Clinical transplants最新文献

{"title":"Cytokines as Biomarkers for Renal Transplant Recipients: What is New?","authors":"Satoru Kawakita,&nbsp;Matthew J Everly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Poor long-term graft survival remains a major problem in the field of organ transplantation. This could be attributed at least in part, to the lack of reliable biomarkers that allow for accurate, noninvasive monitoring of graft status and individualized immunosuppressive therapy. To this end, cytokines and chemokines have been investigated in a number of studies to evaluate their potential to serve as diagnostic and prognostic markers for kidney transplantation. Based on our review of recent publications, urinary chemokine C-C motif ligand 2, chemokine C-XC motif ligand (CXCL) 9, and CXCL10 are identified as potential novel biomarkers of renal graft outcomes. Although there are numerous considerations to accurately analyze cytokine and chemokine profiles of transplant patients, continuing efforts in this field of research hold promise for improving the long-term outcomes of renal transplant recipients.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-HLA Antibodies in Clinical Transplantation.","authors":"Chitranon Chan-On,&nbsp;Minnie Sarwal","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Organ transplantation overcomes conservative therapy to improve patient longevity. Despite the improvement of donor-recipient compatibility tests and intensified immunosuppressive agents, long-term graft survival remains poor because of acute and chronic injury driven by immunologic and non-immunologic factors. The significant immunological barrier for graft longevity is antibody-mediated rejection. Antibodies reactive to donor-specific human leukocyte antigens (HLA) have been shown to have adverse effects on the transplanted organ. However, there is minimal or controversial data supporting a pathogenic effect of antibodies against non-HLAs. This review discusses non-HLA antibodies and relevant antigen targets that have been uncovered by molecular medicine and correspond with acute rejection and chronic allograft injury. Updated proteomic evaluation may improve our knowledge of the immune response by enhancing immunologic epitope determination outside the scope of HLA.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"45-61"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients.","authors":"Samir J Patel,&nbsp;Samantha A Kuten,&nbsp;Richard J Knight,&nbsp;Edward A Graviss,&nbsp;Duc Nguyen,&nbsp;A Osama Gaber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"103-109"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Outcomes in Intestinal Rehabilitation in Children.","authors":"Danielle Wendel,&nbsp;Simon P Horslen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Long-term outcomes for pediatric patients with intestinal failure have significantly improved with advances in management of parenteral nutrition and the associated comorbidities. These changes have been driven by the development of multidisciplinary intestinal rehabilitation teams. Overall survival and transplant-free survival rates have increased while the introduction of new management strategies has decreased complications such as central line infections and intestinal failure associated liver disease. Factors have been identified that aid in prediction of duration of parenteral nutrition and time to enteral autonomy. Close long-term monitoring of growth and early evaluation of development are needed as abnormalities in both areas are common. With the improved survival, an important focus going forward will be the study of and improvement in quality of life for both children with intestinal failure and their families.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Impact of Non-HLA Antibodies in Solid Organ Transplantation.","authors":"Kyle Freischlag,&nbsp;Meghan H Pearl,&nbsp;Eileen T Chambers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Antibody-mediated rejection in solid organ transplantation is associated with significant organ dysfunction and allograft loss. Donor-specific antibodies against human leukocyte antigens (HLAs) have been a major focus for research, clinical testing, and therapies. Recently, non-HLA autoantibodies to various endothelial antigens including angiotensin II type 1 receptor, endothelin-1 type A receptor, Major Histocompatibility Complex Class 1-Related Chain A, perlecan, and collagen V are emerging as both potential mediators of allograft dysfunction and targets for intervention. Incorporation of non-HLA antibodies into clinical practice is currently not standardized due to a lack of consensus regarding the pathogenic effects on the allograft. Treatment strategies for non-HLA antibodies are evolving and remain an area that warrants further investigation.