BRIEF REPORT The role of regulatory T cells in familial Mediterranean fever (FMF) D. Rimar & I. Rosner & G. Slobodin & N. Boulman & E. Toubi & A. Kessel & R. Peri & M. Rozenbaum Received: 27 June 2011 /Revised: 5 December 2011 /Accepted: 23 December 2011 /Published online: 11 January 2012 # Clinical Rheumatology 2012 Abstract The role of regulatory T cells (T-regs) in familial Mediterranean fever (FMF) was never evaluated. Prelimi- nary studies that we have conducted suggested a rise in the number of regulatory T cells after FMF attacks reaching a maximal level at 7 days. The aim of this study was to evaluate the percentage and activity of regulatory T cells in FMF. Six patients with refractory FMF and six healthy controls were evaluated. The percentage of T-reg cells and forkhead box protein 3 (Foxp3) expression was evaluated and compared between four states: FMF in remission, FMF at the first day of an attack, FMF 7 days after the start of the attack, and healthy controls. Four females and two males were included. All patients had FMF with high severity score, 2.8±0.4 (0–3). The mean age was 31.6±6.2. The mean age at onset was 9.3±9.3. The mean colchicine dose was 2.6 mg±0.4. The expression of Foxp3 7 days after the attacks was significantly higher than in FMF at the first day of the attack, FMF in remission, and healthy controls 10.08±2.36 vs. 7.005±0.3 vs. 5.3±1.06 vs. 4.44±1.8; p <0.05 (Fig. 1). The percentage of T-regs in peripheral blood was not statistically different between the four groups. Theexpression of Foxp3 by T-regs increases 7 days after attacks of FMF. Anti-inflammatory cytokines interleukin- 10 and TGF-β are known to activate T-regs and have been reported to increase in FMF attacks in line with the present findings. It is suggested that T-regs may have a role in terminating FMF attacks. Keywords Familial Mediterranean fever . FMF . Foxp3 . Regulatory T cells . T-regs Introduction Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, and erysipelas-like skin lesions. In some cases, it is complicated by secondary amyloidosis progressing to renal failure [1]. Mutations in the Mediterranean fever gene (MEFV), mapped to the short arm of chromosome 16, encoding the pyrin/marenostrin protein, are strongly associated with clin- ical FMF and felt to be pathogenic [2, 3]. Pyrin is thought to regulate caspase 1 function indirectly, thereby influencing interleukin (IL)-1β processing and apoptosis [2]. By current understanding, a defective pyrin protein may be responsible for an exaggerated FMF inflammatory response mediated by IL-1 and a cascade of proinflammatory cytokines. Indeed proinflammatory cytokines such as IL-6, IL-8, IL-12, and tumor necrosis factor (TNF) alpha are elevated in FMF patients during attacks [4]. Recently, some authors have noted that on top of simple Th1 polarization, in FMF, there are also evident increases in concentrations of the anti inflammatory cytokines IL-10 and transforming growth factor (TGF)-β, both known to induce T-regs expression, suggesting a more complex picture of events [5, 6]. T-regs serve to control inflammation and play an important role in autoimmune pathogenesis by maintain- ing self-tolerance and controlling expansion and activation of autoreactive CD4+ T effector cells [7]. T-regs can be D. Rimar (*) : I. Rosner : G. Slobodin : N. Boulman : M. Rozenbaum Rheumatology Unit, Bnai Zion Medical Center, POB 4940, Haifa 31048, Israel e-mail: doronrimar@gmail.com E. Toubi : A. Kessel : R. Peri Immunology Unit, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel Clin Rheumatol (2012) 31:885–888 DOI 10.1007/s10067-011-1935-7