Original Pre-Clinical Science
Pre-transplant antibodies to Kα1 tubulin and collagen-V in lung transplantation: Clinical correlations

https://doi.org/10.1016/j.healun.2013.06.003Get rights and content

Background

Immune responses to lung-associated self-antigens (SAgs) have been implicated in chronic lung allograft rejection. The goals of this study were to determine the prevalence of pre-existing antibodies (Abs) to the SAgs in pulmonary diseases and the association between pre-existing Abs to SAgs and the development of primary graft dysfunction (PGD), donor-specific antibodies (DSA), and chronic rejection.

Methods

Pre- and post-transplant sera were analyzed from 317 lung transplant (LTx) recipients between 2000 and 2011 with diagnosis of chronic obstructive disease (n = 161), idiopathic pulmonary fibrosis (IPF; n = 50), cystic fibrosis (CF; n = 55), and others (n = 51). Samples were analyzed for Abs to SAgs by enzyme-linked immunosorbent assay, and DSA and cytokines by Luminex. The clinical diagnosis of PGD and bronchiolitis obliterans syndrome (BOS) was based on International Society for Heart and Lung Transplantation guidelines.

Results

The overall prevalence of Abs to SAgs was 22.71%, including 18% in chronic obstructive pulmonary disease (p = 0.033), 34% in IPF (p = 0.0006), 29% in CF (p = 0.0023), and 19.6% in other diagnoses (p = 0.044). The incidence of PGD (88% vs 54%, p < 0.05), DSA (70% vs 45%, p < 0.01), and BOS (90% vs 38% (p < 0.001) after LTx was significantly higher in patients with pre-LTx Abs to SAgs than without. Pro-inflammatory cytokines (interleukin-1β, interleukin-17, and interferon-γ) were elevated in patients who had pre-LTx Abs to SAgs, along with a reduction in anti-inflammatory interleukin-10.

Conclusions

Patients with IPF and CF have the highest prevalence of Abs to SAgs. Patients with pre-existing Abs to SAgs are at increased risk for development of PGD, DSA, and BOS. Strategies to remove pre-existing Abs to SAgs should be considered to improve lung allograft outcome.

Section snippets

Methods

The Washington University Human Studies Committee approved this study. All patients were included in the study after informed consent.

Increased prevalence of Abs to SAgs Kα1T, Col-I, and Col-V in IPF, CF, and COPD patients listed for LTx

Previous studies have demonstrated a significant correlation between the development of Abs to SAgs and development of DSAs and BOS after human LTx.16 To determine the incidence of pre-existing Abs to SAgs in patients listed for LTx, we analyzed sera from 317 patients listed for LTx at Washington University and Cleveland Clinic between 2000 and 2011. As reported in Table 1, 29 of 161 COPD (18.01%; p = 0.033), 17 of 50 IPF (34%; p = 0.0006), 16 of 55 CF (29.1%; p = 0.0023), and 10 of 51 patients

Discussion

Studies from our laboratory, and others, have demonstrated that humoral and cellular immunity to the lung-associated SAgs, Kα1T and Col-V, can pre-dispose patients to develop BOS.9, 11, 19, 20 In a previous report from our center of 142 patients, we demonstrated that patients with pre-existing Abs to lung-associated SAgs have an increased risk of developing PGD, DSAs, and BOS.16 However, because of our limited sample size, we were unable to comment on the incidence of PGD, DSA formation, and

Disclosure statement

The authors thank Billie Glasscock for her help in preparing this manuscript.

This work was supported by National Institutes of Health grant HL-056643 and the BJC Foundation (T.M.).

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

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