title: Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.
abstract: BACKGROUND
  Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG.
  
  
  METHODS
  Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited. Patients received IVIG (Flebogamma 5%), as follows: 2 doses of 200 mg/kg followed by up to 5 additional doses of 300 mg/kg to maintain IgG >750 mg/dL. IgG and specific antibody titers to distinct microorganisms were tested during follow-up. The primary outcome measure was development of severe infection during the study period. Data on the primary outcome were matched with those of 13 recipients with post-transplant HGG who were not included in the clinical trial and with those of 11 recipients who did not develop HGG during the same study period.
  
  
  RESULTS
  Mean time to detection of HGG was 15 days. IgG and specific antibody reconstitution (anti-cytomegalovirus, anti-Haemophilus influenza, and anti-hepatitis B surface antigen antibodies) was observed in IVIG-treated patients. Severe infection was detected in 3 of 12 (25%) IVIG-treated recipients, in 10 of 13 (77%) HGG non-IVIG patients, and in 2 of 11 (18%) non-HGG patients (log-rank, 15.31; P=.0005). No severe IVIG-related side effects were recorded.
  
  
  CONCLUSIONS
  Data from this study demonstrate that prophylactic IVIG replacement therapy safely modulates HGG and specific antimicrobial antibodies. Our data also preliminarily suggest that IVIG replacement therapy might decrease the incidence of severe infection in heart recipients with HGG.
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sarmiento
authors.affiliation: Cardiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Diez
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arraya
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Transplant Immunology Group, 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 General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Palomo
authors.affiliation: Cardiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Iago
authors.initials: I
authors.lastname: Sousa
authors.affiliation: Anesthesiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hortal
authors.affiliation: Cardiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Barrio
authors.affiliation: Microbiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Alonso
authors.affiliation: Microbiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Navarro
authors.affiliation: Transfusion Center of the Community of Madrid, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Vicario
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Cruz
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Carbone
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000188:drug therapy*; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors
keywords: clinical trial; heart transplantation; hypogammaglobulinemia; infection; intravenous immunoglobulin