title: β2-Glycoprotein I/IgA Immune Complexes: A Marker to Predict Thrombosis After Renal Transplantation in Patients With Antiphospholipid Antibodies.
abstract: Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to β2-glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers.
  
  
  
  We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-β2-glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months.
  
  
  
  In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 (P<0.001) and 8.6% in the control group (P<0.001). The incidence of graft thrombosis in group 1 (31.2%) was significantly higher than that observed in group 2 (3.3%,P<0.001) and the control group (2.6%,P<0.001). In a multivariate analysis, the presence of B2A-CIC was an independent variable to experience any type of posttransplant thrombosis (hazard ratio, 6.72; 95% confidence interval, 4.81-9.37) and, prominently, for graft thrombosis (hazard ratio, 14.75; 95% confidence interval, 9.11-23.89). No significant differences were found between B2A-CIC-negative and control group patients.
  
  
  
  The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC-negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC-positive patients.
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: José A
authors.initials: JA
authors.lastname: Martínez-Flores
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Florencio
authors.initials: F
authors.lastname: García
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Oscar
authors.initials: O
authors.lastname: Cabrera-Marante
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Pleguezuelo
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: José M
authors.initials: JM
authors.lastname: Morales
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.).
authors.forename: Esther
authors.initials: E
authors.lastname: González
authors.affiliation: From Department of Immunology (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.), and Department of Nephrology (F.G., E.G.), Instituto de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain (M.S., J.A.M.-F., D. Pérez, O.C., D. Pleguezuelo, E.P.-A., J.M.M., A.S.); Facultad de Medicina, Universidad Complutense de Madrid, Spain (M.S., E.P.-A.). aserrano@h12o.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Serrano
mesh_terms: D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000639:trends; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013927:Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D053482:beta 2-Glycoprotein I / Q000097:blood*
chemical_list: D017152:Antibodies, Antiphospholipid; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D053482:beta 2-Glycoprotein I
keywords: antibodies, antiphospholipid; autoantibodies; graft occlusion, vascular; immune complex diseases; kidney transplantation; thrombosis