Skin test detects prion infection before symptoms appear
Researchers have developed a method of using skin samples to diagnose prion infections – even before they establish themselves…
An international team of researchers successfully have used two methods to detect prions in skin samples collected from inoculated rodents.
Prions are able to infect both animals and humans, and often go undetected as they destroy brain tissue, causing memory loss, mobility issues, and ultimately death. In humans, prions cause Creutzfeldt-Jakob disease (CJD), a fatal degenerative brain disorder, and other progressive neurodegenerative conditions.
Preclinical detection of prions is currently difficult, however recent research has shown that skin samples hold early signs of prion disease that precede neurologic symptoms.
“Currently a definitive diagnosis of Creutzfeldt-Jakob disease is dependent on the examination of diseased brain tissue obtained at biopsy or autopsy. It has been impossible to detect at the early preclinical stage,” said Dr Wenquan Zou, Associate Professor of Pathology at Case Western Reserve University School of Medicine.
Prof Zou and colleagues were able to successfully detect prions in rodent skin samples as early as two weeks after infection, and before they showed any clinical signs of prion disease. They were also able to detect prions in the skin of uninoculated rodents that were housed alongside inoculated rodents in the same cage. Thus, they demonstrated that prion transmission can occur between cohabiting rodents.
The researchers suggest that skin prions could be used as a useful biomarker for the preclinical diagnosis of prion diseases.
During the study two detection methods were compared: RT-QuIC (real-time quaking-induced conversion) and sPMCA (serial protein misfolding cyclic amplification).
“Both assays were able to efficiently amplify trace amounts of disease-associated prion protein found in the skin tissues of infected animals,” said the study’s first author Zerui Wang, a PhD student from the First Hospital of Jilin University, China, working in the Zou laboratory.
RT-QuIC has previously been used to detect prion particles in symptomatic CJD patients, but it requires invasive cerebrospinal fluid (CSF) samples.
“The CSF-based prion test results could be uncertain in some cases and not all CSF specimens from patients with prion disease are RT-QuIC positive,” said Dr Qingzhong Kong, Associate Professor of Pathology at Case Western Reserve University School of Medicine and co-corresponding author on the study. “Although skin samples may not replace CSF in routine RT-QuIC-based prion disease diagnosis, they may be helpful when prion disease is suspected but CSF is either unavailable or RT-QuIC-negative.”
Prof Zou mentioned how the skin is readily accessible, and with skin biopsies being minimally invasive, “detection of skin prions will be very useful for monitoring disease progression and assessing therapeutic efficacy during clinical trials or treatments when prion therapy becomes available in the future.”
The team were awarded a $2.9 million grant from the National Institutes of Health to validate their methods using human skin samples to determine if skin prions could serve as a diagnostic biomarker for CJD.
The study was published in the journal Nature Communications.