RESUMEN
Autoinflammatory attacks in familial Mediterranean fever (FMF) are accompanied by elevated levels of interleukin-6 (IL-6), and are controllable by IL-1-targeting drugs. In combination, IL-6 and IL-1 are known to be potent inducers of T helper (Th) 17 cells development. Therefore, we studied the Th17 population size, and activation potential, of FMF patients. Based on the relative mRNA expression of the Th1, Th2, Treg and Th17 transcription factors T-bet, GATA3, FOXP3 and retinoic acid-related orphan receptor γT (RORγT), respectively, the Th17 population in peripheral blood mononuclear cells (PBMCs) of healthy subjects was estimated at 2.5% of the entire Th population and 4.4% in FMF patients in remission (n=6 for each group, P=0.03). IL-17 secretion after universal stimulation of the T-cell receptor in PBMCs culture was twice higher in cultures of patients with frequent attacks (n=18) than in those of patients with infrequent attacks (n=10, 1124±266 vs 615±196 pg ml(-1), P=0.009). IL-17 secretion correlated well with IL17A mRNA level. Part of the increased secretion was related to the deleterious, MEFV p.M694V homozygous genotype (n=19, 1.5-fold, P=0.03). Almost all IL-17 producer cells were CD4-positive (CD4(+)IL-17(+)). In conclusion, frequent attacks and the deleterious FMF genotype appear to drive FMF patients to a heightened Th17 response.
Asunto(s)
Fiebre Mediterránea Familiar/inmunología , Células Th17/inmunología , Adolescente , Adulto , Estudios de Casos y Controles , Células Cultivadas , Proteínas del Citoesqueleto/genética , Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/metabolismo , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Pirina , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: 'Erysipelas-like' erythema (ELE) is a well recognized, although uncommon, manifestation of familial Mediterranean fever (FMF), which is frequently mistaken for infectious erysipelas, especially when forming the initial disease presentation. AIM: To clinically and genetically characterize ELE as the first manifestation of FMF. METHODS: FMF patients with ELE as the first disease presentation (study group), were compared with FMF patients with ELE, appearing during the disease course (control group I), and to those FMF patients who never had ELE (control group II). RESULTS: Patients of the study group were comparable to patients without ELE with respect to all demographic, clinical and genetic features studied, and yet differed from patients with ELE appearing later in the disease course in disease severity score (1.7 ± 0.4 vs. 2.4 ± 0.6, P = 0.01), length of diagnosis delay (7.2 ± 6.4 vs. 2.3 ± 3.3 years, P=0.037), age of FMF onset (24.8 ± 19.9 vs. 5.6 ± 5.7 years of age, P=0.014) and rate of homozygosity to the M694V mutation (14.3% vs. 68.7% respectively). ELE traits in the study and control groups were alike. CONCLUSIONS: FMF with ELE as the first disease manifestation form an uncommon subgroup, clinically and genetically diverging from the rest of the FMF-ELE patients.
Asunto(s)
Eritema/etiología , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico , Adolescente , Niño , Erisipela , Eritema/genética , Fiebre Mediterránea Familiar/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, presenting with recurrent episodes of fever and polyserositis. Neurologic involvement in FMF is rare and usually considered fortuitous. The aim of this article is to review the spectrum of possible neurologic manifestations, which can be encountered in FMF patients, and to establish their relation to FMF. METHODS: We reviewed the literature based on Pubmed search to find neurologic manifestations, which were reported in FMF patients. To that we added our own experience on the subject, abstracted from our computerised FMF registry of 12000 FMF patients of the National FMF Center and the computerised database of Sheba Medical Center. RESULTS: A wide range of neurologic manifestations involving FMF patients was noted. A large part of these manifestations could be directly related to FMF, its complications, associated diseases and treatment adverse effects. The remaining were incidental, or of uncertain association to FMF. CONCLUSION: A physician, taking care of an FMF patient, can face various neurologic manifestations and should be aware of their origin. The current chapter provides an insight to this association of FMF.