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Uvod: Bolesnici s pSS-om imaju povećanu prevalenciju endotelne disfunkcije i preuranjene ateroskleroze, a posljednjih godina je u fokusu istraživanja subklinička ateroskleroza u bolesnika s autoimunim bolestima. Nedavno je otkriven adropin, sekretorni protein koji ima značajnu ulogu u regulaciji metabolizama lipida i inzulinskoj rezistenciji, a isto tako ispoljava pozitivan učinak na funkciju endotelnih stanica te ima protuupalni učinak. Povišene razine homocisteina pokazale su se kao jak i neovisan čimbenik kardiovaskularnog rizika u zdravoj populaciji. Homocistein se pokazao i kao neovisan faktor rizika za razvoj subkliničke ateroskleroze. Korištenje CIMT-a, valjanog markera generalizirane ateroskleroze i rizika od vaskularne bolesti, može pomoći u identificiranju visokorizičnih bolesnika sa subkliničkom aterosklerozom. Cilj: Cilj ovog istraživanja bio je odrediti razine adropina i homocisteina te CIMT-a u bolesnika s pSS-om u usporedbi s kontrolnom skupinom. Nadalje, ciljevi su bili istražiti povezanoti između adropina, homocisteina i CIMT-a s imunološkim parametarima u pSS-u, uključujući protutijela specifična za bolest, EULAR-ov indeks aktivnosti bolesti u Sjögrenovom sindromu (ESSDAI) i indeks oštećenja bolesti u Sjögrenovom sindromau (SSDDI). Metode: U ovom presječnom istraživanju uključeno je 52 bolesnika s pSS-om i 52 ispitanika u kontrolnoj skupini usporedni s ispitivanom grupom po dobi, spolu, pušenju i ITM-u. Za dio istraživanja o homocisteinu uključeno je 48 bolesnika s pSS-om i 46 ispitanika u kontrolnoj skupini. Demografske varijable i klasični čimbenici kardiovaskularnog rizika: hipertenzija, dislipidemija, pretilost i navika pušenja procijenjeni su u obje skupine, a također su kliničkim pregledom i intervjuem prikupljene značajke povezane s bolešću u bolesnika s pSS-om. Za procjenu aktivnosti bolesti i kroničnog oštećenja su koristeni ESSDAI te SSDDI. Za analizu adropina je korištena enzimatska imunoanaliza (ELISA). Koncentracija homocisteina u serumu mjerena je korištenjem kemiluminiscentnog imunološkog testa mikročestica (CMIA). Prisutnost subkliničke ateroskleroze određena je CIMT-om procijenjenim ultrazvukom karotida. Rezultati: Bolesnici s pSS-om imaju značajno više razine adropina u usporedbi s kontrolnom skupinom (3,76 ± 0,68 naspram 3,14 ± 0,69 ng/mL, p < 0,001). Razine adropina u bolesnika s pSS-om su pozitivno povezane s HDL-om (r = 0,290, p = 0,036) i anti SSA/Ro52 antitijelima (r = 0,307, p = 0,026) te negativno povezane sa SSDDI ( r = −0,401, p = 0,003). 97 Multivarijantna linearna regresija pokazala je da su razine adropina neovisno povezane s HDL-om (β ± SE, 0,903 ± 0,283, p = 0,002) i SSDDI (β ± SE, -0,202 ± 0,073, p = 0,008). Arterijski tlak je bio viši u bolesnika s pSS-om (p = 0,007) za sistolički krvni tlak (SBD) i ()p = 0,018 za dijastolički krvni tlak (DBP). Suprotno od očekivanog, ukupni kolesterol (TC) bio je veći u kontrolnoj skupini (p = 0,047). Vrijednosti homocisteina bile su značajno veće u pacijenata s pSS-om (p=0,015), kao i CIMT (p=0,0372). Homocistein je pozitivno korelirao s trigliceridima (TG) (r=0,204, p=0,048) i CIMT-om (r= 0,231, p=0,046). CIMT je pozitivno povezan s dobi (r=0,416, p, Background: Patients with pSS have an increased prevalence of endothelial dysfunction and premature atherosclerosis, and in recent years the focus of research has been on subclinical atherosclerosis in patients with autoimmune diseases. Recently, adropin was discovered, a secretory protein that plays a significant role in the regulation of lipid metabolism and insulin resistance, and also has a positive effect on the function of endothelial cells and has an antiinflammatory effect. Elevated homocysteine levels have been shown to be a strong and independent