Mathematical modeling of peripheral blood neutrophil kinetics to predict CLAD after lung transplantation.
Abstract BACKGROUND: The presence of neutrophils in the lung was identified as a factor associated with CLAD but requires invasive samples. The aim of this study was to assess the kinetics of peripheral blood neutrophils after lung transplantation as early predictor of CLAD. METHODS: We retrospectively included all recipients transplanted in our center between 2009 and 2014. Kinetics of blood neutrophils were evaluated to predict early CLAD by mathematical modeling using unadjusted and adjusted analyses. RESULTS: 103 patients were included, 80 in the stable group and 23 in the CLAD group. Bacterial infec...
Source: Transplant Immunology - July 22, 2020 Category: Transplant Surgery Authors: Coiffard B, Reynaud-Gaubert M, Rey JB, Cousin E, Grosdidier C, Nicolino-Brunet C, Dignat-George F, Papazian L, Thomas PA, Barbolosi D, Serre R Tags: Transpl Immunol Source Type: research

Toll-like 4 receptor (TLR4) expression on peripheral blood mononuclear cells in renal transplant recipients with pre-transplant chronic interstitial nephritis indicates patients at risk of graft deterioration.
CONCLUSION: In CIN, both TLR4ex and Tac appear to be a useful positive predictor of the effectiveness of immunosuppression. Chronic pyelonephritis indirectly promotes faster progression of chronic transplanted kidney disease. PMID: 32693120 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - July 18, 2020 Category: Transplant Surgery Authors: Zmonarski SC, Miroslaw B, Tomasz G, Katarzyna M, Oktawia M, Marta M, Joanna Z, Krzysztof L, Tomasz D, Magdalena K Tags: Transpl Immunol Source Type: research

MiR-669b-3p regulates CD4+ T cell function by down-regulating indoleamine-2, 3-dioxygenase.
CONCLUSION: Our results advance the current understanding of the immune regulatory function of miRNA and shed light on the role of miR-669b-3p in CD4+ T cells, suggesting that miR-669b-3p is a potential target for acute allograft rejection. PMID: 32687860 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - July 17, 2020 Category: Transplant Surgery Authors: Li C, Wang X, Yuan F, Zhao Z, Zhang B, Zhang J, Li W, Liu T Tags: Transpl Immunol Source Type: research

Improving HLA matching in living donor kidney transplantation using kidney paired exchange program.
CONCLUSIONS: This strategy is a viable alternative for compatible pairs seeking a better matched kidney and Portuguese KEP program should allow them this possibility. PMID: 32634478 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - July 4, 2020 Category: Transplant Surgery Authors: Tafulo S, Malheiro J, Dias L, Lobato L, Ramalhete L, Martinho A, Bolotinha C, Costa R, Ivo M Tags: Transpl Immunol Source Type: research

Impact of HLA polymorphisms among cadaveric donors on kidney graft allocation.
This study provides data on HLA-A, -B, and -DRB1 frequencies among 874 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadaveric donors (422 from Croatia and 285 from Eurotransplant). Patients positive for HLA-B*07, -B*08, or -B*44 genes more often received a kidney from ET donors, while HLA-DRB1*11 and -DRB1*16 positive patients more frequently received a kidney from CRO donors. ABDR MM 000 was more frequently present in the case ...
Source: Transplant Immunology - July 2, 2020 Category: Transplant Surgery Authors: Grubic Z, Kamenaric MB, Kljajic J, Jankovic KS, Maskalan M, Zunec R Tags: Transpl Immunol Source Type: research

Investigating complement mediated interference in class I HLA-specific antibodies following renal transplantation.
DISCUSSION: Our data indicates that both EDTA and BSC are suitable assays in overcoming CMI. We recommend that all clinical laboratories adopt a validated assay designed specifically to abrogate CMI for all potential renal transplant recipients, as the standard assay is inhibited in nearly 20% of a post-transplant cohort. PMID: 32574596 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - June 20, 2020 Category: Transplant Surgery Authors: Goldsmith P, Lowe D, Wong C, Howse M, Ridgway D, Hammad A, Mehra S, Christmas S, Gebel H, Bray R, Jones A Tags: Transpl Immunol Source Type: research

Guy Alexandre - An appreciation of his innovative contributions to organ transplantation.
Abstract Guy Alexandre made major contributions to organ transplantation that, in my opinion, have not been sufficiently recognized by the transplant community. To make his contributions better known, I present a brief summary of the innovations for which he was largely responsible. As a research fellow at the Peter Bent Brigham Hospital in Boston in 1962-3, under subsequent Nobelist Joseph Murray, he contributed to the establishment of pharmacologic immunosuppressive therapy (initiated by Roy Calne) in patients undergoing renal allotransplantation. After his return to his native Belgium, he carried out the first ...
Source: Transplant Immunology - June 15, 2020 Category: Transplant Surgery Authors: Cooper DKC Tags: Transpl Immunol Source Type: research

