title: Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.
abstract: BACKGROUND
  New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections.
  
  
  METHODS
  We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection.
  
  
  RESULTS
  During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection.
  
  
  CONCLUSIONS
  Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sarmiento
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Calahorra
authors.affiliation: Cardiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Yañez
authors.affiliation: Cardiology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gomez-Sanchez
authors.affiliation: Cardiology Department, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Crespo-Leiro
authors.affiliation: Cardiology Department, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Paniagua
authors.affiliation: Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.affiliation: Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Cebrian
authors.affiliation: Heart Surgery Department, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Rabago
authors.affiliation: Heart Surgery Department, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Beltran
authors.initials: B
authors.lastname: Levy
authors.affiliation: Heart Failure and Cardiomyopathy Unit, Heart Failure and Heart Transplant Section, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Segovia
authors.affiliation: Heart Failure and Cardiomyopathy Unit, Heart Failure and Heart Transplant Section, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gomez-Bueno
authors.affiliation: Heart Failure and Heart Transplant Unit, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Lopez
authors.affiliation: Cardiology Department, Sant Pau Hospital, Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mirabet
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Navarro
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Rodriguez-Molina
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Cruz
authors.affiliation: Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain. Electronic address: javier.carbone@salud.madrid.org.
authors.forename: Javier
authors.initials: J
authors.lastname: Carbone
mesh_terms: D000328:Adult; D053264:B-Cell Activating Factor / Q000097:blood; D001424:Bacterial Infections / Q000453:epidemiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology*; D007136:Immunoglobulins / Q000097:blood* / Q000276:immunology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D013030:Spain; D014777:Virus Diseases / Q000453:epidemiology / Q000503:physiopathology
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D007136:Immunoglobulins
keywords: complement; heart transplantation; hypogammaglobulinemia; infection; risk factors