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.

Kessel, A., Peri, R., Perricone, R., Guarino, M.d., Vadasz, Z., Novak, R., et al. (2012). The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 167(3), 422-428 [10.1111/j.1365-2249.2011.04527.x].

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

PERRICONE, ROBERTO;GUARINO, MARIA DOMENICA;
2012

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/16 - Reumatologia
English
Con Impact Factor ISI
Young Adult; Toll-Like Receptor 9; Complement C1 Inactivator Proteins; Humans; Autoimmunity; Aged; B-Lymphocytes; Lymphocyte Activation; Autoantibodies; Adult; Case-Control Studies; Immunologic Memory; Hereditary Angioedema Types I and II; Middle Aged; Signal Transduction; Female; Male
Kessel, A., Peri, R., Perricone, R., Guarino, M.d., Vadasz, Z., Novak, R., et al. (2012). The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 167(3), 422-428 [10.1111/j.1365-2249.2011.04527.x].
Kessel, A; Peri, R; Perricone, R; Guarino, Md; Vadasz, Z; Novak, R; Haj, T; Kivity, S; Toubi, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/77629
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