Diagnosis and treatment of acute graft-versus-host disease after liver transplantation: A report of 11cases.
CONCLUSIONS: The diagnostic criteria of aGVHD is mainly based on time, clinical symptoms and the percentage of donor T lymphocytes in peripheral blood. The concept of "aGVHD induced by immunosuppression" provides important guidance in the immunosuppressant management, control, or prevention of infection. Support treatment is very important in the treatment of aGVHD. PMID: 32540505 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - June 12, 2020 Category: Transplant Surgery Authors: Zhao XF, Lin DD, Li N, Ju-Shan, Guo QL, Wang L Tags: Transpl Immunol Source Type: research

Limited efficacy of rapamycin monotherapy in vascularized composite allotransplantation.
Abstract BACKGROUND: Vascularized composite allotransplantation (VCA) is a novel and life-enhancing procedure to restore a patient's function and/or appearance. Current immunosuppression in VCA recipients is based on calcineurin inhibitor (CNI) therapy that can lead to severe complications, such that inducing immune tolerance is a major goal of VCA research. In contrast to CNI, rapamycin (RPM) is thought to be beneficial to the development of immune tolerance by suppressing T-effector cells (Teffs) and expanding T-regulatory (Treg) cells. However, we found high dose RPM monotherapy prolonged VCA survival by only a...
Source: Transplant Immunology - June 11, 2020 Category: Transplant Surgery Authors: Xu H, Steinberger Z, Wang L, Han R, Zhang Y, Hancock WW, Levin LS Tags: Transpl Immunol Source Type: research

Predictive value of HLAMatchmaker and PIRCHE-II scores for de novo donor-specific antibody formation after adult and pediatric liver transplantation.
ros M Abstract Production of de novo DSA (dnDSA) is associated with an increased risk of antibody mediated rejection after liver transplantation. Antibodies not only recognize the entire antigen but are able to bind specific functional epitopes present on the HLA molecule surface. The HLAMatchmaker and the PIRCHE-II (predicted indirectly recognizable HLA epitopes) algorithms are able to determine predictive epitope mismatches scores and de novo DSA (dnDSA) synthesis based on alloreactive eplets' identification. The aim of the present study was to assess, for the first time in liver transplantation, the complementa...
Source: Transplant Immunology - May 15, 2020 Category: Transplant Surgery Authors: Hamada S, Dumortier J, Thévenin C, Pageaux GP, Faure S, Guillaud O, Boillot O, Lachaux A, Luscalov DA, Dubois V, Meszaros M Tags: Transpl Immunol Source Type: research

The NLRP3 inhibitor Mcc950 attenuates acute allograft damage in rat kidney transplants.
PMID: 32407873 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - May 11, 2020 Category: Transplant Surgery Authors: Zou XF, Gu JH, Duan JH, Hu ZD, Cui ZL Tags: Transpl Immunol Source Type: research

Outcome of donor lymphocyte infusion for fall in chimerism after hematopoietic stem cell transplant.
Abstract Achievement of complete donor chimerism after an allogeneic hematopoietic stem cell transplant is necessary for elimination of underlying malignant disease. A decline in donor chimerism may herald an impending relapse and therefore, early recognition and intervention plays an important role in such cases. A 32 year old male patient diagnosed as a case of Philadelphia positive mixed phenotypic acute leukaemia underwent a peripheral blood hematopoietic stem cell transplant (HSCT) with his sibling as donor. During follow-up, a fall in donor chimerism was observed from 91.86% on day +37 to 88.83% on day +57...
Source: Transplant Immunology - May 6, 2020 Category: Transplant Surgery Authors: Pandey P, Setya D, Kaul E, Ranjan S, Kumar P Tags: Transpl Immunol Source Type: research

Flow cytometry crossmatching to investigate kidney-biopsy-proven, antibody-mediated rejection in patients who develop de novo donor-specific antibodies.
CONCLUSION: An FC-XM assay was unable to discriminate between cases with or without ABMR on biopsy findings; it had a low positive predictive value (
Source: Transplant Immunology - May 5, 2020 Category: Transplant Surgery Authors: Usureau C, Jacob V, Clichet V, Presne C, Desoutter J, Poulain C, Choukroun G, Guillaume N Tags: Transpl Immunol Source Type: research

Immediate impact of COVID-19 on transplant activity in the Netherlands.
This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs. PMID: 32371150 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - May 1, 2020 Category: Transplant Surgery Authors: de Vries APJ, Alwayn IPJ, Hoek RAS, van den Berg AP, Ultee FCW, Vogelaar SM, Haase-Kromwijk BJJM, Heemskerk MBA, Hemke AC, Nijboer WN, Schaefer BS, Kuiper MA, de Jonge J, van der Kaaij NP, Reinders MEJ Tags: Transpl Immunol Source Type: research

