Have you ever heard of diseases that cause problems with the immune system? They’re called autoinflammatory diseases, and they cause cells that are supposed to protect the body from outside bacteria and viruses to attack your own body by mistake! One of the most common of these diseases is Familial Mediterranean Fever (FMF). FMF is monogenic, meaning it is controlled by only one gene. Unfortunately, as with most autoinflammatory disease, FMF is extremely difficult to diagnose mainly because its symptoms are similar to so many other conditions.

researcher examining assay

Photo obtained from Flickr

Geneticists have been able to determine that FMF is caused by mutations, or genetic differences, in the MEFV gene. This gene codes for a sensor of a complex of proteins called an inflammasome. Inflammasomes serve as danger signals that let the immune system know when foreign molecules such as viruses are present in the body. The specific inflammasome sensor that this disease stems from is called Pyrin. Although genetic tests are able to pick out these mutations in the MEFV gene, diagnosing FMF is a bit more complicated because there are over 340 different versions of the gene and many of these versions don’t have a clear association with a specific phenotype, a visible trait that results from a gene.
A paper published in April of 2020 shows the extraordinary results that can come from combing clinical and genetic knowledge.

A group of scientists from Belgium, China, Italy and the Netherlands were able to develop an assay that has the potential to improve the diagnostic capability for FMF.

This test involved taking three different kinds of samples from patients. The first were peripheral blood mononuclear cells (PBMCs) which are blood cells that have a round nucleus; in humans these blood cells consist mainly of lymphocytes which are better known as B cells and T cells. These samples were taken from patients who had autoinflammation that was associated with the Pyrin sensor mentioned previously. The patients either had FMF, had autoinflammatory symptoms that are not known to be related to FMF, were carriers who did not experience FMF symptoms, or healthy donors which served as the control group. The second sample was blood serum taken from patients who had distinct autoinflammatory diseases. The third was a regular “whole” blood sample taken from small groups of both the patients and controls (healthy donors). There was also an assessment of clinical, demographic, and molecular genetic factors to determine their impacts on the diagnostic results.

This assay yielded excellent results. It was able to differentiate FMF patients from the controls and from patients with related clinical disorders. That is a huge solution to the problems experienced through clinical diagnosis! On the genetics end, the test was also able to separate the patients who had known FMF mutations from those who had other mutations in the MEFV gene that are not considered to be FMF related. As with all new methods, this assay will have to be tested and retested to make sure these results were significant. But for now, we can have faith that this test has real potential to help people who are struggling to get a diagnosis of FMF!

Van Gorp H, Huang L, Saavedra P, et al (2020). Blood-based test for diagnosis and functional subtyping of familial Mediterranean fever. doi: 10.1136/annrheumdis-2019-216701