Serumski citokini u djece i odraslih s akutnom autoimunom trombocitopenijom

Čulić, Srđana (2004) Serumski citokini u djece i odraslih s akutnom autoimunom trombocitopenijom. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Background: The etiology of AITP is unknown and it is caused by an inappropriate response of the immune system. Antibody-coated platelets are removed from circulation by the monocytic phagocytic system, resulting in a shortened platelet survival. Aims: This study was designed to determine if these defects are related to serum cytokine levels, to evaluate the differences in serum cytokines between children and adults, to determine the correlation between cytokine serum concentrations and circulating lymphocytes, and antibodies to viruses. Subjects: The study population consisted of 48 children and 26 healthy controls, 19 adults with AITP and 24 healthy controls. Methods: Serum concentrations of IL-1α, -2, -3, -4, -6, -10, TNF-a, IFN-a, and IFN-g, antibodies against CMV, EBV, HHV-6, adenovirus and parvovirus B19 were all determined by ELISA; absolute lymphocyte count, percentage of circulating lymphocyte T, B, T4, T8 and NK cells by flow cytometric analysis were measured in children and adults with AITP at diagnosis. Data were analyzed by SPSS 11.0 PC and Statistica 6.0 statistical programs. Student’s t-test with logarithmic transformation comparing the data on cytokine levels was performed. Cytokines and platelets were measured at diagnosis, after 8 weeks and after 6 months while the Friedman test evaluated the changes. Pearson’s correlation coefficients and multiple regression analysis were used to predict the platelet values (after 6 months in children, after 8 weeks in adults). A p < 0,05 value was considered as statistically significant. Results: Concentrations of IL-2 (p = 0,021), TNF-α (p = 0,009) in children and IL-10 (p = 0,041) in adult patients were lower, while IL-4 (p = 0,062) in children and IL-1α (p = 0,0,045) in adults where higher, compared to healthy controls. Children with AITP had lower IL-4 (p = 0,033), IL-6 (p = 0,004) and IFN-γ (p = 0,001), and higher IFN-α (p = 0,007) then adults. Th lymphocytes in 52,6% children and 27,6% adults were low. The research revealed that after 6 months the number of platelets in children could be predicted by the number of platelets after 8 weeks and IL-3, IL-4 and TNF-α at diagnosis. After 8 weeks the number of platelets in adults could be predicted by apsolute lymphocyte count, B-lymphocytes, NK cells and IFN-α at diagnosis. Conclusion: Although the immunopathogenesis of AITP is autoantibody-mediated, there is now evidence that T helper cells and the cytokines they produce are involved.

Abstract in Croatian

Uvod: AITP je uzrokovana neadekvatnim imunim odgovorom nejasne etiologije. Trombociti obloženi protutijelima uklanjaju se iz cirkulacije pomoću monocitno makrofagnog sustava zbog čega kraće žive. Jedan od mogućih etioloških čimbenika je poremećaj ravnoteže citokina, koji je zamijećen u tih bolesnika. Ciljevi: Odrediti da li je imunosni defekt povezan sa serumskim koncentracijama citokina u djece i odraslih s akutnom AITP. Usporediti citokine pri dijagnozi u ispitanika međusobno i prema kontrolnoj skupini i odrediti promjene nakon 8 tjedana i nakon 6 mjeseci u oboljele djece i odraslih. Utvrditi povezanost razine citokina s prisustvom protutijela za CMV, EBV, HHV-6, adenovirus i parvovirus B19 i razine citokina s apsolutnim brojem limfocita, postotkom limfocita T, B, T4, T8 i NK stanica u oboljele djece i odraslih. Odrediti prognostičke vrijednosti razine citokina u odnosu na prelazak bolesti u kronični oblik u djece i odraslih. Ispitanici: Ispitivano je 48 djece i 19 odraslih s AITP. Kontrolnu skupinu sačinjavalo je 26 zdrave djece, te 24 zdrava odrasla. Metode: Koncentracije citokina IL-1α, -2, -3, -4, -6, -10, TNF-a, IFN-a, IFN-g, protutijela na CMV, EBV, HHV-6, adenovirus i parvovirus B19 su određeni u testu ELISA; apsolutni broj limfocita, postotak cirkulirajućih limfocita T, B, T4, T8 i NK stanice analizirani su pomoću protočnog razvrstavača stanica u djece i odraslih s AITP pri dijagnozi. Rezultati su analizirani pomoću statističkih programa SPSS 11.0 PC i Statistica 6.0. Studentov t-test s logaritamski transformiranim varijablama korišten je za usporedbu rezultata. Citokini i trombociti su mjereni pri dijagnozi, nakon 8 tjedana i nakon 6 mjeseci, a za evaluaciju promjena korišten je Friedmanov test. Pearsonov koeficijent korelacije i model višestruke regresije primijenjen je u predviđanju broja trombocita. Kao razina značajnosti korištena je vrijednost p < 0,05. Rezultati: Koncentracije IL-2 (p = 0,021), TNF-α (p = 0,009) u djece i IL-10 (p = 0,041) u odraslih su bile niže, a IL-4 (p = 0,062) u djece i IL-1α (p = 0,0,045) u odraslih su bile više od kontrolne skupine. Djeca s AITP su imala niži IL-4 (p = 0,033), IL-6 (p = 0,004) IFN-γ (p = 0,001), a viši IFN-α (p = 0,007) od odraslih. Limfociti T4 u 52,6% djece i 27,6% odraslih su bili sniženi. Broj trombocita u djece nakon 6 mjeseci bi se mogao predvidjeti pomoću broja trombocita nakon 8 tjedana, a IL-3, IL-4 i TNF-α pri dijagnozi. U odraslih bi se nakon 8 tjedana broj trombocita mogao predvidjeti pomoću IFN-α, apsolutnog broja limfocita, postotka limfocita B i NK stanica. Zaključak: U patogenezi AITP, pored autoprotutijela, sudjeluju i pomoćnički limfociti T, kao i citokini koje oni luče .

Item Type: Thesis (PhD)
Mentors:
Mentor
Labar , Boris
Departments: Izvan medicinskog fakulteta
Depositing User: dr.med. Helena Markulin
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 131
Status: Unpublished
Creators:
CreatorsEmail
Čulić, SrđanaUNSPECIFIED
Date: 22 December 2004
Date Deposited: 03 Apr 2008
Last Modified: 23 Sep 2011 16:10
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/349

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