Sanja Mitrović (Author), Matjaž Jeras (Mentor), Philip Bergin (Co-mentor)

Abstract

Despite more than 30 years of scientific and medical efforts, HIV infection is still a major global public health concern. The HIV pandemic continues to expand, with an average of 2,5 million new infections per year. Sub-Saharan Africa, including Rwanda, remains the most affected region in the world, accounting for approximately 70% of all people living with HIV. Therefore, safe and effective HIV prevention methods for Africa are urgently needed. A number of studies have shown that the cytokine network plays a crucial role in the pathogenesis of HIV infection. This raises the question whether cytokines in HIV disease can be a target for new approaches to develop a safe vaccine. The aim of our work was the assessment of potential protective biomarkers in serum and saliva samples of 14 HIV-1 infected participants from Rwanda. For this purpose, we used two methods to analyze our samples, i.e. the in-house ELISA test for detection of IgG and IgA antibodies against HIV-Gag p24 and HIV-Env gp140 proteins, and the Luminex Multiplex technology for measuring 15 soluble proteins involved in the Th17 immune response pathway (TNF-α, IL-6, IL-1β, IL-10, IFN-γ, IL-4, IL-17A, IL-17F, IL-17E, sCD40L, IL- 21, IL-22, IL-23, IL-31 and IL-33). Our results showed statistically significant correlations between serum concentrations of IL-6 and IgA anti-EnvA, as well as IL-33 and IgG anti- EnvA. Additionally, we found statistically significant correlations in saliva samples for IL- 1β with IgG anti-EnvA, IL-4 with IgG anti-EnvA and IgG anti-p24, IL-17A with IgA antip24, IL-17E with IgG anti-p24, and IL-23 with IgG anti-EnvA. Taken together, our results suggested that there are correlations between specific HIV-1 antibody and cytokine concentrations, indicating some potential protective biomarkers in HIV infection (IL-6, IL- 33, IL-1β, IL-4, IL-17A, IL-17E and IL-23). However, implicating cytokines in the development of an HIV cure is not a simple task and several limitations of our results should be noted. Therefore, further studies on the cytokine protective role in HIV disease are necessary to clarify their role in the real clinical conditions.

Keywords

HIV cytokines protective antibodies ELISA Luminex Multiplex method;

Data

Language: English
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL FFA - Faculty of Pharmacy
Publisher: [S. Mitrović]
UDC: 616.98:578.828(043.3)
COBISS: 4335473 Link will open in a new window
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Downloads: 170
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Other data

Secondary language: Slovenian
Secondary title: Assessment of potential protective biomarkers in serum and saliva samples of HIV-1 infected participants from Rwanda
Secondary abstract: Okužba z virusom HIV, kljub več kot 30 letom boja proti njej, še vedno ostaja eden večjih javnozdravstvenih problemov na svetu. Epidemija okužb z virusom HIV narašča v obsegu približno 2,5 milijona novih primerov na leto. Podsaharska Afrika, vključno z Ruando, ostaja najbolj prizadeta regija na svetu, kjer število ljudi, ki so okuženi z virusom HIV, predstavlja približno 70% vseh HIV-pozitivnih posameznikov na svetu. Zato zanj nujno potrebujemo varno in učinkovito cepivo. Pri okužbi z virusom HIV imajo pomembno vlogo citokini, topne proteinske signalne molekule, ki so del imunskega sistema. Citokini bi lahko bili uporabni pri iskanju novih pristopov za razvoj učinkovitega cepiva proti HIV. Seveda pa moramo najprej razumeti njihovo delovanje pri okužbi z virusom. To področje so že intenzivno raziskali, pri tem pa dobili nasprotujoče si rezultate. V okviru magistrske naloge smo določali prisotnost potencialnih zaščitnih označevalcev v serumu in slini 14 posameznikov iz Ruande, okuženih z virusom HIV. Pri tem smo primerjali koncentracije izbranih citokinov s titri specifičnih protiteles proti HIV. Uporabili smo dve metodi, test ELISA za detekcijo protiteles IgG in IgA proti proteinom HIV-Gag p24 in HIV-Env gp140 ter tehnologijo Luminex Multiplex za merjenje koncentracij 15 citokinov, ki sodelujejo v imunskih poteh celic Th17 (TNF-α, IL-6, IL-1β, IL-10, IFN-γ, IL-4, IL-17A, IL-17F, IL- 17E, sCD40L, IL-21, IL-22, IL-23, IL-31 in IL-33). Dokazali smo statistično značilne povezave med serumskimi koncentracijami IL-6 in protiteles IgA proti EnvA ter IL-33 in protiteles IgG proti EnvA. Poleg tega smo z meritvami citokinov v vzorcih sline potrdili tudi statistično značilne povezave med IL-1β ter protitelesi IgG proti EnvA, IL-4 in protitelesi IgG proti EnvA ter protitelesi IgG proti p24, IL-17A in protitelesi IgA proti p24, IL-17E in protitelesi IgG proti p24 ter IL-23 in protitelesi IgG proti EnvA. Zaključimo lahko, da pri preiskovanih osebah, okuženih s HIV, obstajajo povezave med koncentracijami citokinov (IL-6, IL-33, IL-1β, IL-4, IL-17A, IL-17E in IL-23) in titri protiteles razredov IgG in IgA proti HIV-Gag p24 in HIV-Env gp140. Sistemska uporaba citokinov v klinični praksi je zelo zahtevna. Statistično značilne povezave, ki smo jih odkrili, zato predvsem nakazujejo smer, v katero bi lahko usmerili nadaljnje raziskave, ki so nujno potrebne za boljše razumevanje morebitne zaščitne vloge posameznih citokinov pri okužbi z virusom HIV.
Secondary keywords: sindrom pridobljene imunske pomanjkljivosti;citokini;zaščitna protitelesa;ELISA;metoda Luminex Multiplex;AIDS;
Type (COBISS): Master's thesis/paper
Thesis comment: Univ. Ljubljana, Fak. za farmacijo
Pages: VIII, 33 f.
ID: 12034999