The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Schmitz, Júlia; Kobbe, Guido; Kondakci, Mustafa; Schuler, Esther; Magorsch, Max; Adams, Ortwin

doi:10.1016/j.bbmt.2019.11.002

Cited by 26 publications

(50 citation statements)

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“…Here we report the results of a cohort of 168 patients transplanted in our center. As previously reported (31,32,34,37,42), we found that TTV titers increased rapidly after transplantation peaking at around 100 days post-HSCT, which corresponds to the time that IS is tapered. Moreover, donor CMV positive serostatus, donor type and immune suppression resulting from GVHD requiring systemic immunosuppression influenced the restoration of anti-TTV immunity.…”

Section: Discussionsupporting

confidence: 83%

“…In addition, they found that increasing TTV titers were associated with CMV/EBV reactivation but concluded that, owed to presence of the many transplant-related confounding factors such as conditioning, GVHD and IS, they could not be predictive of other immunerelated clinical complications. More recently, in a retrospective study, Schmitz et al (34) also investigated TTV as an early (before day 50) prognostic marker after HSCT but failed to show any association. Using multivariable analyses and cumulative FIGURE 6 | Occurrence of post-HSCT complications according to TTV level at d 100 post-HSCT.…”

Section: Discussionmentioning

confidence: 99%

“…For these reasons several studies assessed the quantification of TTV titers as a precise and straightforward method to measure the patient's immunity. TTV levels after solid organ transplantation (16)(17)(18)(19)(21)(22)(23)(24)(25)(26)(27) or HSCT (28)(29)(30)(31)(32)(33)(34) correlate with the intensity of immunosuppressive treatment and are associated with complications such as rejection (19, 21, 23-25, 35, 36), infections (18, 25-27, 33, 35) or GVHD (30)(31)(32)37).…”

Section: Introductionmentioning

confidence: 99%

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Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2020

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Impaired immune reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT) contributes to increased risk of cancer relapse and infection resulting in significant morbidity and mortality. Unfortunately, effective strategies to functionally assess the quality of immune reconstitution are still missing. Quantification of in vivo replication of the ubiquitous, non-pathogenic virus Torque Teno Virus (TTV) has been reported in small series as a test to functionally evaluate the quality of post-transplant immune reconstitution. In the present study, we analyzed by quantitative PCR TTV titers in plasma samples from a large cohort of 168 allogeneic HSCT recipients. Our analysis confirms that TTV titers peaked at 100 days post-transplant, followed by progressive normalization thereafter. Negative correlation of TTV titers with T cell absolute numbers during the first year post-transplant points to the restoration of an active anti-TTV immunity. Univariable and multivariable linear regression analysis demonstrated that donor CMV positive serostatus, donor type and immune suppression resulting from GVHD treatment affected the restoration of anti-TTV immunity. Importantly, higher TTV titers at 100 days after transplantation were associated with worse overall survival and higher risk of acute GVHD and infections. Our results provide new insights into the factors affecting the dynamics of TTV replication and indicate that TTV is a potentially useful biomarker to assess immune reconstitution and to predict complications and outcomes of allogeneic HSCT.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2020

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“…In line with these observations, the increase in cfDNA derived from DNA viruses was largely due to an increase in the burden of Anelloviridae cfDNA in the first months after HCT ( Fig. 4b ) 35 . Herpesviridae and Polyomaviridae frequently establish latent infection in adults and may reactivate after allogeneic HCT 36 .…”

Section: Resultssupporting

confidence: 79%

Cell-free DNA Profiling Informs Major Complications of Hematopoietic Cell Transplantation

