scholarly journals Set Up for Failure: Pre-Existing Autoantibodies in Lung Transplant

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander McQuiston ◽  
Amir Emtiazjoo ◽  
Peggi Angel ◽  
Tiago Machuca ◽  
Jason Christie ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Pulmonary Disease ◽  
Lung Transplant ◽  
Survival Rates ◽  
Hla Antigens ◽  
Solid Organ ◽  
Term Survival ◽  
Transplant Patients ◽  
Set Up

Lung transplant patients have the lowest long-term survival rates compared to other solid organ transplants. The complications after lung transplantation such as primary graft dysfunction (PGD) and ultimately chronic lung allograft dysfunction (CLAD) are the main reasons for this limited survival. In recent years, lung-specific autoantibodies that recognize non-HLA antigens have been hypothesized to contribute to graft injury and have been correlated with PGD, CLAD, and survival. Mounting evidence suggests that autoantibodies can develop during pulmonary disease progression before lung transplant, termed pre-existing autoantibodies, and may participate in allograft injury after transplantation. In this review, we summarize what is known about pulmonary disease autoantibodies, the relationship between pre-existing autoantibodies and lung transplantation, and potential mechanisms through which pre-existing autoantibodies contribute to graft injury and rejection.

Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection

2004 ◽  
Vol 286 (6) ◽  
pp. L1129-L1139 ◽  
Author(s):  
Tina L. Sumpter ◽  
David S. Wilkes
Keyword(s):  
Lung Transplantation ◽  
Lung Transplant ◽  
Transplant Rejection ◽  
Survival Rates ◽  
Definitive Treatment ◽  
Solid Organ ◽  
Type V Collagen ◽  
End Stage ◽  
Type V

Lung transplantation is the only definitive treatment modality for many forms of end-stage lung disease. However, the lung is rejected more often than any other type of solid organ allograft due to chronic rejection known as bronchiolitis obliterans (BO). Indeed, BO is the primary reason why the 5- and 7-yr survival rates are worse for the lung than for any other transplanted organ. Alloimmunity to donor antigens is established as the primary mechanism that mediates rejection responses. However, newer immunosuppressive regimens designed to abrogate alloimmune activation have not improved survival. Therefore, these data suggest that other antigens, unrelated to donor transplantation antigens, are involved in rejection. Utilizing human and rodent studies of lung transplantation, our laboratory has documented that a native collagen, type V collagen [col(V)], is a target of the rejection response. Col(V) is highly conserved; therefore, these data indicate that transplant rejection involves both alloimmune and autoimmune responses. The role of col(V) in lung transplant rejection is described in this review article. In addition, the potential role of regulatory T cells that are crucial to modulating autoimmunity and alloimmunity is also discussed.

Antibody-Mediated Rejection and Lung Transplantation

2021 ◽  
Vol 42 (03) ◽  
pp. 428-435
Author(s):  
Laura P. Halverson ◽  
Ramsey R. Hachem
Keyword(s):  
Lung Transplantation ◽  
Diagnostic Criteria ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Solid Organ ◽  
Term Survival ◽  
Antibody Mediated Rejection ◽  
History Of ◽  
Active Research

AbstractAntibody-mediated rejection (AMR) is now a widely recognized form of lung allograft rejection, with mounting evidence for AMR as an important risk factor for the development of chronic lung allograft dysfunction and markedly decreased long-term survival. Despite the recent development of the consensus diagnostic criteria, it remains a challenging diagnosis of exclusion. Furthermore, even after diagnosis, treatment directed at pulmonary AMR has been nearly exclusively derived from practices with other solid-organ transplants and other areas of medicine, such that there is a significant lack of data regarding the efficacy for these in pulmonary AMR. Lastly, outcomes after AMR remain quite poor despite aggressive treatment. In this review, we revisit the history of AMR in lung transplantation, describe our current understanding of its pathophysiology, discuss the use and limitations of the consensus diagnostic criteria, review current treatment strategies, and summarize long-term outcomes. We conclude with a synopsis of our most pressing gaps in knowledge, introduce recommendations for future directions, and highlight promising areas of active research.

scholarly journals The role of autoimmunity in obliterative bronchiolitis after lung transplantation

