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

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.