Differential effects of Belatacept on virus-specific memory versus de novo allo-specific T cell responses of kidney transplant recipients and healthy donors.
Falk CS Abstract Belatacept, Nulojix®, inhibits the interaction of CD28 on naïve T cells with B7.1/B7.2 (CD80/86) on antigen presenting cells, leading to T cell hyporesponsiveness and anergy and is approved as immunosuppressive drug in kidney transplantation. Due to its specificity for B7.1/2 molecules, side effects are reduced compared to other immunosuppressive drugs like calcineurin- and mTOR-inhibitors. Kidney transplant recipients under Belatacept-based immunosuppression presented with superior renal function and similar graft survival seven years after transplantation compared to cyclosporine treatm...
Source: Transplant Immunology - April 21, 2020 Category: Transplant Surgery Authors: Kühne JF, Neudörfl C, Beushausen K, Keil J, Malysheva S, Wandrer F, Haller H, Messerle M, Blume C, Neuenhahn M, Schlott F, Hammerschmidt W, Zeidler R, Falk CS Tags: Transpl Immunol Source Type: research

The implication of genetic variation in the complement C3 allotypes on the first-year allograft outcome after live donor liver transplantation.
CONCLUSION: In the liver allograft recipients, C3-SF and C3FF genotypes significantly associated with acute rejection with the C3F allele more prevalent than the C3S. C3SS genotype increases survival without significant association. PMID: 32305505 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - April 16, 2020 Category: Transplant Surgery Authors: Awad SM, Taha M, Omar M, Khalil A Tags: Transpl Immunol Source Type: research

Gastric submucosal alleviated pro-inflammation cytokines mediated initial dysfunction of islets allografts.
Abstract BACKGROUND: The liver and renal capsule are the most common site for experimental pancreatic islet transplantation, but it is not optimal. Gastric submucosa space may be an ideal site for islet transplantation; however, whether pro-inflammation factors mediated islet dysfunction could be avoided or alleviated is still unclear. METHODS: Islets of Sprague Dawley (SD) rat were transplanted into the streptozotocin-induced diabetic SD rats. Transplantation sites included gastric submucosa (GS), intraportal vein (PV) and kidney capsule (KC), and the efficiency of glycemic control and site-specific differen...
Source: Transplant Immunology - April 14, 2020 Category: Transplant Surgery Authors: Yin Z, Li J, Zheng Y, Wang S, Wang X Tags: Transpl Immunol Source Type: research

High expression of granzyme B in conventional CD4+ T cells is associated with increased relapses after allogeneic stem cells transplantation in patients with hematological malignancies.
Abstract Granzyme B is known to be a serine protease contained in granules of cytotoxic T cells. We have previously reported an influence of granzyme B expression in T regulatory cells (Tregs) on the risk of acute graft versus host disease (GVHD) onset. However, it is still unknown if conventional T cells (Tcon) use the granzyme B pathway as a mechanism of alloimmunity. We hypothesized that granzyme B in Tcon may affect recurrence within the first 6 months after allogeneic transplantation (allo-HSCT). A total of 65 patients with different hematological malignancies were included in this study. Blood samples were...
Source: Transplant Immunology - April 14, 2020 Category: Transplant Surgery Authors: Drokov M, Davydova Y, Popova N, Kapranov N, Starikova O, Mikhaltsova E, Nareyko M, Dmitrova A, Konova Z, Galtseva I, Kuzmina L, Parovichnikova E, Savchenko V Tags: Transpl Immunol Source Type: research

Reduced CD4+ CD25++ CD45RA- Foxp3hi activated regulatory T cells and its association with acute rejection in patients with kidney transplantation.
CONCLUSION: Patients with AR had poorer immunoregulatory properties than those with normal graft functioning, as well as those in the control group. These reduced immunoregulatory properties in patients with AR could lead to graft rejection. PMID: 32240775 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - March 30, 2020 Category: Transplant Surgery Authors: Mirzakhani M, Shahbazi M, Akbari R, Oliaei F, Asgharpour M, Nikoueinejad H, Mohammadnia-Afrouzi M Tags: Transpl Immunol Source Type: research

Dialysis therapy is associated with peripheral marginal zone B-cell augmentation.
In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in pre-emptive (never experienced dialysis) and dialysis cohorts. There was difference in circulating marginal zone B cells (MZB) (IgDhighCD27high) between dialysis patients and those receiving kidney grafts pre-emptively (P = .002). Patients treated on dialysis>12 months had also 4.2-fold greater risk of increased absolute numbers of MZB (95%CI:1.6-11.2; P = .004). Ther...
Source: Transplant Immunology - March 27, 2020 Category: Transplant Surgery Authors: Stranavova L, Hruba P, Slatinska J, Sawitzki B, Reinke P, Volk HD, Viklicky O Tags: Transpl Immunol Source Type: research

Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis.
CONCLUSION: The NCR+-ILC3/IL-22 axis is impaired during ACR contributing to a delay in or lack of a complete and efficient epithelial regeneration. Thus, our findings reveal that IL-22 analogues could potentially be used as a new complementary therapeutic approach, in conjunction with immunosuppressant drugs, in order to promote mucosal regeneration upon ACR. PMID: 32209429 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - March 21, 2020 Category: Transplant Surgery Authors: Melisa PM, Virginia GP, Carolina R, Claudia F, Carlos L, Fabio N, Martín R, Gondolesi Gabriel E, Dominik M Tags: Transpl Immunol Source Type: research

The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation: A case series.
s M Abstract BACKGROUND: The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA. METHODS: From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodi...
Source: Transplant Immunology - March 16, 2020 Category: Transplant Surgery Authors: Daniëls L, Claas FHJ, Kramer CSM, Senev A, Vanden Driessche M, Emonds MP, Van Laecke S, Hellemans R, Abramowicz D, Naesens M Tags: Transpl Immunol Source Type: research

A potential role of neutrophil extracellular traps (NETs) in kidney acute antibody mediated rejection.
CONCLUSIONS: KTR show enhanced NETosis. This may indicate a permanent activation of neutrophils. Although more studies are needed, the higher amount of NETs and netting neutrophils in biopsies of KTR-Cases suggest a role of NETosis in AAMR. PMID: 32156665 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - March 7, 2020 Category: Transplant Surgery Authors: Torres-Ruiz J, Villca-Gonzales R, Gómez-Martín D, Zentella-Dehesa A, Tapia-Rodríguez M, Uribe-Uribe NO, Morales-Buenrostro LE, Alberú J Tags: Transpl Immunol Source Type: research

Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates.
In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions...
Source: Transplant Immunology - March 3, 2020 Category: Transplant Surgery Authors: Timofeeva OA, Alvarez R, Pelberg J, Yoon E, Alsammak M, Geier SS, Ruggia-Check C, Hassler J, Hoosain J, Brisco MA, Afari-Armah N, Rakita V, Brann S, Keshavamurphy S, Gomez-Abraham J, Minakata K, Toyoda Y, Hamad E Tags: Transpl Immunol Source Type: research

Epithelial-mesenchymal transition and membrane microparticles: Potential implications for bronchiolitis obliterans syndrome after lung transplantation.
ler R Abstract Long term survival post lung transplantation (LTx) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). One mechanism involved is the epithelial-mesenchymal transition (EMT). Membrane microparticles (MPs) are known to be involved in some respiratory diseases and in other organs allograft rejection episodes. We hypothesized that leukocyte-derived MPs likely contribute to EMT. To emphasize this physiological concept, our objectives were to: (1) confirm the presence of EMT on explanted lungs from patients who underwent a second LTx for BOS; 2) characterize circulating MPs in transpl...
Source: Transplant Immunology - February 22, 2020 Category: Transplant Surgery Authors: Renaud-Picard B, Vallière K, Toussaint J, Kreutter G, El-Habhab A, Kassem M, El-Ghazouani F, Olland A, Hirschi S, Porzio M, Chenard MP, Toti F, Kessler L, Kessler R Tags: Transpl Immunol Source Type: research

Exploring predicted indirectly recognizable HLA epitopes (PIRCHE-II) in liver transplant recipients on calcineurin inhibitor-free maintenance immunosuppression. A retrospective single center study.
ux GP Abstract The PIRCHE (Predicted Indirectly ReCognizable HLA Epitopes) score is an HLA epitope matching algorithm. PIRCHE algorithm estimates the level of presence of T-cell epitopes in mismatched HLA. The PIRCHE-II numbers associate with de novo donor-specific antibody (dnDSA) formation following liver transplantation and kidney allograft survival following renal transplantation. The aim of our study was to assess the PIRCHE-II score in calcineurin inhibitor (CNI)-free maintenance immunosuppression recipients. This was a retrospective study of forty-one liver transplant recipients on CNI-free immunosuppressio...
Source: Transplant Immunology - February 12, 2020 Category: Transplant Surgery Authors: Meszaros M, Niemann M, Bedoya JU, Faure S, Meunier L, Rivière B, Costes-Martineau V, Thevenin C, Pageaux GP Tags: Transpl Immunol Source Type: research

Pre-existing self-reactive IgA antibodies associated with primary graft dysfunction after lung transplantation.
CONCLUSION: Pre-existing IgG and IgA autoantibodies in LT patients correlate with PGD and with survival in a single center, small cohort of lung transplant recipients. Further validation is needed to confirm the findings in the study. PMID: 32007544 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - January 30, 2020 Category: Transplant Surgery Authors: Kaza V, Zhu C, Feng L, Torres F, Bollineni S, Mohanka M, Banga A, Joerns J, Mohanakumar T, Terada LS, Li QZ Tags: Transpl Immunol Source Type: research