2013 ◽  
Vol 304 (5) ◽  
pp. L307-L311 ◽  
Author(s):  
Daniel J. Weber ◽  
David S. Wilkes
Keyword(s):  
Lung Transplantation ◽  
Lung Transplant ◽  
Transplant Rejection ◽  
Survival Rates ◽  
Bronchiolitis Obliterans Syndrome ◽  
Obliterative Bronchiolitis ◽  
Definitive Treatment ◽  
Limiting Factor ◽  
Solid Organ

First performed in the 1960s with long-term successes achieved in the 1980s, lung transplantation remains the only definitive treatment option for end-stage lung disease. Chronic lung rejection, pathologically classified as obliterative bronchiolitis (OB) with its clinical correlate referred to as bronchiolitis obliterans syndrome, is the limiting factor than keeps 5-yr survival rates for lung transplant significantly worse than for other solid organ transplants. Initially, OB was largely attributed to immune responses to donor antigens, alloimmunity. However, more recent work has demonstrated the role of autoimmunity in the process of lung transplant rejection. IL-17 and autoantigens such as collagen type V and K-α1 tubulin have been implicated in the development of chronic rejection. Ultimately, this translational review discusses the role that autoimmunity plays in the development of OB and lung transplant rejection and then discusses options for therapeutic intervention.

Infections Within the First Month After Pediatric Lung Transplantation: Epidemiology and Impact on Outcomes

2020 ◽  
Author(s):  
Chinyere Onyearugbulem ◽  
Jorge Coss-Bu ◽  
Maria C Gazzaneo ◽  
Ernestina Melicoff ◽  
Shailendra Das ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Bacterial Infections ◽  
Lung Transplant ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Rank Test ◽  
P Value ◽  
Solid Organ ◽  
Care Hospital

Abstract Background Despite successes in lung transplantation, with infection as the leading cause of death in the first year following lung transplantation, there remains a lag in survival compared with other solid organ transplants. Infections that occur early after transplantation may impact short- and long-term outcomes in pediatric lung transplant recipients (LTRs). Methods We performed a retrospective review of pediatric LTRs at a large quaternary-care hospital from January 2009 to March 2016 to evaluate both epidemiologic features of infection in the first 30 days post-transplantation and mortality outcomes. The 30 days were divided into early (0–7 days) and late (8–30 days) periods. Results Among the 98 LTRs, there were 51 episodes of infections. Cystic fibrosis (CF) was associated with early bacterial infections (P = .004) while non-CF was associated with late viral (P = .02) infections. Infection after transplantation was associated with worse survival by Kaplan-Meier analysis (P value log rank test = .007). Viral infection in the late period was significantly associated with 3-year mortality after multivariable analysis (P = .02). Conclusions Infections in pediatric LTRs were frequent in the first 30 days after transplant, despite perioperative antimicrobial coverage. The association of 3-year mortality with late viral infections suggests a possible important role in post-transplant lung physiology and graft function. Understanding the epidemiology of early post-lung transplant infections can help guide post-operative management and interventions to reduce their incidence and the early- and long-term impact in this population.

Dose effects of cyclosporine and risk of cancer after heart transplantation

2017 ◽  
Vol 05 (01) ◽  
pp. 1-15
Keyword(s):  
Heart Transplantation ◽  
Treatment Options ◽  
Survival Rates ◽  
Solid Organ Transplantation ◽  
Solid Cancer ◽  
Solid Organ ◽  
Term Survival ◽  
Study Results ◽  
Risk Of Cancer

Cyclosporine is a potent immunosuppressant medication that is considered a disease modifying antirheumatic drug (DMARD) and used as treatment options after heart transplantation to improved long-term survival rates. The increased incidence of cancer after heart transplantation is well established in the literature, yet outcome studies of quantitative dose of cyclosporin related to cancer remains unclear. This prospective study was conducted between 1998 and 2013 and is based on 102 patients who had previously received heart transplant. The study results indicate that the average patient age was 65 years and the interval between transplantation and the appearance of solid cancer was 4.5 years (P < 0.002; OR = 2.02; 95% CI [1.59–2.29], P < 0.0002). However, the current study does draw much-needed attention to concerns about overall immunosuppressant exposure and its relationship to long-term outcomes after solid organ transplantation to reduce future cancer risk and more research for alternative drug level monitoring are important.

