Calprotectin (S100A8/A9) as a marker of inflammation and treatment monitoring in cases of juvenile idiopathic arthritis in the Western Cape, South Africa

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dc.contributor.advisorGlashoff, Richard H. en_ZA
dc.contributor.advisorAbraham, Deepthi Rajuen_ZA
dc.contributor.authorEvert, Christineen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Microbiology.en_ZA
dc.date.accessioned2023-03-03T16:07:31Z
dc.date.accessioned2023-05-18T07:07:46Z
dc.date.available2023-03-03T16:07:31Z
dc.date.available2023-05-18T07:07:46Z
dc.date.issued2023-03
dc.descriptionThesis (MSc)--Stellenbosch University, 2023. en_ZA
dc.description.abstractENGLISH ABSTRACT: Background: Juvenile Idiopathic Arthritis (JIA) is a common rheumatic disease affecting children and is characterised by persistent inflammation of the joints. The socio-economic climate of South Africa can delay access to treatment to achieve remission. Joint inflammation is currently monitored through C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) measurements. Recent studies have shown that these markers may correlate less well with disease activity than calprotectin. Calprotectin is released by activated monocytes or macrophages at the site of joint damage and binds the TLR4 surface receptor. This protein has also been used to detect subclinical inflammation and may predict risk of relapse. This study aimed to compare standard markers of inflammation with calprotectin, and its relation to other inflammatory markers. Methodology: Blood samples were collected from 22 consented JIA participants. Clinical information and history for each participant was obtained from patient files at Tygerberg Hospital. Monocyte distribution and phenotypic marker expression was investigated using whole blood for surface marker flow cytometry. Plasma levels of calprotectin and JIA associated inflammatory markers (including CCL2, CCL11, CD163, CXCL9, CCL3, CCL22, CD25, CXCL10, IL-1β, MIF, IL12, TNF-α and IFN-γ) were assessed by means of ELISA and Luminex™ multiplex assays. Routine CRP and ESR results were collected from the NHLS TrakCare database. For longitudinal follow up, blood samples were collected from the same cohort 6 months later and assays were repeated. A study database was created with all participant results, at both visits, to investigate relationships between calprotectin and JIA disease activity, as well as the effect of treatment over time. Results: The majority (95%) of participants were already undergoing treatment. Calprotectin was within the normal range for children (127 – 1395 ng/mL) in 86% of baseline samples with a median of 628.6 ng/mL (IQR: 406.2 - 979.8). Only ESR changed significantly (p=0.0079) over time and showed the most evidence for changes in inflammation thereby inspiring analysis by stratification. To evaluate impact of disease phenotype (active vs. remission) and inflammatory state based on ESR expression (high vs. low ESR), participants were stratified into respective groups and compared. Expression of intermediate monocytes at baseline was higher than the expected range (2 - 10 %), with a median of 27 % (IQR: 9 - 43). This distribution is characteristic of inflammatory diseases. Calprotectin correlated significantly (p<0.05) with CRP and ESR at baseline in the returning, remission and high ESR analysis groups. Several notable cases displaying high calprotectin expression were linked to a relapse in disease. Conclusions: Despite limitations, this study confirmed the predictive value of calprotectin in risk of disease relapse and the need for such a marker in the clinical setting to allow for a more tailored approach to treatment. The relationship between intermediate monocyte expansion, calprotectin and disease phenotype also needs to be examined further. Future studies which include treatment naïve participants would be beneficial in assessing the usefulness of calprotectin in monitoring response to treatment.