Abstract
Current evidence demonstrates an important role for cross talk between alloimmunity and autoimmunity in the pathogenesis of chronic rejection following human lung transplantation (LTx) manifested as bronchiolitis obliterans syndrome (BOS). We recently demonstrated that preemptive antibody directed therapy (IVIG and Rituximab) in patients who develop de novo anti-HLA antibodies (DSA) resulted in removal of DSA and greater freedom from BOS. The goal of this study is to determine the impact of antibody directed therapy on autoimmunity and its influence in reducing the incidence of BOS.
Adult lung transplant recipients (n=116) were analyzed. BOS was diagnosed by ISHLT guidelines. DSA were measured by LABScreen Single antigen beads by Luminex every 3 months, antibodies (Abs) to self-antigens K-α1-tubulin (Kα1T) and Collagen V (Col-V) by ELISA and cytokines by Luminex kit.
Among 116 LTx, 65 developed DSA within 3 months of LTx and were treated with IVIG and/or rituximab. Among the DSA cleared BOS- patients (n=28), there was a significant drop in Abs to Col-V (from 23/28 to 12/28) and Kα1T (from 25/28 to 14/28, p <0.01). However, among DSA cleared BOS+ patients (n=10) there was minimal decline of auto-Abs (anti-Col-V: from 10/10 to 7/10, and anti- Kα1T: from 10/10 to 8/10 p= 0.21). Among those with persistent DSA (n=23) and BOS+ (n=14) the drop in auto-Abs following therapy was insignificant. Cytokine analysis on the therapy group demonstrated that among patients who cleared DSA and who were free from BOS had decreased levels of pro-inflammatory cytokines (namely IL-1β (3.2 fold decrease), IL-17 (3.0), IFN-γ (2.3)) and a concomitant increase in anti-inflammatory cytokine IL-10 (3.7 fold increase, p<0.01 for all) within 6 months of administration of therapy.
Our results demonstrate that antibody directed therapy results in decreased circulating levels of pro inflammatory cytokines and development of auto-Abs and increased freedom from BOS.