We studied the activity status phenotype, Toll-like receptor (TLR)-9 expression and total phosphotyrosine in B cells isolated from HAE patients. Additionally, the following autoantibodies were assessed in
the serum of 61 HAE patients: anti-nuclear, rheumatoid factor, anti-cardiolipin, anti-tissue transglutaminase, anti-endomysial, anti-Saccharomyces cerevisiae, anti-thyroid SCH772984 clinical trial and anti-neutrophil cytoplasmic antibodies. In 47·5% of HAE patients we detected at least one of the tested autoantibodies. Expression of CD69, CD5 and CD21 was found to be significantly higher on memory B cells from HAE patients compared to healthy controls (4·59 ± 4·41 versus 2·06 ± 1·81, P = 0·04, 8·22 ± 7·17 Tyrosine Kinase Inhibitor Library versus 3·65 ± 3·78, P = 0·05, 2·43 ± 0·54 versus 1·92 ± 0·41, P = 0·01, respectively). Total phosphotyrosine in B cells from HAE patients was significantly higher compared to healthy controls (4·8 ± 1·1 versus 2·7 ± 1·3, P = 0·0003). Memory B cells isolated from the HAE group contained higher amounts of TLR-9 compared to healthy controls (8·17 ± 4·1 versus 4·56 ± 1·6, P = 0·0027). Furthermore, the expression of TLR-9 in memory B cells from HAE patients with autoantibodies was significantly higher than
the control group (10 ± 4·7 versus 4·56 ± 1·6, P = 0·0002) and from that in HAE patients without autoantibodies (10 ± 4·7 versus 5·8 ± 0·9, P = 0·036). HAE patients have enhanced production of autoantibodies due most probably to the increased activation of B cells, which was found to be in association with a high expression of TLR-9.
Hereditary angioedema (HAE) is a rare autosomal dominant inherited disease characterized by recurrent attacks of subcutaneous or submucosal oedema typically involving the arms, legs, hands, feet, bowels, genitalia, trunk, face or upper airway. In most patients, this is the result of a quantitative (type I) or qualitative (type II) deficiency of the active C1-esterase inhibitor (C1-INH) [1]. C1-INH has an important regulatory role in the complement, kallikrein-kinin, fibrinolytic and coagulation systems. Its deficiency leads to a release of excessive vasoactive peptides, among which Glycogen branching enzyme bradykinin is considered to be most important in causing the development of angioedema [2,3]. Various immunoregulatory disorders have been described in patients suffering from HAE [4–10]. In an early study, 12% of the 157 HAE patients examined by Brickman et al. were found to have clinical immunoregulatory disorders, namely: glomerulonephritis (five patients), Sjögren’s syndrome (three patients), inflammatory bowel disease (three patients), thyroiditis (three patients), systemic lupus erythematosus (one patient), drug-induced lupus (one patient), rheumatoid arthritis (one patient), juvenile rheumatoid arthritis with immunoglobulin (Ig)A deficiency (one patient), incipient pernicious anaemia (one patient) and sicca syndrome (one patient) [11].