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Introduction: Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR). Methods: Serum anti-Human Leukocyte Antigen (HLA) antibodies were determined using class I and class II antibody-coated latex beads (FlowPRATM Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch. Results: We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%; P = 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed de novo anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA. Conclusion: Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR. [ABSTRACT FROM AUTHOR]

In antibody-mediated rejection (ABMR), the graft endothelium is at the forefront of the kidney transplant against the assault from the recipient's humoral immune system, and is a target of the latter. The present study investigated the effect of antibodies against human leukocyte antigen (HLA) class I (anti-HLAI) on the immunological properties of human glomerular endothelial cells. Additionally, the effect of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) inhibitor (everolimus), or the general control nonderepressible 2 kinase (GCN2K) activator (halofuginone) on anti-HLAI antibody-mediated alterations was assessed. Cell integrity was examined, an lactate dehydrogenase (LDH) release assay was performed and cleaved caspase-3 levels were determined. Furthermore, cell proliferation was analyzed by performing a bromodeoxyuridine assay and the cellular proteins involved in signal transduction or immune effector mechanisms were assessed via western blotting. IL-8, monocyte chemoattractive protein-1 (MCP-1), von Willebrand factor (vWF) and transforming growth factor-beta 1 (TGF-β1) were assayed via ELISA. The results revealed that anti-HLAI triggered integrin signaling, activated mTOR and GCN2K, preserved cell integrity and promoted cell proliferation. Additionally, by increasing intercellular adhesion molecule 1 (ICAM-1), HLA-DR, IL-8 and MCP-1 levels, anti-HLAI enhanced the ability of immune cells to interact with endothelial cells thus facilitating graft rejection. Contrarily, by upregulating CD46 and CD59, anti-HLAI rendered the endothelium less vulnerable to complement-mediated injury. Finally, by enhancing vWF and TGF-β1, anti-HLAI may render the endothelium prothrombotic and facilitate fibrosis and graft failure, respectively. According to our results, mTORC1 inhibition and GCN2K activation may prove useful pharmaceutical targets, as they prevent cell proliferation and downregulate ICAM-1, IL-8, MCP-1 and TGF-β1. mTORC1 inhibition also decreases vWF. [ABSTRACT FROM AUTHOR]