Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation

Albert, Eliseo; Solano, Carlos; Giménez, Estela; Focosi, Daniele; Pérez, Ariadna; Macera, Lisa; Piñana, José Luís; Mateo, Eva M.; Boluda, Juan Carlos Hernández; Maggi, Fabrizio; Navarro, David

doi:10.1007/s00430-019-00586-w

Cited by 17 publications

(38 citation statements)

References 17 publications

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“…Chronic HBV and HEV infections were also confirmed by mNGS in two patients. Anelloviridae (TTV, TTMV, and TTMDV) were the most prevalent in this study, concordant with the high TTV viremia rate identified among allo-HSCT recipients [28][29][30][31]. The high TTV, TTMV, and TTMDV codetection rate has been previously described [30].…”

Section: Discussionsupporting

confidence: 89%

Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease

et al. 2021

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Background Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses. Results Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; Anelloviridae (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1). Conclusions Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection.

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Section: Discussionsupporting

confidence: 89%

Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease

et al. 2021

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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: 84%

“…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%

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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“…In allo-HSCT recipients, the peak of TTV viral load occurs approximately at 3–6 months post-transplant before returning to the value observed prior to transplantation [ 9 , 26 ]. In the present study, we observed that at 6 months post-transplant during the immune reconstitution period, some patients are still unable to regulate the TTV replication, leading to high blood viral load, despite a sufficient number of T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…The use of an immune functional assay (IFA) such as the assessment of post-stimulation T-cell proliferation capacity could fill this need but its implementation in clinical practice remains difficult. TTV could be interesting as a biomarker to estimate immune function and finally to predict infectious and/or clinical events related to the immune system [ 5 , 9 , 22 , 26 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients

Mouton

Conrad

Bal

et al. 2020

Viruses

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Torque teno virus (TTV) has been proposed as a surrogate biomarker of T-cell function in allogeneic–haematopoietic–stem-cell transplantation (allo-HSCT). Conflicting data exists regarding the value of TTV to assess the degree of immunosuppression. The aim of the present study was to investigate the correlation between TTV viral load and immune function. Using samples from a prospective cohort composed of healthy-volunteers (HV) and allo-HSCT recipients at 6 months post-transplantation, we assessed the correlation between TTV viraemia and immune cell counts or T-cell proliferation capacity post-phytohaemagglutinin stimulation. TTV viraemia was detected in 68% of HV (n = 80) and 100% of allo-HSCT recipients (n = 41; p < 0.001); it was significantly higher in allo-HSCT recipients (3.9 vs. 2.1 Log copies/mL, p < 0.001). There was no correlation between T-cell function and CD3+T-cell count (rho: 0.002) suggesting that T-cell count can normalise without full functional recovery. Furthermore, no significant correlation was observed between TTV viraemia and absolute total/subset lymphocyte counts (rho: <0.13). The highest correlation was observed between TTV viral load and T-cell proliferation capacity (rho: −0.39). We therefore report an inverse correlation between T-cell function and TTV viraemia that is independent of T-cell count. Monitoring of TTV viraemia could be a fast suitable option to objectively assess the competence of immune function in at-risk populations.

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Kinetics of Alphatorquevirus plasma DNAemia at late times after allogeneic hematopoietic stem cell transplantation

Cited by 17 publications

References 17 publications

Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease

Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease

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

Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients

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