Nonspecific immunoglobulin replacement in lung transplantation recipients with hypogammaglobulinemia: a cohort study taking into account propensity score and immortal time bias

Transplantation. 2015 Feb;99(2):444-50. doi: 10.1097/TP.0000000000000339.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Agammaglobulinemia / blood
  • Agammaglobulinemia / diagnosis
  • Agammaglobulinemia / drug therapy*
  • Agammaglobulinemia / immunology
  • Agammaglobulinemia / mortality
  • Biomarkers / blood
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • France
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulins, Intravenous / administration & dosage*
  • Kaplan-Meier Estimate
  • Lung Transplantation / adverse effects*
  • Lung Transplantation / mortality
  • Male
  • Middle Aged
  • Propensity Score
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Immunoglobulin G
  • Immunoglobulins, Intravenous