prevalence of ANA (n=400) was determined in those who had COVID-19. Results: In the post-COVID-19 period, the course of ANA formation increased cumulatively in the first 2-month period (p<0.05) and there was no relationship between symptom severity and ANA positivity rate (mild; 36.4% - severe; 54.5%) (p>0.05) . It was determined that the Sinovac vaccine cumulatively increased the rate of ANA depending on the number of vaccinations compared to the pre-vaccine period (p<0.05), but the mRNA vaccine did not affect the formation of ANA (p>0.05). Anti-dsDNA antibody was found to be high in people who received both vaccines (p<0.05). In the prevalence study, it was determined that the ANA rate increased 2.5 times in those who had COVID-19 compared to healthy people who did not have COVID-19 (healthy; 17.5% – COVID-19; 43.5%) (p<0.05). Conclusion: It has been observed that one in every two-three people with COVID-19 is positive for ANA, and it has been determined that the viral particles contained in the vaccine trigger the formation of ANA. When all the findings were evaluated together, it was concluded that SARS-CoV-2 is an autoimmune virus and can trigger immune reactions. Keywords: COVID-19, coronavirus vaccine, antinuclear autoantibody, ANA
Açıklama
Sağlık Bilimleri Enstitüsü, Fizyoloji Ana Bilim Dalı
Anahtar Kelimeler
Fizyoloji, Physiology