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"31-43"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza Immunization and the Generation of Anti-HLA and Anti-MICA Antibodies in Patients with Renal Failure and in Kidney Transplant Recipients.","authors":"Lluvia Marino,&nbsp;Josefina Alberú,&nbsp;Luis E Morales-Buenrostro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of this study was to determine whether the influenza vaccine induces the development of anti-human leukocyte antigen (HLA) and anti-major histocompatibility complex class I - chain A (MICA) antibodies. We determined the presence or de novo development of anti-HLA and anti-MICA antibodies in 3 groups of patients vaccinated against influenza: A) 42 healthy adults; B) 40 end-stage kidney disease patients; C) 25 kidney transplant recipients; and, D) 22 healthy adults who refused vaccination. Serum samples per subject were obtained: prior to vaccination, one week after vaccination, and on a monthly basis for 6 months. They were analyzed by LABScreen® Single Antigen, Luminex. The proportions of de novo antibodies (anti-HLA and anti-MICA) in the 4 groups were 2.4%, 17.5%, 20%, and 0%, respectively. Some patients developed the antibodies later, unrelated to the vaccine. We found preformed antibodies (anti-HLA and anti-MICA) in 67%, 78%, 88%, and 27% of cases in groups A, B, C, and D, respectively. The presence of preformed antibodies was the only predictive factor for the development of de novo antibodies. In conclusion, the development of de novo anti-HLA and anti-MICA antibodies after an external stimulus other than HLA antigens is possible. However, not all cases can be attributed to the vaccine.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"161-171"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35047249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Relevance of Donor-Specific IgM Antibodies in HLA Incompatible Renal Transplantation: A Retrospective Single-Center Study.","authors":"Adarsh Babu,&nbsp;Avgi Andreou,&nbsp;David Briggs,&nbsp;Nithya Krishnan,&nbsp;Rob Higgins,&nbsp;Dan Mitchell,&nbsp;Tom Barber,&nbsp;Sunil Daga","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Immunoglobulin G (IgG) antibodies against donor human leukocyte antigens (HLA) are monitored in the pre-and post-transplant period due to their established role in predicting rejection and renal allograft survival. However, the role of immunoglobulin M (IgM) anti-HLA donor-specific antibodies (DSA) is not fully understood, especially in highly-sensitized patients undergoing direct transplantation. We designed this study to determine whether IgM DSA predicts rejection episodes and/or graft failure. Samples from 92 patients who had undergone HLA-antibody incompatible transplants were tested at 5 time points: days -8 (pre-plasmapheresis), 0, 7, 14, and 30 using Luminex microbead assay with ethylenediaminetetraacetic acid containing wash buffer (LABScreen®, One Lambda, Canoga Park, CA). IgM was defined positive if the mean fluorescence values were greater than 2000. Presence of pre- and post-transplant IgM was correlated with early antibody mediated rejection episodes (within 30 days post-transplantation) and graft failure. Statistical analyses were performed using SPSS IBM software. Graft survival estimates were death-censored. The presence of pre-transplant IgM DSA did not predict rejection (p=0.83) or graft failure (p=0.424). The post-transplant IgM DSA levels peaked at day 14 (similar to IgG DSA levels). Presence of IgM DSA post-transplant (de novo and resynthesis) was not associated with rejection (p=0.83). However, post-transplant IgM was associated with graft failure (p=0.037). This study shows additional testing of post-transplant IgM DSA over and above IgG is important as post-transplant IgM DSA is associated with graft failure.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"173-179"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35047250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Rejection, Kidney Allograft Function, and Graft Survival in Patients with Circulating Pre-Transplant IgG Antibodies Directed Against Donor HLA-A, -B, or -C Locus Determined Antigens.","authors":"Essa Abuhelaiqa,&nbsp;Rex Friedlander,&nbsp;Meredith Aull,&nbsp;Prabhakar Putheti,&nbsp;Vijay Sharma,&nbsp;Manikkam Suthanthiran,&nbsp;Darshana Dadhania","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The relationship between circulating pre-transplant immunoglobulin G (IgG) antibodies to donor human leukocyte antigen (HLA) -C locus determined antigens alone and acute rejection, kidney allograft function, and graft survival is not fully defined. Also, the impact of circulating pre-transplant IgG antibodies to donor HLA-C locus antigens alone on these outcomes has not been compared with the impact of circulating pre-transplant IgG antibodies to donor HLA-A or -B locus antigens. We conducted a retrospective review of records of 1252 kidney allograft recipients transplanted at our center between January 2010 and January 2016 to identify patients with circulating