cardiovascular risk factor in a healthy population. Homocysteine has also been shown to be an independent risk factor for the development of subclinical atherosclerosis. The use of CIMT, a valid marker of generalized atherosclerosis and risk of vascular disease, may help identify high-risk patients with subclinical atherosclerosis. Objective: The aim of this study was to determine the level of adropin and homocysteine and CIMT values in patients with pSS compared to healthy controls. Additional objectives were to investigate the correlation between adropin, homocysteine and CIMT with immunological parameters in pSS as disease-specific antibodies, EULAR Sjögren's syndrome disease activity index (ESSDAI) and Sjögren's syndrome disease damage index (SSDDI). Methods: In this cross-sectional study, 52 patients with pSS and 52 subjects in the control group were included, comparable in terms of age, sex, smoking and BMI. For the homocysteine part of the study, 48 patients with pSS and 46 subjects in the control group were included. Demographic variables and classic cardiovascular risk factors: hypertension, dyslipidemia, obesity and smoking habits were assessed in both groups, and features associated with the disease in the pSS group were also collected through clinical examination and interviews. ESSDAI and SSDDI were used to assess disease activity and chronic disease damage. Enzyme immunoassay (ELISA) was used to analyze adropin. Serum homocysteine concentration was measured using a chemiluminescent microparticle immunoassay (CMIA). The presence of subclinical atherosclerosis was determined by CIMT assessed by carotid ultrasound. Results: Patients with pSS have significantly higher adropin levels compared to controls (3.76 ± 0.68 vs. 3.14 ± 0.69 ng/mL, p < 0.001). Adropin levels in patients with pSS are positively correlated with HDL (r = 0.290, p = 0.036) and anti SSA/Ro52 antibodies (r = 0.307, p = 0.026) and negatively correlated with SSDDI (r = −0.401, p = 0.003). Multivariate linear regression showed that adropin levels were independently associated with HDL (β ± SE, 0.903 ± 0.283, p = 0.002) and SSDDI (β ± SE, -0.202 ± 0.073, p = 0.008). 100 Arterial pressure was higher in patients with pSS (p = 0.007) for systolic blood pressure (SBP) and (p = 0.018) for diastolic blood pressure (DBP). Contrary to expectation, total cholesterol (TC) was higher in the control group (p = 0.047). Homocysteine values were significantly higher in patients with pSS (p=0.015), as well as CIMT (p = 0.0372). Homocysteine positively correlated with triglycerides (TG) (r = 0.204, p = 0.048) and CIMT (r= 0.231, p=0.046). CIMT was positively correlated with age (r = 0.416, p < 0.0001), SBP (r=0.293, r=0.004) and with Sjögren's syndrome impairment index (SSDDI) (r = 0.351, p = 0.014). It also negatively correlated with Sjögren's syndrome-specific autoantibodies anti SSA/Ro60 (r = -0.431, p = 0.002) and anti SSB/La (r = -0.346, p = 0.016). Conclusion: Our findings are implying that patients with pSS have an increased risk for subclinical atherosclerosis and that adropin could be involved in the pathophysiology of pSS and the in mentioned processes by acting protectively on the endothelium. We also showed that there is a significant association between the subclinical atherosclerotic process and homocysteine. So, homocysteine could be a cheap and available marker for risk stratification of the development of subclinical atherosclerosis in asymptomatic patients. These results suggest that the inclusion of determination of plasma adropin and homocysteine levels in risk reduction protocols may be relevant to identify individuals at higher risk of atherosclerotic events. Ultimately, this would enable timely taking of preventive measures that would reduce the mentioned risks.

