These included a T cell subpopulation shift and an evidence for polyclonal B cell activation and high levels of circulating immune complexes [12]. Recently, Farkas et al. assessed the clinical data and immunoserological parameters of 130 Hungarian HAE patients. In agreement with the

above early study, 12% were found to suffer from immunoregulatory disorders and in addition the authors revealed the presence of autoantibodies in 47·7% of their HAE patients. Interestingly, increased production of autoantibodies, especially anti-nuclear antibodies, was also found in a control group of patients with non-C1 INH-deficient angioedema [13]. The aim of this study was to characterize the autoantibody profile in a large find more group of HAE patients. Furthermore, we analysed the phenotype, including Toll-like receptor (TLR)-9 expression and activation status of memory B cells isolated from patients with HAE, aiming to propose a possible mechanism for this B cell autoreactivity. We studied 61 patients with C1-INH deficiency

36 women and 25 men aged 43·3 ± 14 [mean ± standard deviation (s.d.) years, range 19–70 years]. Fifty-six had type 1 HAE and five had type 2 HAE. The diagnosis of HAE was based on the patient’s family history, clinical Mitomycin C presentation and laboratory results of levels of functional or antigenic C1 esterase inhibitor of less than half the normal levels. The patients were recruited from Israel (30 patients, 15 women, 15 men) and Italy (31 patients, Teicoplanin 21 women, 10 men). Thirty-seven of 61 (60%) patients were treated with

danazol. Seventy healthy age- and sex-matched volunteers from the medical staff of our medical centre served as controls. Twenty controls were used for the B cell phenotype and activation profiles and 50 controls were used for the analysis of serum autoantibodies. The controls were healthy by self-report, with no clinical symptoms of autoimmune or infectious diseases. The local Committee on Human Experimentation approved the study. Blood samples were drawn from HAE patients during their visits in the out-patient clinic and the serum was stored at –20°C until assayed. The detection of anti-nuclear antibodies (ANA) in the patients’ serum was assayed by indirect immunofluorescence using slides covered with HEp-2 cells (Zeus Scientific, Inc., Branchburg, NJ, USA). Anti- extractable nuclear antigen (ENA) antibodies were analysed using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Orgentec Diagnostika GmbH, Mainz, Germany). Rheumatoid factor was assayed by the 2-min latex slide test (Biokit, SA, Barcelona, Spain). Anti-cardiolipin antibodies were analysed using a commercial ELISA kit (Genesis Diagnostics, Cambridgeshire, UK). Antibodies to tissue transglutaminase (ttG) were analysed using a commercial ELISA kit (Inova Diagnostics, Inc., San Diego, CA, USA) Anti-endomysial antibodies were analysed using a commercial ELISA kit (Inova Diagnostics, Inc.