Naslov (srp)

Značaj biomarkera i specifičnih dijagnostičkih procedura u ranom otkrivanju i različitoj fenotipskoj ekspresiji Takajaši arteritisa : doktorska disertacija

Autor

Stojanović, Maja, 1977-

Doprinosi

Vojvodić, Danilo, 1963-
Rašković, Sanvila, 1959-
Perić-Popadić, Aleksandra, 1961-
Bolpačić, Jasna, 1961-

Opis (srp)

Uvod: Takajaši arteritis (TA) je idiopatska, zapaljenska bolest hroničnog toka,koja se karakteriše granulomatoznim zapaljenjem aorte i njenih grana. Određenigenetički faktori mogu imati značaja u nastanku TA. Sekundarni antifosfolipidnisindrom (AFS) se može javiti u sklopu TA i karakteriše se vaskularnim i/ilikomplikacijama u vezi sa trudnoćom i/ili porođajem, u prisustvu antifosfolipidnih (AF)antitela. U dijagnostici i praćenju ovih bolesnika se primenjuje ehosonografski (EHO)Doppler pregled krvnih sudova, kompjuterizovana tomografija sa kontrastnomangiografijom (CTA) i poslednjih godina, poziciona emisiona tomografija u kombinacijisa niskorezolutivnom komjuterizovanom tomografijom uz primenu radioobeleživača -fluorodeoksiglukoze (18FDG PET-CT). Za procenu aktivnosti bolesti se najčešće koristeklinički skor NIH (National Institute of Health) i Indijski skor aktivnosti TA (IndianTakayasu’s Arteritis score, ITAS2010). Progresija bolesti se može indirektno proceniti iprimenom skorova: Indeksa ošećenja kod vaskulitisa (Vasculitis Damage Index, VDI),Indeksa oštećenja za pacijente sa TA (Takayasu Arteritis Damage Score, TADS) iKombinovanog skora oštećenja kod pacijenata sa arteritisom (Combined ArteritisDamage Score, CARDS). Pouzdani serumski biomarkeri vaskularnog i/ili sveukupnooštećenja do sada nisu identifikovani.Ciljevi istraživanja: Identifikacija biomarkera i dijagnostičkih procedura odznačaja za postavljanje dijagnoze i praćenje toka TA; analiza genetičkih faktora ibiomarkera koji bi mogli da se dovedu u vezu sa različitom fenotipskom ekspresijom,statusom aktivnosti, odgovorom na primenjene različite modalitete lečenja i pojavomkomplikacija bolesti.Pacijenti i metode: Ovom studijom preseka obuhvaćeno je 33 pacijenata sa TA;dijagnoza je postavljena na osnovu klasifikacionih kriterijuma Američkog koledža zareumatologiju (American College of Rheumathology, ACR) iz 1990. godine za adultnepacijente, i kriterijuma EULAR/PRINTO/PRES za pedijatrijski uzrast. DNK je izolovanaiz periferne krvi korišćenjem automatizovanog sistema Maxwell 16 Purification Kit.Tipizacija humanih leukocitnih antigena (Human Leucocyte Antigens, HLA) je učinjenakorišćenjem oligonukleotidnih proba koje su specifične za sekvencu (Sequence-specificoligonucleotide, SSO). Dobijena p vrednost je korigovana primenom Benjamini-Hochberg metoda. Polimorfizam TNF (Tumor necrosis factor) gena (rs1800692) jeispitivan TaqMan metodom sa komercijalno dostupnom smešom (#C__514879_10).Koncentracije aminoterminalnog propeptida prokolagena tipa III (Aminoterminalpropeptide of procollagen type III, PIIINPI), hijaluronske kiseline (Hyaluronic acid, HA),i tkivnog inhibitora matriksne metaloproteinaze-1 (Tissue Inhibitor of MatrixMetalloproteinase-1, TIMP-1) su analizirane pomoću imunoeseja ADVIACentaur®, askor ELF (Enchanced Liver Fibrosis) je automatski izračunavan prema proizvođačkojspecifikaciji. Takođe, analizirani su rezultati imidžing dijagnostike, antikardiolipinskih(AclA), antitela protiv β2 glikoproteina 1 (β2GPI), lupus antikoagulansa (LA) i rutinskihbiohumoralnih parametara.Rezultati: Ispitanike je činilo 93,9% osoba ženskog pola. Prosečna starostiznosila je 43,9±16,3 godina, uz medijanu kašnjenja u postavljanju dijagnoze od 2 (1-4,5) godine, u odnosu na pojavu prvih simptoma...

