<p>Uvod: Nespecifičnost kliničke slike sepse, velike individualne razlike u odgovoru organizma na infekciju kao i neophodnost adekvatne inicijalne procene težine kliničke slike, toka i ishoda bolesti, čine istraživanja biomarkera koji bi doprineli pravovremenom postavljanju dijagnoze i adekvatnoj prognozi bolesti izuzetno značajnim. Do sada je ispitivano preko 200 biomarkera od kojih ni jedan nije pokazao zadovoljavajuću senzitivnost i specifičnost. Uloga B limfocita u patogenezi sepse pri tome je nedovoljno istražena. Članovi superfamilije tumor-nekrozis faktora alfa: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) i solubilni transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) su citokini koji imaju ključnu ulogu u homeostazi B limfocita. Cilj istraživanja bio je da se ispita dijagnostički i prognostički značaj citokina članova superfamilije tumor nekrozis faktora alfa (APRIL, BAFF, sTACI) za procenu težine kliničke slike, razvoja multiorganske disfunkcije (MODS) u prvih 48h hospitalizacije i letalnog ishoda sepse. Ispitanici i metode: Istraživanjem je obuhvaćeno 150 obolelih od sepse lečenih na Klinici za infektivne bolesti i Odeljenju anestezije i reanimacije Kliničkog centra Vojvodine i 30 zdravih dobrovljnih davalaca krvi. Kod svih bolesnika evidentirani su demografski i ostali podaci iz istorije bolesti kao i laboratorijske analize u okviru rutinske dijagnostike sepse. Iz dodatnih 5ml venske krvi svim ispitanicima određene su koncentracije APRIL-a, BAFF-a, sTACI-ja ELISA metodom komercijalnim testovima proizvođača R&D Systems. Rezultati pokazuju da su koncentracije sva tri citokina (APRIL, BAFF i sTACI) statistički značajno povišene kod obolelih od sepse u odnosu na zdravu populaciju (p<0.001), pri čemu APRIL pokazuje najveću senzitinvost (99%) i specifičnost (97%). Najveći dijagnostički značaj BAFF-a ogleda se u sposobnosti distinkcije između sepsi uzrokovanih Gram pozitivnim i Gram negativnim bakterijama (p=0,03). U predikciji razvoja MODS-a i letalnog ishoda sepse multivarijantnom regresionom analizom kao nezavisni prediktori pokazali su se jedino antiinflamatorni biomarker sTACI receptor i klinička procena pacijenta iskazana kroz APACHE II i SOFA skor. Senzitivnost i specifilnost sTACI receptora u predikciji razvoja MODS-a i letalnog ishoda daleko nadmašuje do sada rutinski korišćen prokalcitonin. Zaključak: Dobijeni rezultati ukazuju na to da su citokini koji učestvuju u regulaciji funkcije B limfocita značajni dijagnostički i prognostički parametri u sepsi. Predominacija antiinflamatornog odgovora na koju ukazuju povišene koncentracije sTACI receptora pokazala se pored APACHE II i SOFA skora kao jedini nezavisni prediktor razvoja MODS-a i letalnog ishoda septičnih bolesnika. Neophodna su dalja istraživanja u pravcu određivanja momenta kada u imunskom odgovoru organizam prelazi iz stanja dominacije proniflamatornog u dominaciju antiinflamatornog odgovora radi pravovremenog reagovanja imunomodulatornom terapijom.</p> / <p>Introduction: The nonspecific clinical presentation of sepsis and great individual response variations, as well as huge significance of adequate early prognosis of its clinical course and outcome made sepsis biomarkers research extremely significant. The properties of more than 200 biomarkers have been evaluated for prognostic value, but none have adequate specificity and sensitivity. The role of the B cells in sepsis pathogenesis also remains unclear. Tumor necrosis factor alpha (TNF-α) superfamily members: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) and soluble transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) are key factors in B cell biology. The aim of the study was to evaluate the diagnostic and prognostic significance of determining the concentrations of tumor necrosis factor alpha superfamily members for the prediction of MODS development in the first 48h of hospitalization as well as outcome prediction.<br />Subjects and methods: The study included 150 patients suffering from sepsis treated at the Clinic for infectious diseases and Department for anesthesiology and reanimatology of the Clinical center of Vojvodina, and 30 healthy volunteer blood donors. The demographic and other data regarding routine blood analysis performed during sepsis treatment of the patients has been acquired from their hospitalization documentation. Additional 5 ml of venous blood was taken from the patients and the concentrations of APRIL, BAFF and sTACI have been determined using the ELISA method by using R&D Systems commercial kit’s. Results: There is a statistically significant difference in concentrations of APRIL, BAFF and sTACI between healthy blood donors and septic patients (p<0.001). APRIL showed the highest sensitivity (99%) and specificity (97%) in distinguishing sepsis from healthy subjects. BAFF showed statistically significant higher concentrations in Gram positive than in Gram negative sepsis (p=0,03). In the multivariate logistic regression analysis, only anti-inflammatory cytokine sTACI and APACHE II or SOFA score remained significant predictors of MODS and lethal outcome. sTACI showed greater sensitivity and specificity for MODS and outcome prediction then the widely used procalcitonin. Conclusions: The concentrations of TNF superfamily members, the main regulators of B cell function, have a significant diagnostic and prognostic value in predicting sepsis course and outcome. The predomination of the anti-inflammatory response, as being pointed out by elevated concentrations of sTACI receptors, has proved to be the only independent predictor, besides APACHE II and SOFA score, in MODS and lethal outcome development in sepsis. Further research is needed in order to accurately determine the exact moment when the immunological response shifts from the predominance of the pro-inflammatory response to the predominance of the anti-inflammatory response, so as to ensure the timely application of therapy that modulates the immunological response.</p>
| Identifer | oai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)95447 |
| Date | 30 September 2015 |
| Creators | Lendak Dajana |
| Contributors | Brkić Snežana, Turkulov Vesna, Šurbatović Maja, Fabri Milotka, Mitic Igor, Vrbić Miodrag |
| Publisher | Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad |
| Source Sets | University of Novi Sad |
| Language | Serbian |
| Detected Language | Unknown |
| Type | PhD thesis |
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