IgG Replacement Therapy Use in Patients with Hypogammaglobulinemia after Lung Transplant

Secondary hypogammaglobulinemia (HG) occurs in up to 73% of patients in the first year post-lung transplant (LT). Severe HG (sHG) with immunoglobulin (Ig)G levels <400 mg/dL is associated with increased infections and mortality. Although IgG replacement therapy (IGRT) may mitigate adverse outcomes associated with HG, further investigation is needed to understand the optimal role for IGRT in HG management. Data were reviewed for 191 patients who underwent first LT before 11/30/2021 with HG (at least one IgG < 600 mg/dL) post-transplant. Bacterial and fungal microbiology results (bronchoalveolar lavage, induced sputum culture, bronchial lavage), IGRT prescriptions, and IgG levels were chart-reviewed. Antimicrobial prescriptions were extracted from electronic medical records. Active infection (AI) was defined as prescription of a non-prophylactic antimicrobial; severe AI (SAI) as inpatient or intravenous prescription of a non-prophylactic antimicrobial. Positive microbiology results, AI, and SAI were reported in patient-years for the one year after first IgG < 600 mg/dL in 141 patients who never received IGRT (No-IGRT), and for the time between LT and IGRT initiation (Pre-IGRT) as well as the one year after IGRT initiation (Post-IGRT) in 50 patients who received IGRT. IGRT was initiated for secondary HG 82% (41/50), donor specific antibodies 12% (6/50), cytomegalovirus 2% (1/50), and both secondary HG and donor specific antibodies 4% (2/50). Thirty-seven patients started intravenous-IGRT (IVIG), of whom 5 switched to subcutaneous-IGRT (SCIG) during the course of treatment. Thirteen started SCIG, of whom 2 switched to IVIG. IVIG was administered for 18 ± 18 (mean ± standard deviation) doses of 41 ± 22 grams/month over 71 ± 74 weeks. SCIG was administered for 74 ± 53 doses of 27 ± 20 grams/month over 86 ± 64 weeks. There were more AI and SAI per patient-year Pre-IGRT (15.8 and 11.7, respectively) than No-IGRT (4.9 and 2.6) and Post-IGRT (8.3 and 5.8). Positive microbiology results per patient-year were 3.8 Pre-IGRT, 3.3 Post-IGRT, and 2.3 No-IGRT. Among 29 patients with sHG, positive microbiology results per patient-year were 4.8 Pre-IGRT, 4.3 Post-IGRT, and 3.1 No-IGRT.Table 1. Infectious Agents Detected on Pulmonary MicrobiologyOrganism (n, %)No-IGRT (n = 318)Pre-IGRT (n = 251)Post-IGRT (n = 166)Penicillium spp.52 (16)36 (14)13 (8)Aspergillus spp.59 (18)34 (13)28 (17)Staphylococcus epidermidis8 (3)21 (9)7 (4)Pseudomonas aeruginosa20 (7)17 (7)18 (11)Staphylococcus aureus2 (1)15 (6)12 (7)Enterococcus spp.0 (0)10 (4)3 (2)Mycobacterium spp.7 (2)12 (5)4 (2)Sterile mycelium8 (3)9 (3)3 (2)Stenotrophomonas maltophilia3 (1)9 (3)8 (5)Enterobacter cloacae complex1 (<1)8 (3)3 (2)Escherichia coli4 (1)7 (3)7 (4)Haemophilus parainfluenzae44 (13)4 (2)9 (5)Klebsiella pneumoniae11 (3)2 (1)8 (5)Other99 (31)67 (27)43(26)Legend: The 735 specific microorganisms detected on bronchoalveolar lavage, sputum culture and bronchial lavage are shown. Abbreviation: Species (spp.) Table 1. Infectious Agents Detected on Pulmonary Microbiology Legend: The 735 specific microorganisms detected on bronchoalveolar lavage, sputum culture and bronchial lavage are shown. Abbreviation: Species (spp.) These findings suggest that IGRT was utilized for patients who presented with infections in addition to HG, with a possible decrease in antimicrobial use after initiation.