Combined treatment with vitamin D3 and antibody agents suppresses secondary heart transplant rejection in the early postoperative period.
CONCLUSION: Vitamin D3 administered as an immunosuppressive agent, when combined with monoclonal antibody treatment, may protect heart grafts from memory T cell responses in a secondary heart transplant model. PMID: 31953155 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - January 14, 2020 Category: Transplant Surgery Authors: Xie B, Ma Y, Xi Y, Di A, Chen X, Chen Y, Zhang L, Xu S, Wang C, Yan G, Qi Z Tags: Transpl Immunol Source Type: research

Receptor activator of the NF κB ligand system protects renal function during experimental renal ischemia-reperfusion in mice.
Receptor activator of the NFκB ligand system protects renal function during experimental renal ischemia-reperfusion in mice. Transpl Immunol. 2020 Jan 03;:101263 Authors: Nakayama A, Isoyama N, Yamamoto T, Nagata Y, Matsumura M, Fujikawa K, Matsuyama H, Shiraishi K Abstract Renal ischemia-reperfusion (I/R) injury is closely associated with delayed graft function and poor long-term graft survival following transplantation. Various pathophysiologies can cause the deterioration of renal function; however, the immune system plays important roles in promoting and protecting renal tissues. Receptor ac...
Source: Transplant Immunology - January 3, 2020 Category: Transplant Surgery Authors: Nakayama A, Isoyama N, Yamamoto T, Nagata Y, Matsumura M, Fujikawa K, Matsuyama H, Shiraishi K Tags: Transpl Immunol Source Type: research

Prospective validation of the L-index reflecting both the intensity and duration of lymphopenia and its detailed evaluation using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation.
Abstract We prospectively validated the previously reported L-index, which reflects both the intensity and duration of lymphopenia, and further evaluated it using a lymphocyte subset analysis after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 30). The L-index was defined as the area over the lymphocyte curve during lymphopenia (3 cells/2 slides by the C10/11 method in 21 cases (CMV-AG ≥3 group) at a median of 34 days. L-index(30) was significantly higher in the CMV-AG ≥3 group than in the CMV-AG
Source: Transplant Immunology - December 30, 2019 Category: Transplant Surgery Authors: Kimura SI, Sato M, Misaki Y, Yoshimura K, Gomyo A, Hayakawa J, Akahoshi Y, Harada N, Tamaki M, Kusuda M, Kameda K, Wada H, Kawamura K, Terasako-Saito K, Kikuchi M, Tanihara A, Nakasone H, Kako S, Kanda Y Tags: Transpl Immunol Source Type: research

An in vitro model of antibody-mediated injury to glomerular endothelial cells: Upregulation of MHC class II and adhesion molecules.
Abstract Chronic active antibody-mediated rejection is a major cause of allograft failure in kidney transplantation. Microvascular inflammation and transplant glomerulopathy are defining pathologic features of chronic active antibody-mediated rejection and are associated with allograft failure. However, the mechanisms of leukocyte infiltration and glomerular endothelial cell injury remain unclear. We hypothesized MHC class II ligation on glomerular endothelial cells (GEnC) would result in upregulation of adhesion molecules and production of chemoattractants. A model of endothelial cell activation in the presence o...
Source: Transplant Immunology - December 27, 2019 Category: Transplant Surgery Authors: Wilson NA, Dylewski J, Degner KR, O'Neill MA, Reese SR, Hidalgo LG, Blaine J, Panzer SE Tags: Transpl Immunol Source Type: research

TLR2 and NODs1 and 2 cooperate in inflammatory responses associated with renal ischemia reperfusion injury.
This study examined the relative roles of TLR2 and NODs 1 and 2 in activation of myeloid cells that contribute to inflammation after renal IRI. We found that TLR2 and NOD1 and 2 signaling induces neutrophil, macrophage and dendritic cell migration in vitro, however their blockade only decreases neutrophil infiltration into ischemic kidneys. The results of this study suggest that future therapies targeted to innate immune blockade should consider that either TLR2 or NOD1/2 blockade could decrease neutrophil inflammation following an ischemic insult to the kidney, however blockade of these PRRs would not likely impact infilt...
Source: Transplant Immunology - November 21, 2019 Category: Transplant Surgery Authors: Kasmisetty SG, Hawkes A, Barekatain K, Soo E, Welch AK, McKay DB Tags: Transpl Immunol Source Type: research

Identification of the immunological profile in rejection-free heart transplantation.
CONCLUSION: In conclusion, we defined the immune status of pre-HTx patients and the target immunological profile of LT-HTx patients. These data may help to establish a monitoring tool that is based on a multiparametric dataset. PMID: 31704267 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - November 5, 2019 Category: Transplant Surgery Authors: Klaeske K, Lehmann S, Büttner P, Palitzsch R, Fischer J, Jawad K, Garbade J, Borger MA, Barten MJ, Dieterlen MT Tags: Transpl Immunol Source Type: research

