José A Martínez-Flores1, Manuel Serrano1, Dolores Pérez1, David Lora2, Estela Paz-Artal3, José M Morales1, Antonio Serrano4. 1. Department of Immunology, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain. 2. Epidemiology Section, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Department of Immunology, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain; Immunology Section, Universidad San Pablo-CEU, Madrid, Spain. 4. Department of Immunology, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain; Immunology Section, Universidad San Pablo-CEU, Madrid, Spain. Electronic address: aserrano@h12o.es.
Abstract
BACKGROUND: Patients with antiphospholipid syndrome (APS) have a hypercoagulable condition associated with the presence of antiphospholipid autoantibodies (aPL). Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2 glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection assays are mainly based on interaction with complement and are not appropriate to detect B2A-CIC because IgA does not fix complement using the classical pathway. PATIENTS AND METHODS: Sera from healthy blood donors (N= 247) and from patients with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were studied in a case-control study. Two methods were applied, these being a capture ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI after dissociating CIC. RESULTS: B2A-CIC values in APS-patients were 19.27 ± 2.6 AU vs 6.1 ± 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001). Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 ± 10.8 IU/mL in patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI and autoantibodies IgA aB2GPI serum levels. CONCLUSION: B2A-CIC can be identified and quantified in an easy and reproducible manner using two complement-independent methods. The use of these tests in prospective studies will allow better understanding of the prognosis and outcome of patients.
BACKGROUND:Patients with antiphospholipid syndrome (APS) have a hypercoagulable condition associated with the presence of antiphospholipid autoantibodies (aPL). Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2 glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection assays are mainly based on interaction with complement and are not appropriate to detect B2A-CIC because IgA does not fix complement using the classical pathway. PATIENTS AND METHODS: Sera from healthy blood donors (N= 247) and from patients with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were studied in a case-control study. Two methods were applied, these being a capture ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI after dissociating CIC. RESULTS: B2A-CIC values in APS-patients were 19.27 ± 2.6 AU vs 6.1 ± 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001). Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 ± 10.8 IU/mL in patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI and autoantibodies IgA aB2GPI serum levels. CONCLUSION: B2A-CIC can be identified and quantified in an easy and reproducible manner using two complement-independent methods. The use of these tests in prospective studies will allow better understanding of the prognosis and outcome of patients.
Authors: Manuel Serrano; Laura Morán; Jose Angel Martinez-Flores; Esther Mancebo; Daniel Pleguezuelo; Oscar Cabrera-Marante; Juan Delgado; Antonio Serrano Journal: Front Immunol Date: 2019-12-23 Impact factor: 7.561
Authors: Oscar Cabrera-Marante; Edgard Rodríguez de Frías; Manuel Serrano; Fernando Lozano Morillo; Laura Naranjo; Francisco J Gil-Etayo; Estela Paz-Artal; Daniel E Pleguezuelo; Antonio Serrano Journal: Int J Mol Sci Date: 2020-11-26 Impact factor: 5.923
Authors: José A Martínez-Flores; Manuel Serrano; Dolores Pérez; Gómez de la Cámara A; David Lora; Luis Morillas; Rosa Ayala; Estela Paz-Artal; José M Morales; Antonio Serrano Journal: J Atheroscler Thromb Date: 2016-04-11 Impact factor: 4.928