Suradnici:
- Prof. dr. sc. Viktor Peršić, dr. med.
- Prof. dr. sc. Tatjana Kehler, dr. med.
- Prof. dr. sc. Nikša Dulčić, dr. dent. med.
- Dr. sc. Antonija Baršić Ružić, dr. med.
- Dr. sc. Iva Uravić Bursać, dr. med.
- Marija Rogoznica Pavlović, dr. med
- Vedrana Drvar, mag. med. biochem.
- Vedrana Tudor Špalj, dr. med.
- Mila Stazić, dr. med.
- Karla Vurić, dr. med.
Doktorandi
- Ana-Marija Laškarin, dr. dent. med.
- Ivan Rosović, dr. med.
- Silvija Miletić Gršković, dr. med.
Sažetak istraživanja:
Spondiloartritis (SpA) je grupa autoinflamatornih/autoimunih poremećaja, koja se javlja u genetski predisponiranih osoba pod utjecajem čimbenika okoline. Smatra se da počinje predočavanjem antigena mikrobioma probavne cijevi limfocitima T u prisutnosti interleukina (IL)-23, što u sluznici probavne cijevi potiče limfocite na lučenje IL-17. Stanice aktivirane u crijevima odlaze u cirkulaciju i djeluju sistemski, a najčešće naseljavaju zglobove i enteze te nishodno potiču lučenje brojnih proupalnih posrednika poput IL-22 i čimbenik nekroze tumora α (TNFα), IL-6, RANKL (od engl. receptor activator of nuclear factor kappa-β ligand), koji zauzvrat potiču upalu. SpA uvelike mijenja život bolesnika, jer je udružen s velikim brojem komorbiditeta, uključujući psorijazu, pretilost hiperlipoproteinemiju, šećernu bolest, kardiovaskularne (KV) bolesti, iridociklitis, osteoporozu, anksioznost, depresivne poremećaje, poremećaj sna, i kronični umor. SpA s komorbiditetima smanjuje radnu sposobnost i socijalno funkcioniranje bolesnika te neliječena znatno smanjuje kvalitetu i trajanje života. Međutim još uvijek je nedovoljno istražen međuodnos upale i komorbiditeta.
Pretpostavili smo da je aktivnost SpA u međuovisnosti s koncentracijama proupalnih tvari u slini i serumu te sa subkliničkim ili kliničkim pokazateljima KV bolesti i depresivnih poremećaja, koji u podlozi imaju endotelnu disfunkciju (ED).
Cilj istraživanja jest odrediti aktivnost SpA, KV komorbiditete (srčano zatajivanje, kroničnu koronarnu bolest, krutost aorte), pojavnost anksioznosti/depresije, i istražiti njihovu moguću povezanost s koncentracijama proupalnih citokina u slini i/ili serumu.
Aktivnost SpA će se utvrditi kao broj bolnih ili otečenih zglobova od 68, odnosno 66, jačina boli, jutarnja zakočenost, ASDAS (od engl. Ankylosing Spondylitis Disease Activity Score), DAPSA (od engl. Disease Activity in Psoriatic Arthritis), BASDAI (od engl. od eng. Bath Ankylosing Spondylitis Disease Activity Indeks), prisutnost temporomandibularnog poremećaja po dijagnostičkom kriteriju (DK/TMP), koji sadrži upitnike poput GAD-7 za anksioznost i PHQ-9 za depresiju. Učinit će se elektrokardiogram, pocjena ED (EuroScore, Framingham), antropometrija, izmjeriti brzina širenja pulsnog vala, transtorakalni ultrazvuk srca te Agatsonov broj, invazivna koronarografija i MR srca za kvantifikaciju upale, fibroze i prokrvljenosti po kardiološkim indikacijama. Iz seruma i sline bolesnika će se odrediti koncentracije proupalnih citokina, koji sudjeluju u patogenezi SpA i razgradnih proizvoda endotelnog glikokaliksa. Znanstveni značaj istraživanja bio bi u povezivanju koncentracije proupalnih biljega sa aktivnošću SpA i subkliničkim ili ranim kliničkim pojavnostima KV oboljenja i depresije. Klinička primjena sastojala bi se u ranom prepoznavanju mnogobrojnih kliničkih pojavnosti SpA-a, pravovremenom liječenju upale te probiru bolesnika za KV komorbiditete i depresivne poremećaje u svrhu ranog liječenja komorbiditeta u bolesnika sa SpA.
Abstract
Spondyloarthritis (SpA) is a group of autoinflammatory/autoimmune disorders, which occurs in genetically predisposed individuals under the influence of environmental factors. It is considered that SpA begins with the presentation of gut microbiome antigens to T cells in the presence of interleukin (IL)-23, which in gut musosa stimulate lymphocytes to secrete IL-17. The cells activated in the gut travel via circulation and act sistemically. They often settled joints and entheses and stimulate downstream the secretion of numerous pro-inflammatory mediators, such as IL-22 and tumor necrosis factor α (TNFα), IL-6, receptor activator of nuclear factor kappa-β ligand (RANKL) which in turn promote inflammation.
SpA greatly changes the life of patients, as it is associated with a large number of comorbidities, including psoriasis, obesity, hyperlipoproteinemia, diabetes, cardiovascular (CV) diseases, iridocyclitis, osteoporosis, anxiety, depressive disorders, sleep disorders and chronic fatigue. SpA with comorbidities reduces the patient’s work capacity and social functioning and, if untreated, significantly reduces the quality and duration of life. However, the relationship between inflammation and comorbidities is still insufficiently investigated.
We hypothesized that SpA activity is correlated with salivary and serum concentrations of proinflammatory substances and with CV comorbidities and depression, which are supported by endothelial dysfunction (ED). The aim of the study is to determine SpA activity, heart failure, chronic coronary disease, aortic stiffness, anxiety/depression, and to investigate their possible association with salivary and/or serum concentrations of proinflammatory cyzokines. SpA activity will be determined as the number of painful or swollen joints of 68 or 66, pain intensity, morning stiffness, Ankylosing Spondylitis Disease Activity Score, Disease Activity in Psoriatic Arthritis, Bath Ankylosing Spondylitis Disease Activity Indeks, presence of temporomandibular disorder according to diagnostic criteria (DC/TMD), which contains questionnaires GAD-7 for anxiety and PHQ-9 for depression. An electrocardiogram, ED assessment (EuroScore, Framingham), anthropometry, pulse wave velocity and transthoracic cardiac ultrasound will be performed. Agatson’s number, invasive coronary angiography and cardiac MR will quantify blood perfusion, inflammation and fibrosis according to cardiological indications. Salivary and serum concentrations of pro-inflammatory cytokines that participate in the pathogenesis of SpA and products of the endothelial glycocalyx will be analyzed.
The scientific significance of the research would be in linking the concentration of pro-inflammatory markers with SpA activity and CV comorbidities and depression.
Clinical application would consist in early recognition of numerous clinical manifestations of SpA, timely treatment of inflammation and screening of patients for CV comorbidities and depressive disorders for the purpose of early treatment of comorbidities in patients with SpA.
Dosadašnje aktivnosti:
