OPEN Research Support

Sussi Bagge Mortensen
Department of Clinical Immunology, Odense University Hospital

Projekt styring
Projekt status    Sampling ongoing
Data indsamlingsdatoer
Start 01.05.2017  
Slut 30.04.2020  

Familial Mediterranean Fever in Denmark: new insights into epidemiology and molecular mechanisms of pathogenesis

Short summary


Familiar Mediterranean fever (FMF) is an auto-inflammatory disorder which mainly affects people of Mediterranean origin.  It is characterized by periodic attacks of fever, accompanied by joint- and abdominal pain as well as skin lesions. It is caused by mutations in the MEFV gene, which encodes a protein involved in a complex regulation of the innate immune system, by regulating inflammation.  However, its exact role in this regulation is not fully understood, and the question of how exactly mutations in the MEFV gene leads to disease, is yet to be answered. 

The prevalence of FMF in Denmark has never been studied and in general there is a lack of knowledge regarding treatment strategies, complications and co-morbidities. Improper- or untreated FMF patients are in risk of developing kidney failure, atherosclerosis and coronary heart disease, thus effective diagnosis and treatment is of great importance.

Aims and objectives:

We wish to explore the molecular mechanisms of MEFV involvement in inflammation, thereby gaining insights into the pathogenesis of FMF. Furthermore we wish to establish the first Danish FMF cohort and biobank as a tool for the current and future studies of FMF.


Familial Mediterranean Fever (FMF) is a systemic auto-inflammatory disorder characterized by recurrent self-limiting episodes of fever usually lasting between 1-3 days. The attacks are accompanied by serositis, arthritis, myalgia, skin lesions and abdominal pain due to peritonitis. The localized inflammation in FMF patients are caused by a massive influx of polymorphonuclear leukocytes into the affected tissue.

In roughly 30% of FMF patients, inflammation also persists in between attacks, and in another fraction, subclinical markers of inflammation is the only manifestation of disease.

The most significant form of complication is secondary amyloidosis, potentially leading to renal insufficiencies and neuropathy, thus being the main cause of excess mortality in FMF patients.  FMF mainly affects ethnic groups around the Mediterranean basin; Turks, Sephardic Jews, Armenians and Arabs, and to a lesser extend people of Italian and Greek origin. The clinical manifestations are very heterogeneous among FMF patients and are to some extent coupled to the mutational genotype. However, heterozygous carrier rates are high in the mentioned ethnic groups and some carriers of just one mutated allele presents with milder forms of FMF, thus challenging the dogma of autosomal recessive inheritance.

Daily colchicine treatment can reduce the number and intensity of attacks, and prevent late complications by reducing Serum Amyloid A levels. Some FMF patients do not respond to colchicine treatment, and in these cases IL1 beta blockade has proven to be a useful adjunctive therapy.

The prevalence of FMF in Denmark has never been investigated, and there is a lack of knowledge regarding the success of treatment strategies, nature and extent of complications and co-morbidities etc. in the Danish FMF patients. The chronic inflammation predisposes FMF patients to infertility, atherosclerosis and coronary heart disease, thus awareness of, and knowledge about treatment strategies that tightly control the levels of subclinical inflammation through regulation of colchicine dose, is of great importance.

Of equal importance is the optimization of the diagnosis of FMF. The overlapping clinical manifestations of the MAIS syndromes, along with the heterogeneity of genotype/phenotype relationships, call for investigation of other possible factors contributing to the FMF phenotype. Likewise, searching for other possible causes of FMF in patients without a detected mutation could improve our knowledge of FMF pathogenesis, and in the end, improve the interplay of clinical and molecular diagnostics of FMF.


Description of the cohort

Adult FMF patients (men and women) attending the clinics of infectious disease at Odense University Hospital, Hvidovre Hospital, Roskilde Hospital, Rigshospitalet and Skejby University Hospital will be asked to participate in the project. 

Data and biological material

Blood samples for RNA- and DNA extraction, isolation of PBMCs and serum fractionation will be collected from all included patients.

Data regarding ethnicity, clinical manifestations, treatment, prior genetic testing, family history of FMF and lab results from measuring of inflammatory parameters will be obtained during project enrolment.

Collaborating researchers and departments

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet

  • Professor Jens Lundgren, MD, DMSc

Department of Infectious Diseases, Hvidovre University Hospital

  • Senior consultant Ann-Brit Eg Hansen, MD, PhD
Department of Infectious Diseases, Skejby University Hospital 

  • Senior consultant and Assistant professor Carsten Schade Larsen, MD, DMSc

Department of Clinical Genetics, Sygehus Lillebælt, Vejle

  • Senior consultant and Assistant professor Anders Bojesen, MD, PhD

Department of Medicin, Zealand University Hospital, Roskilde

  • Head of Section of Infectious Diseases and Senior consultant Nina Friis-Møller, PhD, DMSc