RT Journal Article
SR Electronic
T1 Blood-based test for diagnosis and functional subtyping of familial Mediterranean fever
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 960
OP 968
DO 10.1136/annrheumdis-2019-216701
VO 79
IS 7
A1 Hanne Van Gorp
A1 Linyan Huang
A1 Pedro Saavedra
A1 Marnik Vuylsteke
A1 Tomoko Asaoka
A1 Giusi Prencipe
A1 Antonella Insalaco
A1 Benson Ogunjimi
A1 Jerold Jeyaratnam
A1 Ilaria Cataldo
A1 Peggy Jacques
A1 Karim Vermaelen
A1 Melissa Dullaers
A1 Rik Joos
A1 Vito Sabato
A1 Alessandro Stella
A1 Joost Frenkel
A1 Fabrizio De Benedetti
A1 Joke Dehoorne
A1 Filomeen Haerynck
A1 Giuseppe Calamita
A1 Piero Portincasa
A1 Mohamed Lamkanfi
YR 2020
UL http://ard.bmj.com/content/79/7/960.abstract
AB Background and objective Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) worldwide. The disease is caused by mutations in the MEFV gene encoding the inflammasome sensor Pyrin. Clinical diagnosis of FMF is complicated by overlap in symptoms with other diseases, and interpretation of genetic testing is confounded by the lack of a clear genotype–phenotype association for most of the 340 reported MEFV variants. In this study, the authors designed a functional assay and evaluated its potential in supporting FMF diagnosis.Methods Peripheral blood mononuclear cells (PBMCs) were obtained from patients with Pyrin-associated autoinflammation with an FMF phenotype (n=43) or with autoinflammatory features not compatible with FMF (n=8), 10 asymptomatic carriers and 48 healthy donors. Sera were obtained from patients with distinct AIDs (n=10), and whole blood from a subset of patients and controls. The clinical, demographic, molecular genetic factors and other characteristics of the patient population were assessed for their impact on the diagnostic test read-out. Interleukin (IL)-1β and IL-18 levels were measured by Luminex assay.Results The ex vivo colchicine assay may be performed on whole blood or PBMC. The functional assay robustly segregated patients with FMF from healthy controls and patients with related clinical disorders. The diagnostic test distinguished patients with classical FMF mutations (M694V, M694I, M680I, R761H) from patients with other MEFV mutations and variants (K695R, P369S, R202Q, E148Q) that are considered benign or of uncertain clinical significance.Conclusion The ex vivo colchicine assay may support diagnosis of FMF and functional subtyping of Pyrin-associated autoinflammation.