Primarni je Sjögrenov sindrom (pSS) autoimuna, multi-organska bolest koja se u prvom redu očituje osjećajem suhih očiju i suhih usta, zbog kronične upale žlijezda slinovnica. Razvoj non-Hodgkinovog limfoma (NHL) smatra se jednim od najtežih simptoma bolesti. Poznato je da u usporedbi s općom populacijom, bolesnici sa pSS-om imaju povećan rizik od razvoja NHL-a. S obzirom na činjenicu da u Republici Hrvatskoj (RH) još nema objavljenih epidemioloških podataka o učestalosti NHL-a u osoba sa pSS-om, cilj ovog istraživanja bio je odrediti stopu incidencije NHL-a kod bolesnika sa pSS-om liječenih u Kliničkom bolničkom centru Zagreb (KBC Zagreb) i ustanoviti obolijevaju li ti bolesnici od NHL-a više od opće populacije RH. Pregledani su medicinski kartoni pacijenata KBC-a Zagreb sa šifrom dijagnoze M35.0. Zatim, kako bi se pronašli pacijenti sa pSS-om i NHL-om, podatci su se tih pacijenata dodatno usporedili s elektroničkim medicinskim zapisima pacijenata sa šiframa dijagnoza od C81 do C96. U studiju su uključene 92 osobe koje su ispunjavale zajedničke kriterije Američkog reumatološkog društva i Europske lige protiv reumatizma iz 2016. godine za dijagnozu pSS-a. Prosjek godina praćenja pacijenata sa pSS-om iznosio je 13 godina. Od NHL-a su oboljele 3 pacijentice, dvije u dobi od 44 godine, a jedna u dobi od 49 godina, dok nitko u skupini muškaraca sa pSS-om nije obolio od NHL-a. Ukupna stopa incidencije NHL-a iznosila je 334 na 100000 bolesnik-godina. Nakon provedene neizravne standardizacije prema stopi incidencije NHL-a u općoj populaciji RH, standardizirani omjer incidencija iznosio je 17,6. Velika stopa incidencije NHL-a u populaciji osoba sa pSS-om liječenih u KBC-u Zagreb te podatak o njegovoj 17 puta većoj pojavnosti od one u općoj populaciji Hrvatske važni su za sve liječnike uključene u praćenje ovih bolesnika., Primary Sjögren’s syndrome (pSS) is an autoimmune, multi-organ disease which results in chronic inflammation of mostly salivary and lacrimal glandular epithelium. One of the most severe extra-glandular symptoms of a disease is development of a non-Hodgkin’s lymphoma (NHL). Compared to the general population, patients with pSS have an increased risk of developing NHL. By now, studies of NHL incidence among pSS patients have not been published in the Republic of Croatia. The aim of this study was to calculate an incidence rate of a NHL among all pSS patients at the University Hospital Centre Zagreb, and to determine whether these patients suffer from NHL more than the general population of the Republic of Croatia. Medical records of patients with diagnosis code M35.0 were examined. The data of these patients were then compared with medical records of patients with diagnosis codes from C81 to C96, in order to find patients with pSS and NHL. The study included 92 individuals who met the 2016 American College of Rheumatology and European League Against Rheumatism Classification criteria for the diagnosis of pSS. The mean follow-up of patients was 13 years. NHL affected 3 female patients, two at the age of 44 and one at the age of 49. The overall incidence rate of NHL was 334 per 100,000 patient-years. After performing the indirect standardization, standardized incidence ratio was 17.6. High incidence rate of NHL among the population of patients with pSS treated at University Hospital Centre Zagreb and the data on its 17 times higher incidence than in the general population of Croatia is important for all physicians involved in monitoring these patients.