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Agtergrond: Jeugdige idiopatiese artritis (JIA) is 'n algemene rumatieksiekte wat kinders affekteer en word gekenmerk deur aanhoudende inflammasie van die gewrigte. Die sosio-ekonomiese klimaat van Suid-Afrika kan toegang tot behandeling, om remissie te bewerkstellig, vertraag. Gewrigsontsteking word tans gemonitor deur C-reaktiewe proteïen (CRP) en eritrosiet sedimentasietempo (ESR) metings. Onlangse studies het getoon dat hierdie merkers nie so goed soos kalprotektien (KP) met siekte-aktiwiteit korreleer nie. KP word vrygestel deur geaktiveerde monosiete of makrofage op die plek van gewrigskade en bind die TLR4-oppervlakreseptor. Hierdie proteïen is ook gebruik om subkliniese inflammasie op te spoor en kan die risiko van terugval voorspel. Hierdie studie het ten doel gehad om standaardmerkers van inflammasie met KP te vergelyk, en dié se verband met ander inflammatoriese merkers. Metodes: Bloedmonsters is van 22 ingestemde JIA-deelnemers ingesamel. Kliniese inligting is verkry uit pasiëntlêers te Tygerberg Hospitaal. Monosietverspreiding en fenotipiese merkeruitdrukking is ondersoek deur gebruik van volbloed vir vloeisitometrie. Plasmavlakke van KP en JIA-geassosieerde inflammatoriese merkers (insluitend CCL2, CCL11, CD163, CXCL9, CCL3, CCL22, CD25, CXCL10, IL-1β, MIF, IL12, TNF-α en IFN-γ) is deur middel van ELISA en Luminex™ multiplekstoetse geassesseer. Roetine CRP en ESR resultate is versamel van die NHLS TrakCare databasis. Vir opvolg, is bloedmonsters van dieselfde kohort 6 maande later versamel en toetse is herhaal. 'n Databasis is geskep met alle deelnemers’ resultate, by beide besoeke, om verwantskappe tussen KP en JIA-siekteaktiwiteit te ondersoek, asook die effek van die behandeling. Resultate: Die meerderheid (95%) van die deelnemers het reeds behandeling ondergaan. KP was binne die normale omvang vir kinders (127 – 1395 ng/mL) in 86% van basislynmonsters met 'n mediaan van 628.6 ng/mL (IQR: 406.2 - 979.8). Slegs ESR het beduidend verander (p=0.0079) met verloop van tyd en het die meeste bewyse getoon vir veranderinge in inflammasie en sodoende analise deur stratifikasie geïnspireer. Om die impak van siekte fenotipe (aktiewe vs. remissie) en inflammatoriese toestand te evalueer gebaseer op ESR uitdrukking (hoë vs. lae ESR), is deelnemers gestratifiseer en vergelyk. Uitdrukking van intermediêre monosiete by basislyn was hoër as die verwagte reeks (2 - 10 %), met 'n mediaan van 27 % (IQR: 9 - 43). Hierdie verspreiding is kenmerkend van inflammatoriese siektes. KP het betekenisvol (p<0.05) gekorreleer met CRP en ESR by basislyn in die terugkeer, remissie en hoë ESR analise groepe. Verskeie noemenswaardige gevalle wat hoë KP uitdrukking toon, is gekoppel aan 'n terugval in siekte. Gevolgtrekkings: Ten spyte van beperkings, het hierdie studie die voorspellende waarde van KP in risiko van siekte-terugval bevestig. 'n Meer pasgemaakte benadering tot behandeling is moontlik deur gebruik van hierdie merker. Die verband tussen intermediêre monosietuitbreiding, KP en siektefenotipe moet ook verder ondersoek word. Toekomstige studies wat behandelingsnaïewe deelnemers insluit, sal voordelig wees om die bruikbaarheid van KP in die monitering van reaksie op behandeling te bepaal.af_ZA
dc.description.versionMastersen_ZA
dc.format.extentxiii, 104 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/127167
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshCalprotectinen_ZA
dc.subject.lcshRheumatoid arthritis in children -- Treatmenten_ZA
dc.subject.lcshJuvenile idiopathic arthritis -- South Africa -- Western Capeen_ZA
dc.subject.lcshRheumatism - Economic aspects -- South Africaen_ZA
dc.subject.lcshHuman beings -- Effect of climate onen_ZA
dc.subject.lcshArthritis -- Environmental aspectsen_ZA
dc.subject.lcshInflammationen_ZA
dc.subject.nameUCTDen_ZA
dc.titleCalprotectin (S100A8/A9) as a marker of inflammation and treatment monitoring in cases of juvenile idiopathic arthritis in the Western Cape, South Africaen_ZA
dc.typeThesisen_ZA
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