Malignancy following lung transplantation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12019-e12019
Author(s):  
Ammar Khanshour ◽  
Raed Abu Awwad ◽  
Robert Chapman ◽  
Alan Betensley
Keyword(s):  
Risk Factor ◽  
Skin Cancer ◽  
Lung Transplantation ◽  
Lung Transplant ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Chi Square ◽  
Post Transplant ◽  
Transplant Patients ◽  
Tertiary Center

e12019 Background: Malignancy has been shown to be a frequent complication of solid organ transplantation. It has been reported more commonly in lung transplant patients compared to other solid organ transplant recipients presumably due to the greater degree of immunosuppression required for these patients; the International Society for Heart and Lung Transplantation (ISHLT) reported that malignancies account for 15% of all deaths of lung transplant patients between 5 and 10 years after transplant. The aim of this study is to describe malignancies observed in patients who underwent lung transplantation in a single, large tertiary center. Methods: A retrospective analysis of the medical records of all adult recipients of lung allografts transplanted at Henry Ford Hospital between 1994 and 2010 was performed. Main variables included age at transplant, type of transplant, smoking status and type of malignancy. Study end point was development of malignancy. Patients surviving less than 3 months were excluded from the final analysis. T-test and Chi-square tests were used in the statistical analysis. Results: 145 patients received lung transplants with 136 patients surviving at least 3 months. Of the 136 cases included; 31 (23%) patients developed post-transplant malignancy as follows: skin cancer in 17, lung cancer (in the native lung) in 10, colon cancer in 3, cervical cancer in 3, renal cell carcinoma in 2, post transplant lymphoproliferative disorder (PTLD) in 2, head and neck cancer in 2, bladder cancer in 1 and vulvar cancer in 1. Eight patients developed more than one malignancy. 83% of those who developed malignancy were smokers while 67% of those who did not develop malignancy were smokers (Chi-square is 3.41, P>0.05). Patients who developed malignancy were older at time of transplantation (mean ± SD, 58.0±7.5 vs. 55.6±9.0 years; P= 0.04). Conclusions: Malignancy is a common complication after lung transplantation, with skin cancer being the most common. Age at transplantation seems to be a risk factor for development of malignancy. Smoking as a risk factor did not reach statistical significance in the studied population.

Transapical versus Conventional Aortic Valve Replacement�A Propensity-Matched Comparison

2012 ◽  
Vol 15 (1) ◽  
pp. 4 ◽  
Author(s):  
David M. Holzhey ◽  
William Shi ◽  
A. Rastan ◽  
Michael A. Borger ◽  
Martin H�nsig ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Survival Rates ◽  
Long Term Results ◽  
Term Survival ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Short And Long Term ◽  
Good Treatment Option ◽  
Matched Comparison

<p><b>Introduction:</b> The goal of this study was to compare the short- and long-term outcomes after aortic valve (AV) surgery carried out via standard sternotomy/partial sternotomy versus transapical transcatheter AV implantation (taTAVI).</p><p><b>Patients and Methods:</b> All 336 patients who underwent taTAVI between 2006 and 2010 were compared with 4533 patients who underwent conventional AV replacement (AVR) operations between 2001 and 2010. Using propensity score matching, we identified and consecutively compared 2 very similar groups of 167 patients each. The focus was on periprocedural complications and long-term survival.</p><p><b>Results:</b> The 30-day mortality rate was 10.8% and 8.4% (<i>P</i> = .56) for the conventional AVR patients and the TAVI patients, respectively. The percentages of postoperative pacemaker implantations (15.0% versus 6.0%, <i>P</i> = .017) and cases of renal failure requiring dialysis (25.7% versus 12.6%, <i>P</i> = .004) were higher in the TAVI group. Kaplan-Meier curves diverged after half a year in favor of conventional surgery. The estimated 3-year survival rates were 53.5% � 5.7% (TAVI) and 66.7% � 0.2% (conventional AVR).</p><p><b>Conclusion:</b> Our study shows that even with all the latest successes in catheter-based AV implantation, the conventional surgical approach is still a very good treatment option with excellent long-term results, even for older, high-risk patients.</p>

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

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