The Power of Pyrin
Researchers describe a new diagnostic tool for identifying familial Mediterranean fever
Inflammation, fever, and severe pain – a combination of these symptoms that could be ascribed to a wide range of conditions, which is why patients with familial Mediterranean fever (FMF) can remain undiagnosed for years. But despite the difficulty in identifying it, FMF remains the most common monogenic autoinflammatory disease in the world. That’s why scientists at VIB Leuven and Ghent University have collaborated to create a diagnostic tool to detect it (1). To find out more about the test, we spoke with Mohammed Lamkanfi, lead investigator and Professor at Ghent University.
What prompted you to investigate familial Mediterranean fever?
My lab has a longstanding interest in the mechanisms of inflammation, and in pathologies associated with defective innate immune signaling – particularly with regards to the inflammasomes. Pyrin, the protein mutated in FMF, triggers assembly of the inflammasomes and drives abnormal production of highly fever-inducing molecules (interleukins) that also cause tissue damage.
The causal gene of FMF has been known for almost 20 years, but it remained unclear how over 300 known causative mutations in the pyrin gene MEFV could trigger disease. Our studies clarified the molecular mechanism and led us to define an immunodiagnostic method that has been validated in 13 FMF patients so far.
How will the diagnostic affect patients?
The immunoassay requires a limited amount of blood, no sophisticated equipment, and gives results in a couple of hours. We think it will help reduce the current FMF diagnostic time – which I believe to be around five years – drastically, preventing unnecessary suffering, emergency care visits, and surgical procedures.
Timely diagnosis allows faster initiation of therapy – colchicine and anti-IL-1 drugs have proven efficacy in the condition – helping to prevent serious long-term complications like kidney failure.
How far are you from clinical trials – and what’s next?
The assay was tested in healthy controls as well as in patients suffering from FMF and two other unrelated autoinflammatory diseases. Our test specifically identified the FMF patients in those studies.
We are currently organizing a follow-up study involving larger cohorts of FMF patients and those suffering from other autoinflammatory diseases to validate the sensitivity and selectivity of the assay. If all goes well, we hope the test can be implemented in clinical diagnostic routines around the world in a year or so.
We will also continue studying the fundamental scientific mechanisms of inflammation responses in diseases with evidence of deregulated inflammasome signaling. Our ultimate goal is to advance understanding of the pathological mechanisms and to identify new targets that can be applied in diagnosis and therapy, so that as many patients can benefit as possible.
- H Von Gorp et al., “Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in pyrin inflammasome activation”, PNAS, [Epub ahead of print] (2016). PMID: 27911804.
My fascination with science, gaming, and writing led to my studying biology at university, while simultaneously working as an online games journalist. After university, I travelled across Europe, working on a novel and developing a game, before finding my way to Texere. As Associate Editor, I’m evolving my loves of science and writing, while continuing to pursue my passion for gaming and creative writing in a personal capacity.