Opis (srp)

Medicina - Zapaljenje i autoimunost / Medicine- Inflammation and autoimmunity Datum odbrane: 17.06.2022.

Opis (eng)

Introduction: Takayasu arteritis (TA) is a chronic, idiopathic, inflammatorydisease, characterized by granulomatous inflammation of the aorta and its branches.Certain genetic factors may play an important role in the development of TA. Secondaryantiphospholipid syndrome (APS) may occur in patients with TA and it is characterizedby vascular and/or complications related to pregnancy and/or delivery, in the presenceof antiphospholipid (AP) antibodies. Echosonographic (ECHO) Doppler examination,computed tomography with contrast angiography (CTA), and the positional emissiontomography combined with a low-resolution computed tomography using thefluorodeoxyglucose (18FDG PET-CT), can be used for diagnosis and monitoring inpatients with TA. The NIH (National Institute of Health) clinical score and the IndianTakayasu’s Arteritis score (ITAS2010) are used the most often for assessing diseaseactivity. Disease progression can be assessed using the Vasculitis Damage Index (VDI),Takayasu Arteritis Damage Score (TADS) and Combined Arteritis Damage Score(CARDS). Serum biomarkers reflecting vascular and/or overall progression of thedisease have not been identified so far.Objectives: This study aimed to identify serum biomarkers and diagnosticprocedures relevant for diagnosis and disease monitoring; analysis of genetic factorsand biomarkers that might be related to different phenotypic expression, diseaseactivity status, response to different treatment and disease related complications.Patients and methods: This cross-sectional study included 33 patients with TA;the diagnosis was made according to the 1990 American College of Rheumatology(ACR) classification criteria for adults, and the EULAR/PRINTO/PRES criteria forpediatric patients. DNA was isolated from peripheral blood using the automatedMaxwell 16 Purification Kit. Human Leukocyte Antigens (HLA) typing was performedusing the sequence-specific oligonucleotide (SSO) probes; p values were corrected usingthe Benjamini-Hochberg method. TNF (Tumor necrosis factor) gene polymorphism(rs1800692) was examined using the TaqMan method with a commercially availablemixture (# C__514879_10). Concentrations of Aminoterminal Propeptide ProcollagenType II (PIIINPI), Hyaluronic Acid (HA), and Tissue Inhibitor of MatrixMetalloproteinase-1 (TIMP-1) were analyzed using the ADVIACentaur®, and the ELF(Enhanced Liver Fibrosis) score is automatically calculated according to themanufacturer's specification. The results of imaging procedures, routine serologyparameters and AP antibodies: anticardiolipin (AclA), antibodies against β2glycoprotein 1 (β2GPI) and lupus anticoagulants (LA) were also analyzed.Results: Of all patients, 93.9% were females with an average age of 43.9 ± 16.3years, and a median delay in diagnosis of 2 (1-4.5) years from the appearance of the firstsymptoms. The HLA-B*52, HLA-A*32, HLA-B*15, HLA-B*57, and HLA-C*03 alleles, andDRB1*15:02-DQB1*05 haplotype were more frequent in TA than controls, althoughonly HLA-B*52 remained significance after the statistical correction. HLA-B*52 allele inthe TA group was 10% (5/50), while it was present in 1.2% controls (46/3984) (p =0.0004, padj = 0.011). Carriage of HLA-B*52 was associated with a significantly earlierdisease onset and more severe clinical presentations. Carriers of HLA-C*03 experienceda milder clinical form of the disease...

Jezik

srpski

Datum

2022

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

Takajaši arteritis, Vaskulitis, HLA, Anti kardiolipinska antitela, Anti β2GPI antitela, Lupus antikoagulans, TNF (rs1800629), CT angiografija, 18FDG PET CT, ELF, TIMP-1, PIIINP, hijaluronska kiselina, VDI, TADS, CARDS, ITAS2010

616.13-002-07(043.3)

OSNO - Opšta sistematizacija naučnih oblasti, Imunologija i alergologija

Takayasu arteritis, Vasculitis, HLA; TNF (rs1800629), Anti cardiolipin antibodies, Anti β2GPI, Lupus anticoagulant, CT angiography, 18FDG PET CT, ELF, TIMP- 1, PIIINP, HA, VDI, TADS, CARDS, ITAS2010