Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donor-lobar lung transplantation

Tanaka, Shin; Sugimoto, Seiichiro; Kurosaki, T.; Miyoshi, Kentaroh; Otani, Shinji; Suzawa, Ken; Hashida, Shinsuke; Yamane, Masaomi; Oto, Takahiro; Toyooka, Shinichi

doi:10.1038/s41598-018-33848-3

Cited by 26 publications

(22 citation statements)

References 30 publications

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“…For the differential diagnosis of CLAD, a blood examination, plain chest X-ray, computed tomography of the chest, 6-min walk test, electrocardiography, and echocardiography were also performed at the same time as the pulmonary function testing and Q-scinti. Transbronchial biopsy was not performed to diagnose CLAD after LDLLT to avoid unexpected bleeding or pneumothorax from the small lobar grafts 16 . The study protocol (No.…”

Section: Methodsmentioning

confidence: 99%

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation

Yamamoto

Sugimoto

Kurosaki

et al. 2020

Sci Rep

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Because chronic lung allograft dysfunction (cLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLt), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N = 27) and the non-CLAD group (N = 31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P < 0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P = 0.0037), the total lung capacity (P = 0.0028), and the forced vital capacity (P = 0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT. Recipients of lung transplantation (LT) still have a worse long-term survival than heart, liver, or kidney recipients 1-3. The recipients of LT mainly succumb to chronic lung allograft dysfunction (CLAD) 1-3 in the long term after both cadaveric LT and living-donor lobar lung transplantation (LDLLT) 4. For the diagnosis of CLAD after LDLLT, lung ventilation scintigraphy was previously shown to be beneficial using 133 Xe washout imaging 5. However, because 133 Xe was discontinued in 2016 and is no longer available in the world, a new diagnostic approach has been sought for CLAD after LDLLT. Lung perfusion scintigraphy (Q-scinti) has been shown to be valuable for the diagnosis of CLAD after single LT, as follows 6, 7. After single LT, Q-scinti normally shows a lung perfusion shift to the transplanted lung, rather than to the native lung, because of the lower vascular resistance of the graft; however, in patients developing CLAD after single LT, the perfusion decreases in the lung affected by CLAD, with a perfusion shift toward the native lung 6, 7. Interestingly, even in patients undergoing bilateral LDLLT, CLAD predominantly develops in a unilateral lung because in bilateral LDLLT, the lobar lung transplants are obtained from two different donors with different immunological backgrounds 4, 8. Therefore, we considered that in patients developing CLAD after bilateral LDLLT, Q-scinti could show a decrease in the perfusion of the lung affected by CLAD and a perfusion shift toward the contralateral unaffected lung. Our study evaluated the usefulness of Q-scinti in the diagnosis of CLAD, which is predominantly unilateral, in patients who have undergone bilateral...

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Section: Methodsmentioning

confidence: 99%

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation

Yamamoto

Sugimoto

Kurosaki

et al. 2020

Sci Rep

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“…Similar to the technology used in prenatal screening, circulation of donor DNA in the serum of recipients can be found after allograft injury with cell apoptosis. [73][74][75] Recent studies have identified ddcfDNA as an important biomarker associated with AMR, and assays for quantifying the amount of donor DNA have been developed, serving as a noninvasive method to screen for allograft injury. These assays have been shown to have excellent sensitivity for acute rejection but relatively poor specificity.…”

Section: Future Areas Of Developmentmentioning

confidence: 99%

Antibody-Mediated Rejection and Lung Transplantation

Halverson

Hachem

2021

Semin Respir Crit Care Med

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Antibody-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.

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“…The dPCR technique proved to be more sensitive in detection of relapse after allo-HSCT compared to qPCR [35]. Similarly to allo-HSCT, dPCR has also been widely used in the context of SOT to detect dd-cfDNA in combination with DIPs [32,50], SNPs [3], copy number variations [51], or HLA-disparities [17,18,43,52].…”

Section: Comparison Of Microchimerism Detection Techniquesmentioning

confidence: 99%

“…The latter consists mainly of small sized (around 150 base-pairs) double-stranded DNA fragments resulting from apoptosis, necrosis, immune-mediated cell damage, or release of nuclear DNA into the circulation predominantly from hematopoietic cells [2]. In the circulation, these fragments have a short half-life of approximately 1.5 h due to rapid hepatic and renal clearance [3].…”

Section: Introductionmentioning

confidence: 99%

Current Trends in Applications of Circulatory Microchimerism Detection in Transplantation

Andrikovics

Őrfi

Meggyesi

et al. 2019

IJMS

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Primarily due to recent advances of detection techniques, microchimerism (the proportion of minor variant population is below 1%) has recently gained increasing attention in the field of transplantation. Availability of polymorphic markers, such as deletion insertion or single nucleotide polymorphisms along with a vast array of high sensitivity detection techniques, allow the accurate detection of small quantities of donor- or recipient-related materials. This diagnostic information can improve monitoring of allograft injuries in solid organ transplantations (SOT) as well as facilitate early detection of relapse in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present review, genetic marker and detection platform options applicable for microchimerism detection are discussed. Furthermore, current results of relevant clinical studies in the context of microchimerism and SOT or allo-HSCT respectively are also summarized.

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Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donor-lobar lung transplantation

Cited by 26 publications

References 30 publications

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation

Antibody-Mediated Rejection and Lung Transplantation

Current Trends in Applications of Circulatory Microchimerism Detection in Transplantation

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