Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease

Siddhee A. Sahasrabudhe; Marcia R. Terluk; Kyle D. Rudser; James C. Cloyd; Reena V. Kartha

doi:10.3390/ijms23169189

Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease

Siddhee A. Sahasrabudhe, Marcia R. Terluk, Kyle D. Rudser, James C. Cloyd, Reena V. Kartha

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

3 Scopus citations

Abstract

The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.

Original language	English (US)
Article number	9189
Journal	International journal of molecular sciences
Volume	23
Issue number	16
DOIs	https://doi.org/10.3390/ijms23169189
State	Published - Aug 2022

Bibliographical note

Funding Information:
Financial support was provided by Sanofi, Pfizer Inc., and the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), and the National Center for Advancing Translational Sciences (NCATS). This consortium is funded through a collaboration between NCATS, NINDS, and NIDDK. Research reported in this publication was also supported by the NCATS Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
S.A.S., M.R.T., K.D.R. report no financial disclosures and conflict of interest in reference to this work. R.V.K. and J.C.C. have received investigator-initiated funds from Pfizer Inc., Sanofi, and the NIH.

Publisher Copyright:
© 2022 by the authors.

Keywords

Bland–Altman
Gaucher disease
biomarkers
inflammation
oxidative stress
therapy
variability

Publisher link

10.3390/ijms23169189

Find It

Find It at U of M Libraries

Cite this

@article{9534bb7175a54122a3b0ffff2aec1c09,

title = "Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease",

abstract = "The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-na{\"i}ve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.",

keywords = "Bland–Altman, Gaucher disease, biomarkers, inflammation, oxidative stress, therapy, variability",

author = "Sahasrabudhe, {Siddhee A.} and Terluk, {Marcia R.} and Rudser, {Kyle D.} and Cloyd, {James C.} and Kartha, {Reena V.}",

note = "Funding Information: Financial support was provided by Sanofi, Pfizer Inc., and the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), and the National Center for Advancing Translational Sciences (NCATS). This consortium is funded through a collaboration between NCATS, NINDS, and NIDDK. Research reported in this publication was also supported by the NCATS Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: S.A.S., M.R.T., K.D.R. report no financial disclosures and conflict of interest in reference to this work. R.V.K. and J.C.C. have received investigator-initiated funds from Pfizer Inc., Sanofi, and the NIH. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = aug,

doi = "10.3390/ijms23169189",

language = "English (US)",

volume = "23",

journal = "International journal of molecular sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "16",

}

TY - JOUR

T1 - Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease

AU - Sahasrabudhe, Siddhee A.

AU - Terluk, Marcia R.

AU - Rudser, Kyle D.

AU - Cloyd, James C.

AU - Kartha, Reena V.

N1 - Funding Information: Financial support was provided by Sanofi, Pfizer Inc., and the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), and the National Center for Advancing Translational Sciences (NCATS). This consortium is funded through a collaboration between NCATS, NINDS, and NIDDK. Research reported in this publication was also supported by the NCATS Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: S.A.S., M.R.T., K.D.R. report no financial disclosures and conflict of interest in reference to this work. R.V.K. and J.C.C. have received investigator-initiated funds from Pfizer Inc., Sanofi, and the NIH. Publisher Copyright: © 2022 by the authors.

PY - 2022/8

Y1 - 2022/8

N2 - The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.

AB - The lack of reliable biomarkers is a significant challenge impeding progress in orphan drug development. For appropriate interpretation of intervention-based results or for evaluating candidate biomarkers, other things being equal, lower variability in biomarker measurement would be helpful. However, variability in rare disease biomarkers is often poorly understood. Type 1 Gaucher disease (GD1) is one such rare lysosomal storage disorder. Oxidative stress and inflammation have been linked to the pathophysiology of GD1 and validated measures of these processes can provide predictive value for treatment success or disease progression. This study was undertaken to investigate and compare the extent of longitudinal biological variation over a three-month period for various blood-based oxidative stress and inflammation markers in participants with GD1 on stable standard-of-care therapy (N = 13), treatment-naïve participants with GD1 (N = 5), and in age- and gender-matched healthy volunteers (N = 18). We utilized Bland–Altman plots for visual comparison of the biological variability among the three measurements. We also report group-wise means and the percentage of coefficient of variation (%CV) for 15 biomarkers. Qualitatively, we show specific markers (IL-1Ra, IL-8, and MIP-1b) to be consistently altered in GD1, irrespective of therapy status, highlighting the need for adjunctive therapies that can target and modulate these biomarkers. This information can help guide the selection of candidate biomarkers for future intervention-based studies in GD1 patients.

KW - Bland–Altman

KW - Gaucher disease

KW - biomarkers

KW - inflammation

KW - oxidative stress

KW - therapy

KW - variability

UR - http://www.scopus.com/inward/record.url?scp=85136675750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85136675750&partnerID=8YFLogxK

U2 - 10.3390/ijms23169189

DO - 10.3390/ijms23169189

M3 - Article

C2 - 36012454

AN - SCOPUS:85136675750

SN - 1661-6596

VL - 23

JO - International journal of molecular sciences

JF - International journal of molecular sciences

IS - 16

M1 - 9189

ER -

Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this