E-Selectin, and markers of HIV disease severity, inflammation and coagulation in treatment- naïve individuals living with HIV
| dc.contributor.advisor | Zemlin, A. E. | |
| dc.contributor.advisor | Ipp, H. | |
| dc.contributor.advisor | Erasmus, R. T. | |
| dc.contributor.author | Hoffman, Madelein | |
| dc.date.accessioned | 2015-12-07T14:12:15Z | |
| dc.date.available | 2015-12-07T14:12:15Z | |
| dc.date.issued | 2015-12 | |
| dc.description.abstract | ENGLISH SUMMARY: Background: E-selectin is an adhesion molecule that is expressed on the surface of activated endothelial cells. During inflammation the endothelial cells are activated, trafficking cells of the immune system through the endothelial wall to the point of inflammation. Human Immunodeficiency Virus (HIV) infection causes continuous and long term activation of the immune system and has an increased incidence of cardiovascular disease. Selectins play an important role in atherosclerotic plaque formation as continuous activation leads to plaque formation and eventual plaque rupture with subsequent thrombosis and the initiation of a cardiac event. The aim of this study was to determine the levels of E-selectin in an HIV infected and control population and to correlate these levels with markers of HIV disease severity, inflammation and coagulation in anti-retroviral treatment (ART)-naïve HIV infected individuals. Methods: E-selectin levels were determined using ELISA in 180 participants from an HIV prevention and testing clinic in Crossroads, Cape Town. There were 114 HIV infected cases and 66 HIV negative controls. These levels were compared with each other and correlated to various other markers associated with HIV disease severity (viral load and CD4+count), inflammation (white cell count (WCC), high sensitivity C-reactive protein (hsCRP), %CD38/8, albumin and IgG) and coagulation (fibrinogen and D-dimer). Results: A total of 75% of the females tested positive for HIV compared to 37% of the males. Statistics comparing HIV status with WCC, CD4+count, %CD38/8, albumin, IgG, hsCRP and D-dimer found significant differences (p<0.01) between the two groups. No differences in E-selectin (p=0.84) and fibrinogen (p=0.65) levels were found between the cases and the controls. When E-selectin was compared with all the analytes tested, significant correlations were found with age (p=0.02) and gender (p=0.01). Albumin (p=0.05) showed a significant correlation with E-selectin in the control group. The correlation with the WCC (p=0.07) in the HIV infected group neared significance. Conclusion: No significant difference in E-selectin levels was found between the HIV positive and negative control group and no correlations were found with Eselectin and the markers of disease severity, inflammation and coagulation. Thus we found E-selectin to be a poor marker of inflammation in this setting. As age and gender are established markers of CVD and males have higher E-selectin levels than females, the lack of significance may be due to our sample population’s young age (mean 31 years) or the fact that 70% of the cohort was female. Thus significant endothelial damage may not yet have taken place to increase E-selectin levels. In addition, this HIV group was predominantly in the chronic stage of infection, therefore the increase in E-selectin levels may have occurred earlier during the acute infection. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Agtergrond: E-selektien is ‘n adhesie molekule wat teenwoordig is op die sel oppervlakte van geaktiveerde endoteelselle. Gedurende inflammasie word die endoteelselle geaktiveer en selle van die immuunstelsel beweeg deur die endoteellaag na die area van inflammasie. Menslike-immuungebreksvirus (MIV) veroorsaak aanhoudende en langdurige aktiveering van die immuunstelsel. Selektiene speel ‘n baie belangrike rol in arterosklerotiese plaak vorming, aangesien aanhoudende immuun aktivering bydra tot plaak vormasie. Uiteindelik raak die plaak onstabiel en breek oop met gevolglike bloedklont vorming en die aanvang van ‘n kardiale gebeurtenis. Die doel van die studie was om die vlak van E-selektien vas te stel in MIV infeksie en negatiewe kontroles en dit te korreleer met merkers van die graad van MIV infeksie, inflammasie en bloedstolling in anti-retrovirale terapie (ART) naief MIV geinfekteerde individue. Metodes: E-selektien vlakke is bepaal met behulp van ensiem gekoppelde immunosorbent toets (EGIST) in 180 deelnemers wat ‘n MIV voorkomings en toetsings kliniek in Crossroads, Kaapstad bygewoon het. Daar was 114 MIV positiewe gevalle en 66 MIV negatiewe kontroles. Die gevalle en kontroles is gekorreleer met mekaar en verskeie ander merkers wat geassosieer word met die graad van MIV infeksie (virale lading en CD4+telling), inflammasie (witsel telling (WST), hoe-sensitiewe C-reaktiewe proteïen (hsCRP); %CD38/8, albumien en IgG) asook bloedstolling (fibrinogeen en D-diemer). Resultate: ‘n Totaal van 75% vroulike deelnemers in vergelyking met 37% manlike deelnemers het positief getoets vir MIV. Statistiese korrelasies wat MIV status vergelyk het met die WST, CD4+telling, %CD38/8, albumien, IgG, hsCRP en Ddiemer vlakke het noemenswaardige verskille (p<0.01) getoon tussen die twee groepe. Geen verskille in E-selektien (p=0.84) en fibrinogeen (p=0.65) vlakke is gevind tussen the gevalle en kontroles nie. Toe E-selektien vergelyk is met al die analiete, is betekenisvolle korrelasies gevind met ouderdom (p=0.02) en geslag (p=0.01). Albumien (p=0.05) het betekenisvolle korrelasie getoon met E-selektien in die kontrole groep. En die WST (p=0.07) het ‘n tendens van korrelasie met Eselektien getoon in die MIV geinfekteerde group. Gevolgtrekking: Ons het geen betekenisvolle verskille in die E-selektien vlakke gevind tussen die twee groepe, of toe dit vergelyk is met die merkers van die graad van MIV infeksie, inflammasie en bloedstolling nie. Dus het ons vasgestel dat Eselektien ‘n swak merker van inflammasie in hierdie omstandighede is. Aangesien ouderdom en geslag vasgestelde merkers van kardiovaskulere siekte is en mans hoer E-selektien vlakke het teenoor vrouens, mag die gebrek aan betekenisvolle verskille as gevolg van die toets populasie se jong ouderdom (gemiddeld 31 jaar) wees, of die feit dat 70% van die deelnemers vroulik was. Ons vermoed dat endoteel skade nog nie ernstig genoeg was om verhoogte vlakke van E-selektien te weerspïeel nie. Daarbenewens, was hierdie MIV groep oorheersend al in die chroniese fase van infeksie, dus kon verhoogte vlakke van E-selektien dalk in die vroeer stadium van akute infeksie plaasgevind het. | af_ZA |
| dc.description.version | Masters | |
| dc.format.extent | ix, 103 pages : illustrations, includes annexures | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/97668 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject.lcsh | HIV infections -- South Africa | en_ZA |
| dc.subject.lcsh | Highly active antiretroviral therapy | en_ZA |
| dc.subject.lcsh | Anti-retroviral treatment | en_ZA |
| dc.subject.lcsh | UCTD | |
| dc.title | E-Selectin, and markers of HIV disease severity, inflammation and coagulation in treatment- naïve individuals living with HIV | en_ZA |
| dc.type | Thesis | en_ZA |