Detection of autoantibodies specific for inflammation-associated proteins in COVID-19 patients

master's thesis

• Title (croatian): Detekcija autoantitijela specifičnih za proteine upale kod oboljelih od bolesti COVID-19
• Author: Marija Lugar
• Mentor: Ezio Bonifacio (mentor)
• Mentor: Petra Korać (sumentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Zorana Grubić (član povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Coronavirus disease 2019 (COVID-19) manifests a variety of symptoms: from being asymptomatic or
mild in most of the infected individuals, to causing more severe and even life-threatening conditions in
about 20% of the patients. As an effector of the immune system and a hallmark of autoimmunity,
autoantibodies are hypothesized to play a role in the pathogenesis of COVID-19 and pose a risk for a
severe disease outcome. Hence, this thesis aimed to detect and investigate the prevalence of
autoantibodies in sera from COVID-19 patients. Thereby, 100 hospitalized COVID-19 patients of
different disease severity (42 moderate and 58 severe/critical) and 41 SARS-CoV-2 seronegative
healthy blood donors were tested for autoantibodies specific for different inflammation-associated
proteins (interferon (IFN), complement, and DDX helicases) by the luciferase immunoprecipitation
system (LIPS) assay. The results show a high prevalence of autoantibodies measured in hospitalized
COVID-19 patients (51%) in contrast to the control group (12.2%). However, only 8% of the patients
had high and/or intermediate titers (IFN autoantibodies), whereas, in the remaining autoantibodypositive patients only low autoantibody titers were detected. Autoantibodies specific for complement
proteins and DDX helicases were detected only in low titers. Interestingly, contrary to previous reports,
no association with disease severity, sex, or age was observed for IFN autoantibodies. Overall, the
findings suggest that from the measured autoantibodies, IFN autoantibodies could be a relevant
prognostic marker in COVID-19, specifically for COVID-19 patients that require hospitalization. The
findings emphasize the importance of a wider investigation of autoantibodies in COVID-19.

Abstract (croatian)

Bolest COVID-19 (od eng. coronavirus disease 2019) uključuje širok spektar simptoma: većina
zaraženih pojedinaca nemaju simptome ili imaju blage simptome, dok se kod otprilike 20% slučajeva
manifestira teški ili kritični oblik bolesti. Pretpostavlja se da autoantitijela, kao jedan od aktera
imunosnog sustava te obilježje autoimunih bolesti, imaju ulogu u patogenezi bolesti COVID-19 te da
predstavljaju rizik za razvoj težeg oblika bolesti. Glavni cilj ovog rada bio je detektirati autoantitijela
kod bolesnika obljelih od bolesti COVID-19. Kako bi se ispitala prisutnost autoantitijela specifičnih za
proteine upale (interferona (IFN), proteina komplementa te helikaze DEAD-box), uzorci 100 bolesnika
obljelih od bolesti COVID-19, od toga 42 s umjerenim i 58 s težim/kritičnim oblikom bolesti, te 41
uzorak SARS-CoV-2 seronegativnih zdravih donora krvi testirani su na autoantitijela
imunoprecipitacijskim testom luciferaze (LIPS, od eng. luciferaze immunoprecipitation system).
Rezultati ukazuju na visoku prevalenciju autoantitijela kod hospitaliziranih bolesnika obljelih od bolesti
COVID-19 (51%) u odnosu na kontrolnu skupinu (12.2%). Međutim, tek 8% pacijenata imalo je srednji
ili visoki titar autoantitijela, isključivo specifičnih za IFN, dok je kod ostalih pacijenata pozitivnih na
autoantitijela uočen tek nizak titar autoantitijela. Autoantitijela specifična za ostale testirane antigene
sustava komplementa i helikaza DEAD-box detektirana su u vrlo niskom titru. Zanimljivo je da
suprotno rezultatima prijašnjih studija, u ovom radu nije uočena povezanost IFN autoantitijela s dobi,
spolom ili težinom bolesti. Rezultati ukazuju da od testiranih autoantitijela, jedino ona specifična za
interferone mogu biti potencijalni marker bolesti COVID-19, posebice za hospitalizirane pacijente. Ovi
rezultati pridodaju važnosti šireg istraživanja autoantitijela kod oboljelih od bolesti COVID-19.

• Keywords: SARS-CoV-2; complement proteins; DEAD-box helicases; cytokines; cross-reactivity; molecular mimicry; LIPS assay
• Keywords (croatian): SARS-CoV-2; proteini komplementa; helikaze DEAD-box; citokini; krosreaktivnost; molekularna mimikrija; LIPS esej
• Language: english
• URN:NBN: urn:nbn:hr:217:579521
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-09-21
• Created on: 2022-10-25 11:44:46