Effects of recombinant thrombomodulin on long-term prognosis after allogeneic hematopoietic stem cell transplantation.
Abstract We investigated the effects of early recombinant thrombomodulin (rTM) treatment on long-term prognosis after hematopoietic stem cell transplantation (HSCT). Subjects included 300 patients who underwent allogeneic HSCT (131 in the rTM(+) group and 169 in the rTM(-) group). The control group received heparin or no anti-coagulation therapy. When we examined patients with confirmed complications (day 1-100), the frequencies of acute graft-versus-host disease (aGVHD) and thrombotic microangiopathy (TMA) were significantly lower in the rTM(+) group, while the frequencies of veno-occlusive disease did not show s...
Source: Transplant Immunology - October 26, 2019 Category: Transplant Surgery Authors: Nomura S, Konishi A, Tsubokura Y, Azuma Y, Hotta M, Yoshimura H, Nakanishi T, Fujita S, Satake A, Katayama Y, Ohta S, Hayashi K, Ishii K, Ito T Tags: Transpl Immunol Source Type: research

Impact of immunosuppressive therapy on brain derived cytokines after liver transplantation.
n K Abstract BACKGROUND: While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT). METHODS: Levels of T cell-mediated cytokines (e.g. Interferon-γ (IFN-γ)) and brain-derived cytokines (e.g. brain derived neurotrophic factor...
Source: Transplant Immunology - October 24, 2019 Category: Transplant Surgery Authors: Dirks M, Pflugrad H, Tryc AB, Schrader AK, Ding X, Lanfermann H, Jäckel E, Schrem H, Beneke J, Barg-Hock H, Klempnauer J, Falk CS, Weissenborn K Tags: Transpl Immunol Source Type: research

Strategies to achieve immune tolerance in allogeneic solid organ transplantation.
Abstract Organ transplantation is an effective way to treat many end-stage diseases. In order to overcome post-transplant rejection, immunosuppressive agents have been widely used, but the long-term survival of transplanted organs still has not been achieved in the clinic. For decades, tolerance is the "holy grail" that transplant immunologists have longed for. The well-known approaches to induce immune tolerance are through adoptively transferred regulatory T cells and achieving chimeric states. In addition, there are a variety of promising potential strategies, including costimulatory blockade, regulat...
Source: Transplant Immunology - October 23, 2019 Category: Transplant Surgery Authors: Zeng S, Xiao Z, Wang Q, Guo Y, Yvnan H, Zhu Q, Zou Y Tags: Transpl Immunol Source Type: research

Profiles of B-cell subsets in immunologically stable renal allograft recipients and end-stage renal disease patients.
CONCLUSIONS: The percentages of the total, transitional, Breg, PCs, MZ, and UM B-cell subsets in immunologically stable renal allograft recipients were significantly different from healthy controls. However, B-cell subsets in patients with ESRD were minimally different with immunologically stable renal allograft recipients. PMID: 31626945 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - October 15, 2019 Category: Transplant Surgery Authors: Zhuang Q, Li H, Yu M, Peng B, Liu S, Luo M, Stefano GB, Kream RM, Ming Y Tags: Transpl Immunol Source Type: research

Peripheral CD19+CD24highCD38high B-regulatory cells in lung transplant recipients.
Abstract BACKGROUND: The role of CD19+CD24highCD38high B-regulatory cells in solid-organ Transplant (Tx) in acceptance are still scarce. In previous studies on kidney transplant recipients may suggest a protective role of this cell subtype in graft tolerance and the existence of a cross talk between B-and T-regulatory clones. In lung transplantation, the role of B-regulatory cells has never been investigated. In a murine tracheal transplantation model, this subset seems able to prevent tracheal obliteration when in combination with rapamycin. Aim of this study is to analyze peripheral CD19+CD24highCD38high B-reg c...
Source: Transplant Immunology - September 14, 2019 Category: Transplant Surgery Authors: Davide P, Monica M, Sara M, Alice B, Simona I, Emanuela C, Oggionni T, Vanessa F, Laura P, Luigia S, Federica M Tags: Transpl Immunol Source Type: research

FK506 combined with GM6001 prevents tracheal obliteration in a mouse model of heterotopic tracheal transplantation.
In this study, we investigated the effect of tacrolimus (FK506) combined with GM6001,a matrix metalloproteinase (MMP) inhibitor, on the formation of OB using a mouse heterotopic tracheal transplantation model. METHODS: Syngeneic tracheal grafts were transplanted heterotopically from BALB/c mice to BALB/c mice. Allografts from C57BL/6 mice were transplanted to BALB/c mice. Isograft group, allograft group, allograft+FK506 group, allograft +GM6001 group and allograft+FK506 + GM6001 group was given respectively intraperitoneal injection of saline, saline, FK506, GM6001 and FK506 + GM6001 once a day. At 28 da...
Source: Transplant Immunology - September 14, 2019 Category: Transplant Surgery Authors: Li Y, Shu P, Tang L, Yang X, Fan J, Zhang X Tags: Transpl Immunol Source Type: research

