Easy-to-use diagnostic assays for thrombotic thrombocytopenic purpura

Quintijn Bonnez
Persbericht

Optische vezels, de gedroomde weg naar een vlotte diagnose

Glasvezels stonden meermaals in de spotlights dankzij hun maatschappelijke bijdrage in de voorziening van bijvoorbeeld snelle internetverbindingen, maar nu dringen nieuwe toepassingen ook door tot de klinische onderzoekswereld. Kunnen optische vezels een nieuw tijdperk inluiden voor de diagnose van auto-immuunziektes? De toekomst van deze innovatieve technologie oogt in elk geval rooskleurig!

De voorbije decennia is sterk ingezet op het ontwikkelen van testen voor de diagnose van auto-immuunziektes, zoals het uiterst zeldzame immuun-gemedieerde trombotische trombocytopenische purpura (iTTP). De huidige commerciële testen zijn ingewikkeld en worden daarom alleen in gespecialiseerde ziekenhuislaboratoria uitgevoerd. Bijgevolg zijn deze testen niet meteen beschikbaar als een iTTP patiënt is opgenomen in een plaatselijk ziekenhuis. Daarom is de arts gedwongen een voorlopige diagnose te formuleren in afwachting van het resultaat van de diagnostische testen. Ondertussen is bloed van de patiënt naar een gespecialiseerd ziekenhuislaboratorium opgestuurd, waar de diagnose van iTTP slechts 2 tot 5 dagen later is bevestigd. Aangezien een iTTP aanval levensbedreigend is, moet de diagnose binnen de 6 uur zijn geformuleerd, zodat de patiënt de correcte behandeling zo snel mogelijk krijgt toegediend. Bij de huidige diagnose is het risico dan ook groot dat patiënten een verkeerde diagnose en behandeling krijgen, waaruit blijkt dat er een tekort is aan eenvoudige en snelle testen. Dankzij nieuwe toepassingen, die gebruikmaken van de glasvezels, is het mogelijk testen te ontwikkelen die de correcte diagnose van iTTP in elk ziekenhuis kunnen aangeven.

Optische vezels

De innovatieve glasvezeltechnologie maakt gebruik van optische vezels, die met een dun laagje goud zijn bekleed. Licht valt in op de glasvezel, waarbij de goudlaag het licht breekt en reflecteert tot aan een detector. Vervolgens stuurt een geautomatiseerde robotarm de beweging van de optische vezels. Nadat de glasvezels in een bloedstaal van een patiënt zijn gebracht, binden biomoleculen uit het bloed aan de gouden glasvezel. Hierdoor neemt de detector een verandering waar in de breking van het gereflecteerde licht. Vervolgens volstaat het de veranderingen in de breking van het licht op te volgen om de interacties van biomoleculen waar te nemen. Op deze manier kan de nieuwe technologie de biologische parameters van patiënten opvolgen om een snelle, definitieve diagnose te kunnen stellen.

Trombotische trombocytopenische purpura

Bij iTTP keert het immuunsysteem zich tegen het eigen lichaam. In deze auto-immuunziekte ontbreekt een molecule, ADAMTS13 genaamd, dat als een schaar in het bloed functioneert. Door zijn afwezigheid kan deze schaar niet langer von Willebrand factor (vWF), een lijm-eiwit in het bloed, knippen. Bijgevolg stimuleert het vWF lijm-eiwit het vastkleven van bloedplaatjes uit de bloedsomloop, waardoor bloedklontertjes ontstaan die de bloedvaten afsluiten. Hoewel TTP een zeldzame aandoening is, resulteert de ziekte altijd in een spoedopname waarbij 10 tot 20 procent van de TTP patiënten een dodelijke afloop kent.

Hoe sneller een patiënt de juiste behandeling krijgt toegediend, hoe kleiner het risico op de vorming van de levensbedreigende bloedklontertjes. Aangezien elk uur bepalend kan zijn, is een snelle en correcte diagnose belangrijk voor iTTP patiënten. De huidige testen verlopen echter langzaam en zijn arbeidsintensief, waardoor alternatieve technieken zich opdringen. Zo laat de nieuwe glasvezeltechnologie toe alle kenmerken van de ADAMTS13-schaar op hetzelfde moment te beoordelen, wat een belangrijk tijdsvoordeel biedt ten opzichte van de huidige diagnostische technieken.

Analyse van de ADAMTS13-schaar

Om de diagnose van iTTP te bevestigen, evalueren de gespecialiseerde laboratoria tegenwoordig hoe actief de ADAMTS13-schaar nog kan knippen. Verder is het mogelijk de onderliggende oorzaak van de aandoening bij individuele iTTP-patiënten na te gaan door de aanwezigheid van antilichamen tegen de lichaamseigen ADAMTS13-schaar te controleren. Daarom is de ADAMTS13-schaar eerst aan een goud belegen optische vezel gekoppeld, waarna de glasvezel in het bloedstaal van een patiënt is ondergedompeld om alle eigenschappen van het schaarmolecule op te volgen. Na de geslaagde ontwikkeling van de verschillende diagnostische testen, zijn deze meteen afgesteld om in elk ziekenhuislaboratoria te kunnen gebruiken. Aangezien stalen van iTTP-patiënten succesvol van gezonde donoren zijn onderscheidden, zijn deze testen vervolgens goedgekeurd voor de diagnose van iTTP in een klinisch onderzoek.

De weg naar het ziekenhuis

Ondanks het feit dat gespecialiseerde laboratoria de diagnose van iTTP kunnen bevestigen, dringen artsen er op aan een makkelijke diagnose in elk ziekenhuis te kunnen formuleren. Dankzij de innovatieve glasvezeltechnologie zijn de diagnostische testen voor enkele kenmerken van de ADAMTS13-schaar in onderzoekslaboratoria ontwikkeld en gevalideerd. Daarnaast bieden de glasvezels ook perspectief voor de laatste test rond de activiteit van het schaarmolecule. Door de glasvezels met de verschillende testen samen te brengen tot één gecombineerde test, staat deze technologie klaar om zijn plaats binnen het ziekenhuis op te eisen. Terwijl de onderzoekslaboratoria beloftevolle resultaten naar buiten brengen, kijken artsen al uit naar deze nieuwe diagnose techniek en verwelkomen iTTP patiënten alle hulp met open armen. Je staat er waarschijnlijk niet bij stil, maar terwijl jij razend snel over het web surft, redden diezelfde optische glasvezels nu ook mensenlevens. Tijd om de spotlights meer dan eens opnieuw op de glasvezels te richten.

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Universiteit of Hogeschool
Master in de biochemie en de biotechnologie
Publicatiejaar
2020
Promotor(en)
Prof. Dr. Karen Vanhoorelbeke
Kernwoorden
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