Clinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of present study was to evaluate whether a specific set of miRNAs were significantly regulated by ECP. Total RNA was isolated from serum of patients with established BOS grade 1–2 prior to the start and after 6 months of ECP treatment. We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found. SMAD4 mRNA was found to be a common target of these two miRNAs in prediction pathways analysis, and a significant downregulation was found at 6 months in PBMCs of a subgroup of ECP-treated patients. According to previous evidence, the upregulation of miR-155 might be correlated with a pro-tolerogenic modulation of the immune system. Our analysis also suggests that SMAD4 might be a possible target for miR-155-5p. Further longitudinal studies are needed to address the possible role of miR-155 and its downstream targets.

Summary Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low‐dose maintenance immunosuppression in a large single‐center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low‐dose maintenance immunosuppression were included in the analysis. Short‐ and long‐term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher‐grade ACR at 1, 5, and 10 years was 98%, 96%, and 96%, respectively. Thirty‐nine patients (5%) developed clinical AMR. Twenty‐one percent of patients developed high‐grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3 months. Sixty‐two patients (9%) developed a malignancy during follow‐up. Freedom from CLAD at 1, 5, and 10 years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low‐dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long‐term survival.

Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p < 0.001) and miR-486 (p < 0.001). Expression of 3 miRNAs changed within the alemtuzumab group: miR-146 (p < 0.001), miR-155 (p < 0.001) and miR-31 (p < 0.001). Levels of IL-13, IL-4, IFN-γ, BAFF, IL-5, IL-9, IL-17F, IL-17A and IL-22 were different one year after transplantation compared to baseline. In no-induction group, concentration of sCD27, sB7.2 and sPD-L1 increased overtime. Expression of miR-23b, miR-146, miR-486, miR-155 and miR-31 was different in LTx recipients who received alemtuzumab compared to recipients without induction therapy. The observed cytokine pattern suggested proliferation of specific B cell subsets in alemtuzumab group and co-stimulation of T-cells in no-induction group.

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