title: Nonspecific immunoglobulin replacement in lung transplantation recipients with hypogammaglobulinemia: a cohort study taking into account propensity score and immortal time bias.
abstract: BACKGROUND
  After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival.
  
  
  METHODS
  We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed.
  
  
  RESULTS
  Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups.
  
  
  CONCLUSIONS
  Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.
authors.affiliation: 1 Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux, CHU Grenoble, Grenoble, France. 2 INSERM CIC3, Centre d'Investigation Clinique, CHU Grenoble, Grenoble, France. 3 Université Grenoble Alpes, UFR de Pharmacie, Grenoble, France. 4 Pharmacie hospitalière, CHU Grenoble, Grenoble, France. 5 CNRS, TIMC-IMAG 5525, Grenoble, France. 6 Clinique Universitaire des Maladies infectieuses, CHU Grenoble, Grenoble, France. 7 Laboratoire d'histocompatibilité, Etablissement Français du sang Rhône-Alpes, Lyon, France. 8 Univ. Grenoble Alpes, LBFA, Grenoble, France. 9 INSERM, LBFA, F-38000 Grenoble, France. 10 CRNH Rhône-Alpes, Pierre-Bénite, France. 11 European Institute of Systems Biology and Medicine, Lyon, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Claustre
authors.forename: Sébastien
authors.initials: S
authors.lastname: Quétant
authors.forename: Boubou
authors.initials: B
authors.lastname: Camara
authors.forename: Marion
authors.initials: M
authors.lastname: France
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schummer
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bedouch
authors.forename: Patricia
authors.initials: P
authors.lastname: Pavese
authors.forename: Christel
authors.initials: C
authors.lastname: Saint Raymond
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bardy
authors.forename: Dominique
authors.initials: D
authors.lastname: Masson
authors.forename: Hubert
authors.initials: H
authors.lastname: Roth
authors.forename: Christophe
authors.initials: C
authors.lastname: Pison
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous