Intragraft IgG Levels and Donor-Specific anti-HLA Antibodies in Different Phenotypes of Chronic Lung Allograft Dysfunction

Abstract

Purpose Circulating donor specific antibodies (DSA) are a key diagnostic criterion for antibody-mediated rejection (AMR) after lung transplantation (LTx). DSA occur in 10-50% of LTx patients and increase the risk of chronic lung allograft dysfunction (CLAD) and mortality. Detection and interpretation of circulating DSA remains unstandardized and challenging; and discrepancies between serological and pathological/clinical findings are common. Therefore, we aimed to assess presence and relevance of graft DSA (gDSA) in explant lungs with different phenotypes of CLAD. Methods Explant lungs from patients with bronchiolitis obliterans syndrome (BOS, n= 18) and restrictive allograft syndrome (RAS, n=18) were collected at redo-transplantation or autopsy, inflated and fixed in liquid nitrogen fumes. Per lung, two tissue cores were selected from separate regions, assessed for surface density using microCT, and subsequently homogenized. Intragraft IgG antibodies were eluted (Gamma ELU-kit II, Immucor) and total IgG levels were measured via ELISA (Thermo Fisher). Anti-HLA Class I and II antibodies were identified via Luminex (LABScreen LS1A04 and LS2A01, One Lambda). gDSA data was correlated to serum DSA (sDSA) profiles, assessed for all patients included in this study using routine clinical practice. Results Intragraft IgG levels were higher in RAS compared to BOS samples (p Conclusion IgG levels were higher in RAS and in gDSA+ samples. DSA are more prevalent in RAS compared to BOS. gDSA assessment could provide complementary information to sDSA findings. The relevance and applications of gDSA need further investigation.