Anellovirus loads are associated with outcomes in pediatric lung transplantation

Joshua A. Blatter; Stuart C. Sweet; Carol Conrad; Lara A. Danziger-Isakov; Albert Faro; Samuel B. Goldfarb; Don Hayes; Ernestina Melicoff; Marc Schecter; Gregory Storch; Gary A. Visner; Nikki M. Williams; David Wang

doi:10.1111/petr.13069

Anellovirus loads are associated with outcomes in pediatric lung transplantation

Joshua A. Blatter, Stuart C. Sweet, Carol Conrad, Lara A. Danziger-Isakov, Albert Faro, Samuel B. Goldfarb, Don Hayes, Ernestina Melicoff, Marc Schecter, Gregory Storch, Gary A. Visner, Nikki M. Williams, David Wang

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as “composite” (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P =.013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P =.047) and the composite outcome (P =.017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

Original language	English (US)
Article number	e13069
Journal	Pediatric transplantation
Volume	22
Issue number	1
DOIs	https://doi.org/10.1111/petr.13069
State	Published - Feb 2018
Externally published	Yes

Bibliographical note

Funding Information:
This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection.

Funding Information:
This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection.

Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

acute rejection
biomarkers
chronic
immunosuppression
pediatric lung transplantation
rejection

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10.1111/petr.13069

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title = "Anellovirus loads are associated with outcomes in pediatric lung transplantation",

abstract = "Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as “composite” (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P =.013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P =.047) and the composite outcome (P =.017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.",

keywords = "acute rejection, biomarkers, chronic, immunosuppression, pediatric lung transplantation, rejection",

author = "Blatter, {Joshua A.} and Sweet, {Stuart C.} and Carol Conrad and Danziger-Isakov, {Lara A.} and Albert Faro and Goldfarb, {Samuel B.} and Don Hayes and Ernestina Melicoff and Marc Schecter and Gregory Storch and Visner, {Gary A.} and Williams, {Nikki M.} and David Wang",

note = "Funding Information: This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection. Funding Information: This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection. Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2018",

month = feb,

doi = "10.1111/petr.13069",

language = "English (US)",

volume = "22",

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T1 - Anellovirus loads are associated with outcomes in pediatric lung transplantation

AU - Blatter, Joshua A.

AU - Sweet, Stuart C.

AU - Conrad, Carol

AU - Danziger-Isakov, Lara A.

AU - Faro, Albert

AU - Goldfarb, Samuel B.

AU - Hayes, Don

AU - Melicoff, Ernestina

AU - Schecter, Marc

AU - Storch, Gregory

AU - Visner, Gary A.

AU - Williams, Nikki M.

AU - Wang, David

N1 - Funding Information: This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection. Funding Information: This research was performed as a project of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases. JAB and DW were supported by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. JAB was supported by K12 H120002. JAB and SCS were supported by U01 AI077810. We would like to thank the patients who contributed samples to this collection. Publisher Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

PY - 2018/2

Y1 - 2018/2

N2 - Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as “composite” (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P =.013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P =.047) and the composite outcome (P =.017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

AB - Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as “composite” (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P =.013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P =.047) and the composite outcome (P =.017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

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KW - biomarkers

KW - chronic

KW - immunosuppression

KW - pediatric lung transplantation

KW - rejection

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ER -

Anellovirus loads are associated with outcomes in pediatric lung transplantation

Abstract

Bibliographical note

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