A novel cluster of patients with Familial Mediterranean Fever (FMF) in southern Italy

Bonfrate, Leonilde; Scaccianoce, Giuseppe; Palasciano, Giuseppe; Ben-Chétrit, Eldad; Portincasa, Piero

doi:10.1111/eci.12783

Cited by 21 publications

(23 citation statements)

References 17 publications

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“…The predominance of high-penetrance MEFV mutations in our German cohort is consistent with previous reports on patients with FMF with the Turkish-Armenian ancestry. A recent report from south Italy has described an endemic area for a mild-to-moderate FMF variant with predominant E148Q and R761H MEFV mutations ( 32 ), which were not observed in our cohort.…”

Section: Discussioncontrasting

confidence: 62%

IL1-blocking therapy in colchicine-resistant familial Mediterranean fever

2018

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ObjectiveApproximately 10%–20% of patients with familial Mediterranean fever (FMF) show an inadequate response to colchicine. In our cohort study, patients with FMF with or without amyloidosis and with an inadequate response to colchicine were treated with anakinra or canakinumab.MethodsClinical and laboratory parameters, Mediterranean fever (MEFV) mutations, and patient-reported outcomes were analyzed in 31 patients treated with anakinra or canakinumab.ResultsIn a cohort of 250 adult patients with FMF, 31 patients were treated with anakinra (n=29) or canakinumab (n=2). The median Pras FMF severity score was 8 (range, 5–14) and correlated with the presence of high-penetrance MEFV mutations (p.Met-694-Val or p.Met-680-Ile). The FMF severity score was 11 in patients with two high-penetrance MEFV mutations (68%), 9 in those with a single high-penetrance MEFV mutation (19%), and 7.5 in those without high-penetrance MEFV mutations (13%, p=0.2). FMF-related amyloid A amyloidosis was diagnosed in 12 (39%) patients. Anakinra was used daily in 20 patients, thrice a week in 7, and upon demand during attacks in 2. Two patients were treated with canakinumab. IL-1-blocking treatment showed a rapid (2±3 days) and persistent suppression of FMF symptoms and inflammatory parameters. The frequency of FMF attacks was significantly reduced (p<0.003). Both patient- and physician-reported FMF activity significantly improved (p<0.0001).ConclusionIL-1-blocking therapy was well tolerated over a median period of 2 years and reduced the frequency of FMF attacks in patients with colchicine-resistant FMF.

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Section: Discussioncontrasting

confidence: 62%

IL1-blocking therapy in colchicine-resistant familial Mediterranean fever

2018

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“…Both the E148Q and R761H variants are usually considered low penetrance alleles, although they have been associated with FMF in patients from a recently described novel endemic area in southeastern Italy. 50 Interestingly, patients with compound heterozygous E148Q-R761H alleles responded similarly to patients with disease-penetrant FMF mutations in the ex vivo colchicine test. Given that E148Q does not cause FMF as discussed above, we conclude that the R761H mutation renders Pyrin activation independent of microtubule dynamics, similarly to the disease-penetrant FMF mutations M680I, M694V and M694I.…”

Section: Discussionmentioning

confidence: 95%

Blood-based test for diagnosis and functional subtyping of familial Mediterranean fever

et al. 2020

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Background and objectiveFamilial 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.MethodsPeripheral 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.ResultsThe 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.ConclusionThe ex vivo colchicine assay may support diagnosis of FMF and functional subtyping of Pyrin-associated autoinflammation.

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“…Statements Other n = 1 62 The Apulia region represents a new endemic area for familial Mediterranean fever (FMF). Clinical presentation of FMF can be misleading and requires a complete and early workup to recognise the disease and avoid unjustified surgery.…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…We recently described a novel cluster of patients with FMF and suggested that the Apulia region in southern Italy represents a new endemic area for familial Mediterranean fever (FMF). The compound heterozygosity for MEFV variants E148Q/R761H was largely prevalent in our population.…”

Section: A Novel Cluster Of Patients With Familial Mediterranean Fevementioning

confidence: 99%