Screening for Severe Hypogammaglobulinemia in Lung Transplant Recipients

Abstract

<h3>Purpose</h3> Severe hypogammaglobulinemia (HG), IgG <400 mg/dL, is associated with increased infections and mortality post-lung transplant (LT). Pre- and post-LT screening is recommended, but optimal protocols have not been determined and practices vary between LT centers. We designed and implemented a screening program to detect severe HG in LT recipients. <h3>Methods</h3> We developed and implemented standard pre-/post-LT IgG screening protocols through iterative PDSA cycles starting 1/1/19. We collected pre-/post- IgG levels for LT recipients between 1/1/94-10/15/20 to measure process outcomes and inform future improvements. <h3>Results</h3> Both pre- and post-LT IgG screening increased after screening protocols were implemented (Table). Of 45 patients who underwent LT between 1/1/17-10/15/20 and had pre-LT IgG checked, 0% (0) had severe HG, 11% (5) HG (IgG 400-700 mg/dL), 9% (4) isolated low IgG subclasses, 4% (2) isolated low IgA, and 13% (6) isolated low IgM. All 5 patients with pre-LT HG, 2 with associated low IgA and/or IgM, developed severe or clinically significant HG post-LT requiring IgG Replacement Therapy (IgG-RT). Of 249 patients who underwent LT before 6/30/20 and had post-LT IgG checked, severe HG rates were 17% (8/48), 7% (4/60), 5% (3/56), 14% (8/56), 11% (6/53), 6% (3/48), 3% (1/34), and 3% (1/35) at 0.5, 1, 2, 3, 6, 12, 18, and 24 months. Median [range] time from LT to severe HG onset was 90 [14-730] days. Time from severe HG onset to recovery was 31 [16-184] days in 9 patients whose severe HG resolved without IgG-RT. IgG-RT was started in 28 patients 212 [0-3533] days after LT per immunology recommendation. Pre-LT IgG (r=0.78, p=0) and IgG3 (r=0.82, p=0) correlated with the lowest IgG level post-LT. Pre-LT CD27+ (r=-0.58, p=0.007) and CD27+IgM+IgD+ (r=-0.52, p=0.02) B cells inversely correlated with the lowest IgG level post-LT. <h3>Conclusion</h3> Implementation of standard HG screening protocols increased detection of severe HG post-LT and revealed novel findings regarding the significance of immunologic abnormalities in LT recipients.