Efficacy of extracorporeal photopheresis in clearance of antibodies to donor-specific and lung-specific antigens in lung transplant recipients

Gautam Baskaran, Venkataswarup Tiriveedhi, Sabarinathan Ramachandran, Aviva Aloush, Brenda Grossman, Ramsey Hachem, Thalachallour Mohanakumar, Gautam Baskaran, Venkataswarup Tiriveedhi, Sabarinathan Ramachandran, Aviva Aloush, Brenda Grossman, Ramsey Hachem, Thalachallour Mohanakumar

Abstract

Background: Extracorporeal photopheresis (ECP) has been used to treat chronic rejection after lung transplantation (LTx). We investigated the effect of ECP on several immune parameters that have been associated with poor lung function, including donor-specific antibodies (DSA) to human leukocyte antigen (HLA), antibodies against the lung-associated self-antigens (SAg), Kα1-tubulin (Kα1T), collagen I and V, and circulating levels of pro-inflammatory and anti-inflammatory cytokines.

Methods: Sera were collected from post-LTx patients diagnosed with bronchiolitis obliterans before and 6 months after initiation of ECP. DSA and cytokine levels were measured by Luminex (Invitrogen, Carlsbad, CA). Changes in lung function over the 6 months preceding and after the initiation of ECP were measured by retrospective analysis of spirometry performed at routine clinic visits.

Results: ECP was associated with a significant decline in DSA levels as well as antibodies to lung-associated SAg. ECP also reduced circulating levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. These immunologic changes were associated with a significant 63% reduction in the rate of decline in forced expiratory volume in 1 second over a 1-year period. Though statistically insignificant, a higher rate of clearance of antibodies to lung-associated SAg was strongly associated with better response to ECP.

Conclusions: ECP is associated with a reduction in the levels of circulating DSA, antibodies to lung-associated SAg (Kα1T, collagen I, and collagen V), and circulating levels of several pro-inflammatory cytokines. We propose that these changes contribute to the beneficial effect of ECP in reducing the decline in lung function.

Keywords: chronic rejection; cytokines; donor-specific antibodies; extracorporeal photopheresis; lung transplantation.

Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Percentage change in DSA levels in patients who underwent ECP. Change in DSA levels, expressed as percentage increase or decrease from pre-ECP treatment values, in patients (1–23) who underwent ECP.
Figure 2. Changes in autoimmune antibody (SAg)…
Figure 2. Changes in autoimmune antibody (SAg) levels with ECP
Levels of antibodies to Col 1, Col 5 and K Kα1T pre and post photopharesis (pp). Symbols represent means and error bars represent the 95% confidence interval.
Figure 3. Mean cytokine levels pre and…
Figure 3. Mean cytokine levels pre and post initiation of ECP
Cytokine levels pre and post photopharesis (pp). Symbols represent means and error bars represent the 95% confidence interval.

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