The effect of a novel immunosuppressive drug, a PAK-2 inhibitor, on macrophage differentiation/polarization in a rat small intestinal transplantation model.
In this study, we investigated the function of this drug mainly on macrophages using a rat small intestinal transplant model. METHODS: Male Dark Agouti (DA) and Lewis rats (LEW), 7-9 weeks of age, were used as donor and recipient, respectively. Approximately 15 cm intestinal grafts were heterotopically transplanted to the recipient rats. The recipient rat was treated with PQA-18 (4 mg/kg/per day) by intraperitoneal injection (ip) from postoperative day 1 for 2 weeks. The in vivo effects of this drug were evaluated based on changes in body weight, and the population of each type of blood cell. Mixed lymphocyte ...
Source: Transplant Immunology - September 14, 2019 Category: Transplant Surgery Authors: Kodama T, Maeda A, Lo PC, Noguchi Y, Toyama C, Takama Y, Ueno T, Tazuke Y, Eguchi H, Matsunami K, Miyagawa S, Okuyama H Tags: Transpl Immunol Source Type: research

Human CTLA4-Ig therapy can give false-positive anti-pig antibody results in primates after xenotransplantation.
Abstract BACKGROUND: Measurement of serum anti-pig antibodies is an important parameter in immune monitoring after pig-to-nonhuman primate xenotransplantation. Pig aortic endothelial cells (pAECs) are commonly used for this purpose. However, human (h) CTLA4-Ig (abatacept/belatacept) could bind to pCD80/86 on the cells, and a secondary antibody (i.e., anti-human IgG) may recognize hCTLA4-Ig (in the absence of serum anti-pig IgG antibody binding to pAECs), potentially leading to misinterpretation of the results. Our aim was to determine whether hCTLA4-Ig binding to pAECs is associated with false-positive results. ...
Source: Transplant Immunology - August 28, 2019 Category: Transplant Surgery Authors: Li Q, Yamamoto T, Iwase H, Nguyen HQ, Wang Y, Ayares D, Cooper DKC, Hara H Tags: Transpl Immunol Source Type: research

The effect of oral melatonin on renal ischemia-reperfusion injury in transplant patients: A double-blind, randomized controlled trial.
Abstract BACKGROUND: One of the important factors in the occurrence of acute kidney injury (AKI) among renal transplant patients (RTPs) is ischemia reperfusion injury (IRI). The current study aimed at determining the anti-inflammatory and anti-oxidative effects of melatonin on the complications of IRI and the level of Klotho expression in these patients. METHODS: A total of 40 renal transplant candidates were randomly assigned into placebo or melatonin group receiving the same dose of 3 mg/day. In order to measure serum melatonin levels, inflammatory and oxidative stress factors, renal function biomarkers, ...
Source: Transplant Immunology - August 22, 2019 Category: Transplant Surgery Authors: Panah F, Ghorbanihaghjo A, Argani H, Haiaty S, Rashtchizadeh N, Hosseini L, Dastmalchi S, Rezaeian R, Alirezaei A, Jabarpour M, Ahmad SNS, Sanajoo D Tags: Transpl Immunol Source Type: research

Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model.
Abstract Ischemia-reperfusion injury (IRI) after lung transplantation mainly contributes to the development of primary graft dysfunction. The Sprouty-related EVH1-domain-containing (SPRED) protein family inhibits the mitogen activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway. Our study was aimed at examining the role of SPRED2 in IRI in mice that received orthotopic lung transplantation. Syngeneic mouse lung transplantation was performed in wild-type C57BL/6 J (WT) mice and Spred2 knockout (Spred2-/-) mice on the C57BL/6 J background from the WT donor. Four hours after reperfusio...
Source: Transplant Immunology - August 22, 2019 Category: Transplant Surgery Authors: Hashimoto K, Yamane M, Sugimoto S, Hirano Y, Kurosaki T, Otani S, Miyoshi K, Ohara T, Okazaki M, Yoshimura T, Oto T, Matsukawa A, Toyooka S Tags: Transpl Immunol Source Type: research

Prognostic value of C3d-fixing, preformed donor-specific antibodies in crossmatch-positive living kidney transplantation.
Abstract The occurrence of acute antibody-mediated rejection (ABMR) is higher in flow cytometric crossmatch (FCXM)-positive patients despite desensitization. Accumulating evidence suggests a correlation between the complement-binding ability of donor-specific antibodies (DSAs) and the risk of ABMR. Here, we investigated the correlation between complement C3d-fixing ability of preformed DSA and ABMR risk, the efficacy of a desensitization protocol for patients with C3d-fixing DSA, and the risk of ABMR in 21 DSA- and FCXM-positive patients. We retrospectively analyzed the C3d-fixing ability and mean fluorescence int...
Source: Transplant Immunology - August 6, 2019 Category: Transplant Surgery Authors: Miyake K, Okumi M, Kakuta Y, Unagami K, Furusawa M, Ishida H, Tanabe K Tags: Transpl Immunol Source Type: research

Immunoglobulin abnormalities in 1677 solid organ transplant recipients. Implications for posttransplantation follow-up.
CONCLUSIONS: GP after SOT is associated with a high risk of PTLD, allograft loss and poor survival. The combination of SPE, SIFE, SFLC and UIFE is optimal for GP detection. These methods aid in identifying patients who are at risk for PTLD or allograft damage and should be included in regular post-Tx follow-up. PMID: 31398462 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - August 6, 2019 Category: Transplant Surgery Authors: Sečník P, Jabor A, Lavríková P, Sečník J, Malíková P, Pokorná E, Franeková J Tags: Transpl Immunol Source Type: research

Suppressor of cytokine signaling genes in renal transplant receivers: Association with transplant fate.
Abstract Suppressor of cytokine signaling (SOCS) proteins have acknowledged roles in regulation of immune responses. Moreover, their role in the evolution of allograft rejection is being elucidated. In the current investigation, we measured transcript levels of SOCS1-4 in the peripheral blood of a group of renal transplant recipients including both rejected and non-rejected allografts. Expression analyses showed that relative expression of SOCS2 was significantly higher in transplant-rejected male patients compared to non-rejected group. However, such significant difference was not detected between female subjects...
Source: Transplant Immunology - August 6, 2019 Category: Transplant Surgery Authors: Nafar M, Kalantari S, Omrani MD, Samavat S, Arsang-Jang S, Taheri M, Ghafouri-Fard S Tags: Transpl Immunol Source Type: research

Tacrolimus exposure after liver transplantation for alcohol-related liver disease: Impact on complications.
Abstract BACKGROUND: Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). For 20 years, tacrolimus (Tac) is the cornerstone immunosuppressive drug used after LT and is very efficient for the prevention of rejection. Nevertheless, the major drawback of long-term use of Tac is the risk for developing dose-dependent adverse effects. OBJECTIVE: The aim of the present study was to assess the impact of Tac exposure (trough concentrations and concentration/dose (C/D) ratio) during the first year after LT, on short- and long-term complications after LT for ALD. MET...
Source: Transplant Immunology - July 24, 2019 Category: Transplant Surgery Authors: Bardou FN, Guillaud O, Erard-Poinsot D, Chambon-Augoyard C, Thimonier E, Vallin M, Boillot O, Dumortier J Tags: Transpl Immunol Source Type: research

Low dose valganciclovir as cytomegalovirus prophylaxis in post-renal transplant recipients induced with alemtuzumab: A single-center study.
CONCLUSION: In this institution's experience, CMV incidence was reduced compared to historically reported data by using low-dose (450 mg) VGCV prophylaxis in combination with Ale induction and steroid minimization. However, overall rejection rate was significantly higher in our population, possibly influenced by the degree of steroid minimization. PMID: 31344441 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - July 22, 2019 Category: Transplant Surgery Authors: Korneffel K, Mitro G, Buschor K, Rees M, Ortiz J Tags: Transpl Immunol Source Type: research

Preliminary assessment of the feasibility of autologous myeloid-derived suppressor cell infusion in non-human primate kidney transplantation.
Abstract Myeloid-derived suppressor cells (MDSC) are a heterogenous population of immunosuppressive myeloid cells now considered important immune regulatory cells in diverse clinical conditions, including cancer, chronic inflammatory disorders and transplantation. In rodents, MDSC administration can inhibit graft-versus-host disease lethality and enhance organ or pancreatic islet allograft survival. There is also evidence, however, that under systemic inflammatory conditions, adoptively-transferred MDSC can rapidly lose their suppressive function. To our knowledge, there are no reports of autologous MDSC administr...
Source: Transplant Immunology - July 19, 2019 Category: Transplant Surgery Authors: Ezzelarab MB, Perez-Gutierrez A, Humar A, Wijkstrom M, Zahorchak AF, Lu-Casto L, Wang YC, Wiseman RW, Minervini M, Thomson AW Tags: Transpl Immunol Source Type: research

Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.
CONCLUSIONS: This study demonstrated that col.(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD. PMID: 31325493 [PubMed - as supplied by publisher] (Source: Transplant Immunology)
Source: Transplant Immunology - July 17, 2019 Category: Transplant Surgery Authors: Zaffiri L, Shah RJ, Stearman RS, Rothhaar K, Emtiazjoo AM, Yoshimoto M, Fisher AJ, Mickler EA, Gartenhaus MD, Cohort LTOG, Diamond JM, Geraci MW, Christie JD, Wilkes DS Tags: Transpl Immunol Source Type: research