Abstract
Immune responses to lung self-antigens (SAgs), Kα1Tubulin (Kα1T) and Collagen V (ColV), have been implicated as risk factors for chronic rejection following lung transplantation (LTx). The goal is to determine the prevalence of pre-existing antibodies (Abs) to these SAgs in diseases leading to organ failure and investigate their role in primary graft dysfunction (PGD) and chronic rejection.
Pre- and post-Tx sera from 317 LTx patients for diagnoses (COPD: 161, IPF: 50, CF: 55 and Other: 51) between 2000 and 2011 at Washington University (n: 296) and Cleveland Clinic (n: 21) were analyzed for donor specific Abs (DSA) by Flow PRA, Abs to ColV and Kα1T by ELISA and cytokine levels by LUMINEX assay. Subsequent diagnoses of PGD and bronchiolitis obliterans syndrome (BOS) were made in accordance with ISHLT guidelines.
Pre-Tx, 18% with COPD, 44% with IPF (P<0.05), 29% with CF (p<0.05) and 19.6% with other diagnoses (p>0.7) had Abs to Sags. The incidence of PGD was higher in patients with pre-Tx Abs to these Sags compared to those without (80-88% to 42-54%, p<0.05) as was the incidence of BOS at 5 years post-Tx (90% versus 38%). The risk for development of DSA was higher in patients with Abs to Sags (70% versus 28%, p<0.01). In addition, there was elevation in serum pro-inflammatory cytokines, IL-1β (2.5 fold), IL-17 (2.3 fold) and IFN-γ (3.5 fold) and reduction serum IL-10 (1.9 fold) levels (p<0.01) in patients with positive Abs to Sags.
Patients with CF and IPF demonstrated a significantly increased incidence of Abs to lung Sags, Kα1T and ColV. Patients with pre-Tx Abs to Sags were at increased risk for developing PGD, DSA and BOS, therefore strategies to deplete pre-existing Abs to Sags should be considered in order to improve outcomes after LTx.