pre-transplant IgG antibodies directed at kidney donor HLA-A, -B, or -C locus determined antigens. Antibodies were detected and reported using the LABScreen Single Antigen Bead assay with microbeads coated with single HLA class I antigens. Pre-transplant and post-transplant data were collected and the graft outcomes of 16 kidney graft recipients with antibodies to HLA-C locus antigens were compared to the outcomes in 56 recipients with antibodies to HLA-A or -B locus determined antigens. The one-year acute rejection rate was 6% in those with donor-specific antibodies (DSA) to HLA-C locus antigens and 20% in those with DSA to HLA-A or -B locus antigens. The graft survival rate was 100% in those with DSA to HLA-C locus antigens and 95% in those with DSA to HLA-A or -B locus antigens. None of the numerical differences were statistically significant (p>0.05). The presence of circulating pre-transplant IgG antibodies directed at kidney donor HLA-C locus antigens alone may not be associated with an increased risk of acute rejection or a decreased graft survival rate. Our observations support the concept that circulating pre-transplant IgG antibodies directed at kidney donor HLA-C locus antigens alone do not negatively impact kidney allograft outcomes and that the mean fluorescence intensities of the antibodies directed at HLA-C locus alone should not be used to list unacceptable HLA-C locus antigens for kidney allocation. A study with a larger cohort is needed to investigate our hypothesis.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"83-91"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-transplant Desensitization for Deceased Donor Kidney Transplant Recipients: A Single Center Experience.","authors":"Dhiren Kumar,&nbsp;Hasan Fattah,&nbsp;Pamela M Kimball,&nbsp;Spencer LeCorchick,&nbsp;Felecia A McDougan,&nbsp;Anne L King,&nbsp;Gaurav Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The highly-sensitized kidney transplant candidate with no available living donors remains at a major disadvantage with decreased access and worse outcomes post-transplant. We have previously reported our initial data on both pre-transplant and post-transplant desensitization. We observed only a modest decline in unacceptable antigens with pretransplant intravenous immunoglobin (IVIG) and rituximab. Due to these observations, we have focused on a peri-operative post-transplant desensitization protocol in our program. Beginning in 2006, we implemented a simple point-based algorithm [variables included: panel reactive antibody (PRA) status; flow cytometric crossmatch (FCXM); and delayed graft function] to identify kidney transplant recipients who would undergo peri-operative plasmapheresis/IVIG to abrogate preformed antibody-mediated allograft rejection (AMR). Our previous results suggested acceptable 5-year outcomes. Here, in an expanded population (N=66), we report an overall death-censored graft survival of 73% at a mean follow-up of 8.5 years post-transplant. Our patients were largely African American (85%) and regrafts (39%), with a median PRA of 88%, and a mean T- and B-FCXM of 97 mean channel shifts (MCS) and 117 MCS, respectively. Although acute AMR rates were acceptable (12%), 22% of patients developed chronic AMR. A pre-transplant T-cell FCXM of > 200 MCS (p=0.02) or presence of donor specific antibodies (DSA) at most recent follow-up (p=0.02) were associated with graft loss. Current studies with revised protocols utilizing additional DSA information, surveillance biopsies, and proteasome inhibition are ongoing.</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"143-151"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35047247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA Epitopes and Shared Molecular Eplet Characterization and Their Implication on Transplant Outcome: The Experience of One Center.","authors":"Alexandre Bosch,&nbsp;Jorge Eguia,&nbsp;Francisco Boix,&nbsp;Manuela López,&nbsp;Gema González-Martinez,&nbsp;José A Galian,&nbsp;María R Moya-Quiles,&nbsp;Santiago Llorente,&nbsp;Manuel Muro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We report three interesting cases concerning antibody-mediated rejection (AMR), associated or not with anti-donor-specific antibodies, and detection of implicated molecular epitopes. The first report presents a case of intra-allele sensitization. The second case presents an interesting case concerning Luminex mean fluorescence intensity (MFI) levels considered to be low risk antibodies (<1000), but producing AMR. The third case occurred after a second kidney transplantation mediated by antibodies directed against HLA-C antigens (MFI<1000) in the previous transplantation (which was considered to be an indicator of low-risk of AMR).</p>","PeriodicalId":77074,"journal":{"name":"Clinical transplants","volume":"32 ","pages":"73-82"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35045317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}