Naslov (srp)

Značaj dokazivanja anti-Epštajn Bar virusnih antitela u pacijenata sa sistemskim eritemskim lupusom: : udruženost sa kliničkim i imunoserološkim ispoljavanjem bolesti : doktorska disertacija

Autor

Mišković, Rada, 1980-

Doprinosi

Rašković, Sanvila, 1959-
Miljanović, Danijela, 1984-
Perić-Popadić, Aleksandra, 1961-
Banko, Ana, 1982-
Tomić-Spirić, Vesna, 1963-

Opis (srp)

Uvod: Sistemski eritemski lupus (SEL) je multisistemsko autoimuno oboljenje heterogenekliničke prezentacije, koje prevashodno zahvata osobe ženskog pola, najčešće u reproduktivnomperiodu. Nastaje u kompleksnoj interreakciji genetičke osnove i faktora sredine, među kojimainfektivni agensi, posebno Epštajn-Bar virus (EBV) imaju značajnu ulogu.Ciljevi istraživanja: Ciljevi ovog istraživanja su ispitati serološke i molekularne markere istatus EBV infekcije u ispitanika sa SEL u odnosu na kontrolnu grupu, utvrditi njihovu udruženostsa stepenom aktivnosti, kliničkim i imunoserološkim manifestacijama bolesti, promenu markera istatusa EBV infekcije u ispitanika sa aktivnim SEL nakon šest meseci u odnosu na postizanjeremisije/stanja niske aktivnosti SEL, identifikovati prediktore prelaska iz aktivne u latentnu EBVinfekciju i analizirati genetičke faktore koji bi mogli uticati na odgovor organizma na EBVinfekciju i način ispoljavanja SEL.Materijal i metodologija: Sprovedena je prospektivna kohortna studija koja je obuhvatila103 ispitanika sa dijagnozom SEL koji su lečeni na Klinici za alergologiju i imunologijuUniverzitetskog kliničkog centra Srbije. Ispitanici sa aktivnim SEL (klinički SLEDAI ≥4 i ukupniSLEDAI≥6) su praćeni tokom šest meseci, nakon čega je učinjena nova procena aktivnosti bolesti ianaliza markera EBV infekcije. Primarni ishod u ovoj grupi ispitanika bio je postizanje remisije iliniske aktivnosti lupusa (eng. Lupus Low Disease Activity, LLDAS) nakon šest meseci praćenja.Kontrolnu grupu činilo je 99 ispitanika starijih od 18. godina, koji nisu imali dijagnozu sistemskeautoimunske ili aktivne maligne bolesti, niti pozitivnu porodičnu anamnezu za iste. Određivanasu antitela na EBV antigene EBNA 1 (IgG), VCA (IgM, IgG) i EA(D) (IgM, IgG) u uzorcima serumaprimenom komercijalnih ELISA testova prema uputstvima proizvođača. Aktivna EBV infekcija jedefinisana prisustvom virusne DNK (pozitivna EBNA1 i/ili LMP1) i/ili prisustvom anti-VCA IgMi/ili anti-EA(D) IgM antitela. Komercijalni TaqMan SNP esej je korišćen za određivanje genotipovaIL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, rs9610), IL10RB(rs999788, rs2834167, rs1058867) i IL22RA (rs16829204, rs3795299). Aktivnost bolestiprocenjivana je primenom sledećih skala i skorova: SLEDAI 2K, LFA-REAL ClinRO i PGA.SLICC/ACR Damage Index je korišćen za procenu akumuliranog oštećenja. Od pacijenata jetraženo da daju svoju procenu aktivnosti bolesti primenom LFA REAL PRO, a stepen zamoraocenjivan je primenom FACIT-F skale.Rezultati: Ispitivanjem je obuhvaćeno 103 ispitanika sa SEL, većinom žena (91,3%),prosečne starosti 45,42±12,9 godina. Limfopenija (50%), alopecija (39%), artritis (32%) ileukopenija (32%) bile su najčešće kliničke manifestacije. Aktivna forma bolesti bila je prisutnakod 51 (49,5%) ispitanika. Kontrolnu grupu činilo je 99 ispitanika, većinom žena (88%), prosečnestarosti 55,43±13,62 godine. Aktivna EBV infekcija je značajno češće bila prisutna u ispitanika saSEL (41,7%) u odnosu na kontrolnu grupu (9,2%). Ispitanici sa SEL imali su višu prevalencu ititar anti-VCA IgM, anti-EA(D) IgG i anti-EA(D) IgM antitela u odnosu na kontrolnu grupu(p<0,001, p<0,001, p=0,008, redom)...

