Cargando…

Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development

Background: Clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. This report provides comprehensive clinical and immunological ref...

Descripción completa

Detalles Bibliográficos
Autores principales: Merino, Kristen M., Slisarenko, Nadia, Taylor, Joshua M., Falkenstein, Kathrine P., Gilbert, Margaret H., Bohm, Rudolf P., Blanchard, James L., Ardeshir, Amir, Didier, Elizabeth S., Kim, Woong-Ki, Kuroda, Marcelo J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378395/
https://www.ncbi.nlm.nih.gov/pubmed/32766187
http://dx.doi.org/10.3389/fped.2020.00388
_version_ 1783562410581295104
author Merino, Kristen M.
Slisarenko, Nadia
Taylor, Joshua M.
Falkenstein, Kathrine P.
Gilbert, Margaret H.
Bohm, Rudolf P.
Blanchard, James L.
Ardeshir, Amir
Didier, Elizabeth S.
Kim, Woong-Ki
Kuroda, Marcelo J.
author_facet Merino, Kristen M.
Slisarenko, Nadia
Taylor, Joshua M.
Falkenstein, Kathrine P.
Gilbert, Margaret H.
Bohm, Rudolf P.
Blanchard, James L.
Ardeshir, Amir
Didier, Elizabeth S.
Kim, Woong-Ki
Kuroda, Marcelo J.
author_sort Merino, Kristen M.
collection PubMed
description Background: Clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. This report provides comprehensive clinical and immunological reference ranges for pediatric rhesus macaques over the first year of life. Methods: We collected and analyzed blood samples from 151 healthy rhesus macaques, aged 0–55 weeks, and compared mother-reared infants to two categories of nursery-reared infants; those on an active research protocol and those under derivation for the expanded specific-pathogen-free breeding colony. Hematology was performed on EDTA-anticoagulated blood using a Sysmex XT2000i, and serum clinical chemistry was performed using the Beckman AU480 chemistry analyzer. Immunophenotyping of whole blood was performed with immunofluorescence staining and subsequent flow cytometric analysis on a BD LSRFortessa. Plasma cytokine analysis was performed using a Millipore multiplex Luminex assay. Results: For hematological and chemistry measurements, pediatric reference ranges deviate largely from adults. Comparison of mother-reared and nursery-reared animals revealed that large differences depend on rearing conditions and diet. Significant differences found between two nursery-reared cohorts (research and colony animals) indicate large influences of experimental factors and anesthetic events on these parameters. Immune cells and cytokine responses presented with distinct patterns for infants depending on age, birth location, and rearing conditions. Conclusions: Our results illustrate how the immune system changed over time and that there was variability among pediatric age groups. Reference ranges of results reported here will support interpretations for how infection and treatment may skew common immune correlates used for assessment of pathology or protection in research studies as well as help veterinarians in the clinical care of infant non-human primates. We highlighted the importance of using age-specific reference comparisons for pediatric studies and reiterated the utility of rhesus macaques as a model for human studies. Given the rapid transformation that occurs in multiple tissue compartments after birth and cumulative exposures to antigens as individuals grow, a better understanding of immunological development and how this relates to timing of infection or vaccination will support optimal experimental designs for developing vaccines and treatment interventions.
format Online
Article
Text
id pubmed-7378395
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-73783952020-08-05 Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development Merino, Kristen M. Slisarenko, Nadia Taylor, Joshua M. Falkenstein, Kathrine P. Gilbert, Margaret H. Bohm, Rudolf P. Blanchard, James L. Ardeshir, Amir Didier, Elizabeth S. Kim, Woong-Ki Kuroda, Marcelo J. Front Pediatr Pediatrics Background: Clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. This report provides comprehensive clinical and immunological reference ranges for pediatric rhesus macaques over the first year of life. Methods: We collected and analyzed blood samples from 151 healthy rhesus macaques, aged 0–55 weeks, and compared mother-reared infants to two categories of nursery-reared infants; those on an active research protocol and those under derivation for the expanded specific-pathogen-free breeding colony. Hematology was performed on EDTA-anticoagulated blood using a Sysmex XT2000i, and serum clinical chemistry was performed using the Beckman AU480 chemistry analyzer. Immunophenotyping of whole blood was performed with immunofluorescence staining and subsequent flow cytometric analysis on a BD LSRFortessa. Plasma cytokine analysis was performed using a Millipore multiplex Luminex assay. Results: For hematological and chemistry measurements, pediatric reference ranges deviate largely from adults. Comparison of mother-reared and nursery-reared animals revealed that large differences depend on rearing conditions and diet. Significant differences found between two nursery-reared cohorts (research and colony animals) indicate large influences of experimental factors and anesthetic events on these parameters. Immune cells and cytokine responses presented with distinct patterns for infants depending on age, birth location, and rearing conditions. Conclusions: Our results illustrate how the immune system changed over time and that there was variability among pediatric age groups. Reference ranges of results reported here will support interpretations for how infection and treatment may skew common immune correlates used for assessment of pathology or protection in research studies as well as help veterinarians in the clinical care of infant non-human primates. We highlighted the importance of using age-specific reference comparisons for pediatric studies and reiterated the utility of rhesus macaques as a model for human studies. Given the rapid transformation that occurs in multiple tissue compartments after birth and cumulative exposures to antigens as individuals grow, a better understanding of immunological development and how this relates to timing of infection or vaccination will support optimal experimental designs for developing vaccines and treatment interventions. Frontiers Media S.A. 2020-07-16 /pmc/articles/PMC7378395/ /pubmed/32766187 http://dx.doi.org/10.3389/fped.2020.00388 Text en Copyright © 2020 Merino, Slisarenko, Taylor, Falkenstein, Gilbert, Bohm, Blanchard, Ardeshir, Didier, Kim and Kuroda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Merino, Kristen M.
Slisarenko, Nadia
Taylor, Joshua M.
Falkenstein, Kathrine P.
Gilbert, Margaret H.
Bohm, Rudolf P.
Blanchard, James L.
Ardeshir, Amir
Didier, Elizabeth S.
Kim, Woong-Ki
Kuroda, Marcelo J.
Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title_full Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title_fullStr Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title_full_unstemmed Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title_short Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development
title_sort clinical and immunological metrics during pediatric rhesus macaque development
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378395/
https://www.ncbi.nlm.nih.gov/pubmed/32766187
http://dx.doi.org/10.3389/fped.2020.00388
work_keys_str_mv AT merinokristenm clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT slisarenkonadia clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT taylorjoshuam clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT falkensteinkathrinep clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT gilbertmargareth clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT bohmrudolfp clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT blanchardjamesl clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT ardeshiramir clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT didierelizabeths clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT kimwoongki clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment
AT kurodamarceloj clinicalandimmunologicalmetricsduringpediatricrhesusmacaquedevelopment