Hyaluronan and LYVE-1 and allograft function in lung transplantation recipients

Steve Keller,Jewel Imani,Shikshya Shrestha,Hilary J Goldberg,Pierce H Louis,Patrick Burkett,Anthony M Lamattina,Anil J Trindade,Souheil El-Chemaly,Andrew M Courtwright,Miguel Divo,Ivan O Rosas

doi:10.1038/s41598-019-45309-6

Steve Keller, Jewel Imani + Show 10 more

Open Access

https://doi.org/10.1038/s41598-019-45309-6

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Abstract

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients. This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). Chronic lung allograft dysfunction (CLAD)-free survival was also evaluated based on HA and LYVE-1 levels. 78 recipients were enrolled with a total of 115 diagnostic biopsies and 1.5 years of median follow-up. Serum HA was correlated with BAL HA (r = 0.25, p = 0.01) and with serum LYVE-1 (r = 0.32, p = 0.002). There was significant variation in HA and LYVE-1 over time, regardless of ACR status. Levels of serum HA (median 74.7 vs 82.7, p = 0.69), BAL HA (median 149.4 vs 134.5, p = 0.39), and LYVE-1 (mean 190.2 vs 183.8, p = 0.72) were not associated with ACR. CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3–7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2–3.6, p = 0.93). These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients.

Highlights

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients
Elevated levels of HA have been found in recipients who have developed the bronchiolitis obliterans (BOS) subtype of Chronic lung allograft dysfunction (CLAD), there are no data on whether elevated HA levels are associated with risk for developing CLAD25
Per-plate intra-assay coefficient of variation (CV) means were less than 10% for all enzyme-linked immunosorbent assay (ELISA) plates run for HA (3.9 ± 2.0%, n = 9) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) (3.8 ± 0.9%, n = 4) measurement

Summary

Introduction

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3–7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2–3.6, p = 0.93) These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients. We hypothesized that HA and LYVE-1 would be elevated during episodes of ACR and that having an episode of elevated HA would be a risk factor for worse CLAD-free survival

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