Opis (srp)

Medicina - Zapaljenje i autoimunost / Medicine- Inflammation and autoimmunity Datum odbrane: 25.09.2023.

Opis (eng)

ntroduction: Systemic lupus erythematosus (SLE) is a multisystemic autoimmunedisease with a heterogeneous clinical presentation, which primarily affects women in thereproductive period. It develops in a complex interaction of genetic and environmental factors,among which infectious agents, especially the Epstein-Barr virus (EBV), play a significant role.Aims: The aims of this research were to examine serological and molecular markers andthe status of EBV infection in subjects with SLE compared to the control group, to investigatetheir association with the disease activity, clinical and immunoserological SLE manifestations,changes in the markers and status of EBV infection in subjects with active SLE after six months inrelation to the achievement of remission/state of low lupus activity, identify predictors oftransition from active to latent EBV infection and analyze genetic factors that could affect theresponse to EBV infection and the SLE manifestations.Materials and methods: A prospective cohort study was conducted that included 103subjects with SLE who were treated at the Clinic for Allergy and Immunology University ClinicalCenter of Serbia. Subjects with active SLE (clinical SLEDAI ≥4 and total SLEDAI≥6) were followedfor six months, after which a new assessment of disease activity and analysis of markers of EBVinfection was performed. The primary outcome was the achievement of remission or low lupusactivity (Lupus Low Disease Activity, LLDAS) after six months of follow-up. The control groupconsisted of 99 subjects ≥18 yeras, without the diagnosis of systemic autoimmune or activemalignant disease, nor a positive family history. Antibodies to EBV antigens EBNA 1 (IgG), VCA(IgM, IgG), and EA(D) (IgM, IgG) were determined in serum samples using commercial ELISAtests according to the manufacturer's instructions. Active EBV infection was defined by thepresence of viral DNA (positive EBNA1 and/or LMP1) and/or the presence of anti-VCA IgMand/or anti-EA(D) IgM antibodies. A commercial TaqMan SNP assay was used to determine thegenotypes of IL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, rs9610),IL10RB (rs999788, rs2834167, rs1058867) and IL22RA (rs168292). 04, rs3795299). Diseaseactivity was assessed using the following scales: SLEDAI 2K, LFA-REAL ClinRO and PGA. TheSLICC/ACR Damage Index was used to assess accumulated damage. Patients were asked to assessSLE activity using LFA REAL PRO, and the degree of fatigue was assessed using the FACIT-F scale.Results: The study included 103 SLE patients, mostly women (91.3%), average age45.42±12.9 years. Lymphopenia (50%), alopecia (39%), arthritis (32%) and leukopenia (32%)were the most common clinical manifestations. The active SLE was present in 51 (49.5%)subjects. The control group consisted of 99 participants, mostly women (88%), average age55.43±13.62 years. Active EBV infection was significantly more often in subjects with SLE(41.7%) compared to the controls (9.2%). Subjects with SEL had a higher prevalence and titer ofanti-VCA IgM, anti-EA(D) IgG and anti-EA(D) IgM antibodies compared to the control group(p<0.001, p<0.001, p=0.008, respectively). Although the prevalence of active EBV infection insubjects with active SLE (47.1%) was higher compared to subjects in remission/LLDAS (36.5%),this difference was not statistically significant (p=0.321)...

Jezik

srpski

Datum

2023

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Imunologija i alergologija

systemic lupus erythematosus (SLE), Epstein-Barr Virus (EBV), anti-EBNA 1 IgG, anti-VCA IgM/IgG, anti-EA(D) IgM/IgG, EBNA1, LMP1, IL10RA, IL10RB, IL22RA

OSNO - Opšta sistematizacija naučnih oblasti, Imunologija i alergologija

sistemski eritemski lupus (SEL), Epštajn-Bar virus (EBV), anti-EBNA 1 IgG, anti-VCA IgM/IgG, anti-EA(D) IgM/IgG, EBNA1, LMP1, IL10RA, IL10RB, IL22RA

616-002.52-097(043.3)