title: The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency.
abstract: Patients with hereditary angioedema (HAE) tend to produce autoantibodies and have a propensity to develop immunoregulatory disorders. We characterize the profile of autoantibodies in a group of HAE patients and investigate their memory B cells' phenotype and activation status. 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 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 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.
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel. aharon.kessel@b-zion.org.il
authors.forename: A
authors.initials: A
authors.lastname: Kessel
authors.forename: R
authors.initials: R
authors.lastname: Peri
authors.forename: R
authors.initials: R
authors.lastname: Perricone
authors.forename: M D
authors.initials: MD
authors.lastname: Guarino
authors.forename: Z
authors.initials: Z
authors.lastname: Vadasz
authors.forename: R
authors.initials: R
authors.lastname: Novak
authors.forename: T
authors.initials: T
authors.lastname: Haj
authors.forename: S
authors.initials: S
authors.lastname: Kivity
authors.forename: E
authors.initials: E
authors.lastname: Toubi
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D016022:Case-Control Studies; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency*; D050718:Complement C1 Inhibitor Protein; D005260:Female; D056829:Hereditary Angioedema Types I and II / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9