Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry

<i>Background and Objectives</i>: There is no biomarker to predict lithium response. This study used <i>CellPrint</i>™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4<sup>+</sup> lymphocytes before and...

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Main Authors: Keming Gao, Nicholas M. Kaye, Marzieh Ayati, Mehmet Koyuturk, Joseph R. Calabrese, Eric Christian, Hillard M. Lazarus, David Kaplan
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1648-9144/59/1/120
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author Keming Gao
Nicholas M. Kaye
Marzieh Ayati
Mehmet Koyuturk
Joseph R. Calabrese
Eric Christian
Hillard M. Lazarus
David Kaplan
author_facet Keming Gao
Nicholas M. Kaye
Marzieh Ayati
Mehmet Koyuturk
Joseph R. Calabrese
Eric Christian
Hillard M. Lazarus
David Kaplan
author_sort Keming Gao
collection DOAJ
description <i>Background and Objectives</i>: There is no biomarker to predict lithium response. This study used <i>CellPrint</i>™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4<sup>+</sup> lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). <i>Materials and Methods</i>: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4<sup>+</sup> lymphocytes and monocytes were analyzed with <i>CellPrint</i>™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. <i>Results</i>: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. <i>Conclusions</i>: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.
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spelling doaj.art-4f9ca3a8b9a948f2b20a4356544c6ded2023-11-30T23:24:38ZengMDPI AGMedicina1010-660X1648-91442023-01-0159112010.3390/medicina59010120Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow CytometryKeming Gao0Nicholas M. Kaye1Marzieh Ayati2Mehmet Koyuturk3Joseph R. Calabrese4Eric Christian5Hillard M. Lazarus6David Kaplan7Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USACellPrint Biotechnology, Cleveland, OH 44106, USADepartment of Computer Science, University of Texas Rio Grande Valley, Edinburg, TX 78539, USADepartment of Computer and Data Sciences, Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USACellPrint Biotechnology, Cleveland, OH 44106, USACase Western Reserve University School of Medicine, Cleveland, OH 44106, USACellPrint Biotechnology, Cleveland, OH 44106, USA<i>Background and Objectives</i>: There is no biomarker to predict lithium response. This study used <i>CellPrint</i>™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4<sup>+</sup> lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). <i>Materials and Methods</i>: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4<sup>+</sup> lymphocytes and monocytes were analyzed with <i>CellPrint</i>™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. <i>Results</i>: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. <i>Conclusions</i>: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted.https://www.mdpi.com/1648-9144/59/1/120lithium treatmentbipolar disordermonocytes and CD4<sup>+</sup> lymphocytesbiomarkersintracellular proteins
spellingShingle Keming Gao
Nicholas M. Kaye
Marzieh Ayati
Mehmet Koyuturk
Joseph R. Calabrese
Eric Christian
Hillard M. Lazarus
David Kaplan
Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
Medicina
lithium treatment
bipolar disorder
monocytes and CD4<sup>+</sup> lymphocytes
biomarkers
intracellular proteins
title Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
title_full Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
title_fullStr Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
title_full_unstemmed Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
title_short Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry
title_sort divergent directionality of immune cell specific protein expression between bipolar lithium responders and non responders revealed by enhanced flow cytometry
topic lithium treatment
bipolar disorder
monocytes and CD4<sup>+</sup> lymphocytes
biomarkers
intracellular proteins
url https://www.mdpi.com/1648-9144/59/1/120
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