Cheng

Loy

et al. 2020

Preprint

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14 15 16 17 ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) provides effective treatment for 18 hematologic malignancies and immune disorders. Monitoring for immune complications and infection is a 19 critical component of post-HCT therapy, however, current diagnostic options are limited. Here, we propose 20a blood test that employs genome-wide profiling of methylation marks comprised within circulating cell-21 free DNA to trace the tissues-of-origin of cell-free DNA (cfDNA), to quantify tissue-specific injury, and to 22 35 36More than 30,000 patients undergo allogeneic hematopoietic cell transplants (HCT) worldwide 37 each year for treatment of a variety of malignant and nonmalignant hematologic diseases 1-3 . However, 38 immune related complications occur frequently after HCT. Up to 50% of patients experience graft-versus-39host disease (GVHD) in the first year after transplantation. GVHD occurs when donor immune cells attack 40 the patient's own tissues 2,4-6 . Early and accurate diagnosis of GVHD is critical to inform treatment decisions 41and to prevent serious long-term complications, including organ failure and death. Unfortunately, there are 42 few, noninvasive diagnostic options that reliably identify patients very early after onset of GVHD 43 symptoms. In current clinical practice, diagnosis of GVHD relies almost entirely on clinical criteria and 44 often requires confirmation with invasive procedures, such as a biopsy of the gastrointestinal tract, skin, or 45 liver 7 . 46 47Small fragments of cell-free DNA (cfDNA) circulate in blood. In the absence of disease, cfDNA 48originates primarily from apoptosis of cells of the hematopoietic lineage 8 . During disease, a significant 49proportion of cfDNA can be derived from affected tissues 9-15 . In solid-organ transplantation (SOT), we and 50 others have shown that transplant donor derived cfDNA in the blood is a quantitative noninvasive marker 51 of solid organ transplant injury 12,13,16,17 . Here, we sought to investigate the utility of circulating cfDNA as a 52minimally invasive analyte to detect and quantify tissue injury due to GVHD after HCT. To quantify the 53 contributions of any tissue to the mixture of cfDNA in plasma, and thereby the degree of injury to any 54 vascularized tissue in the setting of HCT, we implemented shallow, whole genome bisulfite sequencing 55(WGBS) to profile 5-methylcytosine (5mC) marks of cfDNA. These marks are cell, tissue and organ type 56 specific 18 , and can inform the tissues-of-origin of cell-free DNA 8,11,19 . 57 58We collected serial blood samples from a prospective cohort of allogeneic HCT recipients at 59 predetermined time points before and after HCT. We analyzed a total of 106 plasma samples from 18 HCT 60 recipients with and without GVHD in the first 3 months post HCT. We observed rich dynamics in the tissue-61 origin of cfDNA in response to pre-transplant conditioning chemotherapy and following HCT. The tissue-62 origin of cfDNA after transplantation was patient-specific and a function of the ma...

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“…И, наконец, в последние годы рядом исследований показано, что TTV может служить эндогенным маркером иммунного статуса человека [170][171][172][173][174]. Дальнейшие исследования в этом направлении могут быть чрезвычайно полезны для практического здравоохранения.…”

Section: заключениеunclassified

Current Views of Torque Teno Virus (TTV) in Liver Diseases

Маев

Карлович

Burmistrov

et al. 2020

Rossijskij žurnal gastroènterologii, gepatologii, koloproktolog

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Цель обзора. Обзор посвящен анализу данных литературы по torque teno virus (вирус TT, TTV), открытому в конце XX столетия. Основные положения: TTV часто обнаруживают у пациентов с различными вирусными гепатитами, гепатитами без явного вирусного агента, а также у здорового населения. Имеются отдельные данные о биохимических и гистологических изменениях в ткани печени и эпителии желчных протоков при моноинфицировании TTV, подтверждающие возможность прохождения вирусом репликативного цикла в гепатоцитах. Наряду с этим при проведении гибридизации в клетках, пораженных вирусом ТТ, не было отмечено существенных цитопатических (повреждающих клетки) эффектов, характерных для патогенных гепатотропных вирусов. По мере изучения TTV происходила эволюция взглядов на роль вируса для человека. Первые представления о гепатотропности вируса постепенно изменялись по мере получения новых данных о распространенности вируса и его коинфекции с другими вирусами, в том числе вирусами известных гепатитов. Данные о политропизме TTV опровергают возможность его отнесения исключительно к вирусам гепатита. Высокая распространенность вируса ТТ в человеческой популяции указывает на его персистенцию в организме в составе вирома и свидетельствует в пользу его непатогенности. Предлагается использовать уровень ДНК TTV в крови пациентов перед трансплантацией органов в качестве эндогенного маркера иммунного статуса организма. Выводы: Высокая распространенность вируса ТТ в человеческой популяции указывает на его персистенцию в организме в составе вирома. Редкое выявление повреждающего действия TTV на клетки печени и эпителио циты желчных протоков может косвенно свидетельствовать о его условно-патогенных свойствах. Ключевые слова: torque teno virus, виром, гепатит, вирусы гепатита, иммуносупрессия, трансплантация Конфликт интересов: Авторы заявляют об отсутствии конфликтов интересов.

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The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Cited by 26 publications

References 28 publications

Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation

Torque Teno Virus as a Potential Biomarker for Complications and Survival After Allogeneic Hematopoietic Stem Cell Transplantation

Cell-free DNA Profiling Informs Major Complications of Hematopoietic Cell Transplantation

Current Views of Torque Teno Virus (TTV) in Liver Diseases

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