Antibodies to K-α 1 tubulin and collagen V are associated with chronic rejection after lung transplantation

R R Hachem, V Tiriveedhi, G A Patterson, A Aloush, E P Trulock, T Mohanakumar, R R Hachem, V Tiriveedhi, G A Patterson, A Aloush, E P Trulock, T Mohanakumar

Abstract

Bronchiolitis obliterans syndrome (BOS), the clinical correlate of chronic rejection after lung transplantation, is the leading obstacle to better long-term outcomes. We previously instituted a clinical protocol to screen for donor-specific human leukocyte antigen (HLA) antibodies (DSA) and a preemptive antibody-directed therapy protocol consisting of rituximab and/or intravenous immune globulin. In this study, we retrospectively analyzed serum samples from lung transplant recipients (n = 108) for antibodies to self-antigens (K-α 1 tubulin and collagen V) before and after antibody-directed therapy and correlated the results with the subsequent development of BOS. Seventy-two of the 108 recipients developed antibodies to self-antigens. There was a correlation between the development of antibodies to self-antigens and DSA. Sixteen of the 54 patients who had antibodies to self-antigens and were treated with antibody-directed therapy cleared the antibodies, and they were significantly less likely to develop BOS than those who had persistent antibodies. Furthermore, those who cleared DSA after treatment but had persistent antibodies to self-antigens were significantly more likely to develop BOS than those who cleared these antibodies. We conclude that antibodies to self-antigens are an important risk factor for the development of BOS.

© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

Figure 1
Figure 1
Flow chart of patients through the study including screening, treatments, and outcomes. DSA: donor-specific HLA antibodies. Antibodies to self-Ags: antibodies to self-antigens. IVIG: intravenous immune globulin.
Figure 2
Figure 2
Freedom from antibodies to self-antigens for the entire cohort.
Figure 3
Figure 3
A. Among patients who cleared DSA but had persistent antibodies to self-antigens and developed BOS (n = 13), there was no significant change in pro-inflammatory cytokine (IL-1β, IFN-γ, and IL-17) concentrations or in IL-10 concentrations before and after antibody-directed therapy. B. Among patients who cleared DSA and antibodies to self-antigens and did not develop BOS (n = 10), there was a significant reduction in pro-inflammatory cytokine concentrations and a significant increase in IL-10 after antibody-directed therapy. C. Among patients with persistent DSA and persistent antibodies to self-antigens who developed BOS (n = 14), there was no significant change in pro-inflammatory cytokine (IL-1β, IFN-γ, and IL-17) concentrations or in IL-10 concentrations before and after antibody-directed therapy. D. Among patients with persistent DSA who cleared antibodies to self-antigens and did not develop BOS ( n = 3), there was a significant reduction in pro-inflammatory cytokine concentrations and a significant increase in IL-10 after antibody-directed therapy.
Figure 4
Figure 4
Among patients who had antibodies to self-antigens but did not have DSA, those who developed BOS (n = 12) had significantly higher pro-inflammatory cytokine (IL-1β, IFN-γ, and IL-17) concentrations and lower IL-10 concentrations than those who did not develop BOS (n = 5).

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