Abstract
Background and Objectives To increase the validity of biomarker measures in multiple sclerosis (MS), factors affecting their concentration need to be identified. Here, we test whether the volume of distribution approximated by the patients' estimated blood volume (BV) and body mass index (BMI) affect the serum concentrations of glial fibrillary acidic protein (GFAP). As a control, we also determine the relationship between BV/BMI and GFAP concentrations in CSF. To confirm earlier findings, we test the same hypotheses for neurofilament light chain (NfL).
Methods NfL and GFAP concentrations were measured in serum and CSF (sNFL/sGFAP and cNFL/cGFAP) in 157 patients (n = 106 with MS phenotype and n = 51 with other neurologic/somatoform diseases). Using multivariate linear regressions, BV was tested in the MS cohort as a predictor for each of the biomarkers while controlling for age, sex, MS phenotype, Expanded Disability Status Scale score, gadolinium-enhancing lesions, and acute relapse. In addition, overweight/obese patients (BMI ≥25 kg/m2) were compared with patients with BMI <25 kg/m2 using the general linear model. The analyses were repeated including the neurologic/somatoform controls.
Results In the MS cohort, BV predicted sGFAP (ß = −0.301, p = 0.014). Overweight/obese patients with MS had lower sGFAP concentrations compared with patients with MS and BMI <25 kg/m2 (F = 4.732, p = 0.032). Repeating the analysis after adding patients with other neurologic/somatoform diseases did not change these findings (ß = −0.276, p = 0.009; F = 7.631, p = 0.006). Although sNfL was inversely correlated with BV (r = −0.275, p = 0.006) and body weight (r = −0.258, p = 0.010), those results did not remain significant after adjusting for covariates. BV and BMI were not associated with cGFAP or cNfL concentrations.
Discussion These findings support the notion that the volume of distribution of sGFAP approximated by BV and BMI is a relevant variable and should therefore be controlled for when measuring sGFAP in MS, while this might not be necessary when measuring cGFAP concentrations.
Glossary
- AN=
- anorexia nervosa;
- BMI=
- body mass index;
- BV=
- blood volume;
- cGFAP=
- glial fibrillary acidic protein in CSF;
- CIS=
- clinically isolated syndrome;
- cNfL=
- neurofilament light chain measured in CSF;
- DMT=
- disease-modifying therapy;
- EDSS=
- Expanded Disability Status Scale;
- FDR=
- false-discovery rate;
- GFAP=
- glial fibrillary acidic protein;
- GLM=
- general linear model;
- IQR=
- interquartile range;
- MS=
- multiple sclerosis;
- PPMS=
- primary progressive multiple sclerosis;
- RIS=
- radiologically isolated syndrome;
- RRMS=
- relapsing-remitting multiple sclerosis;
- sGFAP=
- glial fibrillary acidic protein in serum;
- sNfL=
- neurofilament light chain measured in serum
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by University Hospital Frankfurt.
Submitted and externally peer reviewed. The handling editor was Scott S. Zamvil, MD, PhD, FAAN.
- Received April 14, 2022.
- Accepted in final form August 30, 2022.
- Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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