The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency

• Published in: Clinical and experimental immunology Vol. 167; no. 3; pp. 422 - 428
• Main Authors: Kessel, A., Peri, R., Perricone, R., Guarino, M. D., Vadasz, Z., Novak, R., Haj, T., Kivity, S., Toubi, E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2012; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Allergic diseases; Analytical, structural and metabolic biochemistry; autoantibodies; Autoantibodies - blood; Autoimmunity; B cells; B-Lymphocytes - classification; B-Lymphocytes - immunology; Biological and medical sciences; Case-Control Studies; Complement C1 Inactivator Proteins - deficiency; Complement C1 Inhibitor Protein; Female; Fundamental and applied biological sciences. Psychology; hereditary angioedema; Hereditary Angioedema Types I and II - etiology; Hereditary Angioedema Types I and II - immunology; Humans; Immunologic Memory; Immunopathology; Lymphocyte Activation; Male; Medical sciences; Middle Aged; Signal Transduction - immunology; Skin allergic diseases. Stinging insect allergies; TLR‐9; Toll-Like Receptor 9 - metabolism; total phosphotyrosine; Translational Studies; Young Adult; Autoimmunity; Allergy; Immunopathology; Skin disease; Complement C1; Antibody; TLR-9; Deficiency; Autoantibody; Biochemistry; B-Lymphocyte; B cells; Hereditary; Toll like receptor 9; hereditary angioedema; Angioneurotic edema; total phosphotyrosine; Inhibitor; autoantibodies
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04527.x

Summary
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.