Correlative Changes in Macrophage Polarization and Pulmonary Microbiota in Lung Transplant Recipients

Correlative Changes in Macrophage Polarization and Pulmonary Microbiota in Lung Transplant Recipients

Abstracts S51 Purpose: Heart transplantation (HTx) is an available therapeutic option in the Middle East. The first adult Htx was performed at our hos...

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Abstracts S51 Purpose: Heart transplantation (HTx) is an available therapeutic option in the Middle East. The first adult Htx was performed at our hospital 1989. The purpose of this study was to report demographics characteristic of our recipients and donors, and show our survival data. Methods: Retrospective analysis of prospectively collected data from all heart transplanted since 1989 through October 2014. Results: During this period of more than 25 years, 204 patients underwent 205 HTx. Mean recipient age was 33±13 (range 11-59) and 75% (n= 154) were male. Six transplanted patients (3%) were from other countries (UAE-2, Bahrain-2, Yemen-1 and Sudan-1). Seven donors were from Kuwait (4 donors during 3 months -July to October 2014). Only 2-donors (0.98%) were Saudi and all the other were expatriates. Main indications for HTx were: cardiomyopathy (63%), Coronary artery disease 26%, valvular heart disease 8% congenital heart disease (2%) and retransplantation (0.7%). Mean follow up was 4.3±4.4 years (median 3.1, interquartile range 0.8-6.5, and interval 0-22) and no patients were lost to follow up. Survival for transplanted patients was 89%, 82%, 73%, 70% and 56% at 30 days, 1, 3, 5 and 10 years follow up. The survival data were significantly higher in the new transplantation era (since 2006), with tailored immunosuppressive therapy, higher volume (12-19 HTx per year) and increased experience (Figure) despite significantly older recipients and donors (36±13 vs. 27±13 years, p< 0.001 and 32±10 vs.21±18 years, p= 0.008, respectively) Conclusion: With this current number of HTx, KFSH&RC belongs to the group of 38 high-volume international centers. With better organization, and a close collaboration at different levels between Gulf countries, KFSH&RC with available competence can be the HTx referral centre for all Gulf countries patients. 

1( 14) Primary Immunosuppression and Outcome Differences After Heart Transplantation: Cyclosporin/Azathioprine/Steroid vs. Tacrolimus/ Mycophenolate mofetil/Steroid - 22 Years’ National Experience of Korea H. Lee ,1 J. Kim,2 G. Lee,3 E. Jeon.3  1Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of; 2Internal Medicine, Asan Medical Center, Seoul, Korea, Republic of; 3Internal Medicine, Samsung Medical Center, Seoul, Korea, Republic of. Purpose: The superiority of newer immunosuppressant regimen consisting of tacrolimus + mycophenolate mofetil + steroid (TMS) over older regimen of cyclosporin + azathioprine + steroid (CAS) is often suggested. However, long term study results are rarely published. The aim of this study was to evaluate long-term outcomes of patients undergoing heart transplantation based on primary immunosuppression regime. Methods: We analyzed national registry of all HT patients between 1992 and 2012, comparing outcomes based on primary immunosuppressions (CAS versus TMS). Patients who died before starting immunosuppression were excluded. Results: Among 776 heart transplantation patients, 91 patients were treated with CAS and 263 patients were treated with TMS. 1) Patients treated with CAS mainly received heart transplantation before 2000, whereas patients treated with PMS mainly received heart transplantation after 2006. The donor

and recipient age were both significantly lower in CAS group compared with PMS group. 2) Kaplan-Meier analysis showed rejection-free survival was significantly longer in PMS group compared with CAS group. However, interestingly, overall patients survival rate is not significantly between two groups. 3) Multivariate analysis showed that initial immunosuppressant regimen did not result in significant difference in survival. Conclusion: Although newer regimen consisting of PMS near completely replaced older regimen with CAS, there were no differences in long term survival between two groups. 1( 15) Correlative Changes in Macrophage Polarization and Pulmonary Microbiota in Lung Transplant Recipients E. Bernasconi ,1 A. Koutsokera,1 C. Pattaroni,1 D. Dumas,1 B. Camara,2 B.J. Marsland,1 C. Benden,3 C. Pison,2 J. Aubert,4 L.P. Nicod.5  1Pulmonary Division, CHUV, Lausanne, Switzerland; 2CHU, Grenoble, France; 3University Hospital Zurich, Zurich, Switzerland; 4Pulmonary Division, CHUV and STCS, Lausanne, Switzerland; 5Pulmonary Division, CHUV and SysCLAD FP7 Consortium, Lausanne, Switzerland. Purpose: The lung microbiota has distinct constituents depending on local inflammatory status. As yet, the direct implications of the lung microbiota in disease development is unknown. We hypothesized that the lung microbiota directly influences macrophage functionality and consequently long-term graft survival. Methods: DNA and total RNA were isolated from 184 bronchoalveolar lavages obtained from 110 patients between 0.5 and 24 months post-lung transplantation (LTX). Expression of a set of genes involved in prototypic macrophage functions was quantified using RT-qPCR. Microbiota composition at phylum level was determined using 16S rDNA amplification. Results: A majority of samples obtained at 3 months post-LTX displayed macrophage polarization, either with inflammation (M1, 23%) or remodeling (M2, 40%) predominance. At later time-points, the percentage of samples with M2 polarization increased at the expense of M1 samples (57% vs. 9% at 12 months). In comparison to non-polarized and M2 samples, M1 samples displayed a 2.9 and 11.6-fold increase in TNF and COX-2 expression, respectively, as well as higher neutrophil counts (42% vs. 4%) reflecting inflammation. In contrast, M2 samples were characterized by a 3.2-fold increase in PDGFD expression and a 2.6-fold higher TIMP1 to MMP12 expression ratio indicating tissue remodeling. The composition of lung microbiota was found to vary in parallel with macrophage polarization and to be dominated by different groups of bacteria depending on the type of macrophage activation. Conclusion: Alveolar macrophage polarization in conjunction with microbiota composition reflects dynamic changes in lung transplant recipients. Long-term longitudinal follow-up of patients with persistent macrophage polarization and altered microbiota will elucidate whether these conditions may predict a negative outcome for graft survival. 1( 16) Cardiac Allograft Tolerance Induction via Anti-LFA-1 Monotherapy Is Dependent on an Indirect CD8 T-Cell R.J. Plenter ,1 M.K. Nelsen,2 M.R. Zamora,1 R.G. Gill,2 B.A. Pietra.3  1Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, CO; 2Colorado Center for Transplantation Care, Research and Education, University of Colorado Denver, Aurora, CO; 3Division of Pediatric Cardiology, University of Florida, Gainesville, FL. Purpose: Requirements for tolerance induction appear to be agent specific. Having previously demonstrated that NK and NKT cells are not required, in this study, we sought to investigate some further requirements for tolerance induction to cardiac allografts utilizing anti-LFA-1 mAb monotherapy. Methods: BALB/c or C3H hearts were transplanted into B6, B6rag-/- or beta2M mice and were untreated or treated with anti-LFA-1 or control rat IgG or anti-CD8 (at time of transplant or at POD 28) or anti-CD40L or adoptively transferred with tolerized or naive splenocytes. Dominant tolerance (BALB/c-B6rag-/- + tolerant and naïve splenocytes) and linked suppression (BALB/c/C3H F1-B6rag-/- + tolerant splenocytes) experiments were also performed. To investigate a possible role for the direct pathway of antigen