Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations

Abstract

Objective: To prospectively monitor inflammatory activity over a prolonged period in a cohort of Turkish patients with FMF, their healthy relatives and healthy controls and to relate this to their MEFV genotypes.

Methods: 43 patients with FMF and 75 of their asymptomatic relatives underwent fortnightly assessments and venesection for measurement of CRP and SAA over 5 months. 50 unrelated healthy population matched controls were also studied. MEFV genotyping was performed on all participants and comparisons were made between the different groups.

Results: Paired MEFV mutations were detected in 84% of FMF patients and single mutations in 12%. Substantial acute phase reactivity was seen among the patients with FMF during attacks (median SAA 693 mg/l, CRP 115 mg/l). Between attacks there was also some inflammatory activity (median SAA 6 mg/l, CRP 4 mg/l). Among healthy controls 16% were heterozygotes for MEFV mutations and 4% had two mutations. As expected there was a substantial carrier rate among healthy relatives with mutations detected in almost 92%. Asymptomatic MEFV heterozygotes had elevated acute phase proteins compared to wild type subjects.

Conclusion: Substantial sub-clinical inflammation occurs widely and over prolonged periods in patients with FMF, indicating that the relatively infrequent clinically overt attacks represent the 'tip of the iceberg' in this disorder. Both basal and peak acute phase protein concentrations were greater in MEFV heterozygotes than in wild-type controls, regardless of mutation demonstrating a 'pro-inflammatory' phenotype among FMF carriers. Upregulation of the acute phase response among carriers of FMF may augment their innate host response and contribute to better resistance to infection.