Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against...

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Main Authors: Mohamed B. Abou-Donia, Elizabeth S. Lapadula, Maxine H. Krengel, Emily Quinn, Jessica LeClair, Joseph Massaro, Lisa A. Conboy, Efi Kokkotou, Maria Abreu, Nancy G. Klimas, Daniel D. Nguyen, Kimberly Sullivan
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/10/9/610
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author Mohamed B. Abou-Donia
Elizabeth S. Lapadula
Maxine H. Krengel
Emily Quinn
Jessica LeClair
Joseph Massaro
Lisa A. Conboy
Efi Kokkotou
Maria Abreu
Nancy G. Klimas
Daniel D. Nguyen
Kimberly Sullivan
author_facet Mohamed B. Abou-Donia
Elizabeth S. Lapadula
Maxine H. Krengel
Emily Quinn
Jessica LeClair
Joseph Massaro
Lisa A. Conboy
Efi Kokkotou
Maria Abreu
Nancy G. Klimas
Daniel D. Nguyen
Kimberly Sullivan
author_sort Mohamed B. Abou-Donia
collection DOAJ
description For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (<i>n</i> = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and <i>n</i> = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.
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spelling doaj.art-17170adb04ec41aba7d49a96792a8e712023-11-20T12:40:47ZengMDPI AGBrain Sciences2076-34252020-09-0110961010.3390/brainsci10090610Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic ControlsMohamed B. Abou-Donia0Elizabeth S. Lapadula1Maxine H. Krengel2Emily Quinn3Jessica LeClair4Joseph Massaro5Lisa A. Conboy6Efi Kokkotou7Maria Abreu8Nancy G. Klimas9Daniel D. Nguyen10Kimberly Sullivan11Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USADepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USADepartment of Neurology, Boston University School of Medicine, Boston, MA 02118, USADepartments of Biostatistics and Environmental Health, Boston University School of Public Health, Boston, MA 02118, USADepartments of Biostatistics and Environmental Health, Boston University School of Public Health, Boston, MA 02118, USADepartments of Biostatistics and Environmental Health, Boston University School of Public Health, Boston, MA 02118, USADepartment of Medicine, Harvard Medical School, Boston, MA 02115, USADepartment of Medicine, Harvard Medical School, Boston, MA 02115, USADr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuroimmune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USADr. Kiran C. Patel College of Osteopathic Medicine, Institute for Neuroimmune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USADepartments of Biostatistics and Environmental Health, Boston University School of Public Health, Boston, MA 02118, USADepartments of Biostatistics and Environmental Health, Boston University School of Public Health, Boston, MA 02118, USAFor the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (<i>n</i> = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and <i>n</i> = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups.https://www.mdpi.com/2076-3425/10/9/610etiologyGulf War IllnessCNS autoantibodiesmyalgic encephalomyelitis/chronic fatigue syndromeirritable bowel syndrome
spellingShingle Mohamed B. Abou-Donia
Elizabeth S. Lapadula
Maxine H. Krengel
Emily Quinn
Jessica LeClair
Joseph Massaro
Lisa A. Conboy
Efi Kokkotou
Maria Abreu
Nancy G. Klimas
Daniel D. Nguyen
Kimberly Sullivan
Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
Brain Sciences
etiology
Gulf War Illness
CNS autoantibodies
myalgic encephalomyelitis/chronic fatigue syndrome
irritable bowel syndrome
title Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
title_full Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
title_fullStr Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
title_full_unstemmed Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
title_short Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
title_sort using plasma autoantibodies of central nervous system proteins to distinguish veterans with gulf war illness from healthy and symptomatic controls
topic etiology
Gulf War Illness
CNS autoantibodies
myalgic encephalomyelitis/chronic fatigue syndrome
irritable bowel syndrome
url https://www.mdpi.com/2076-3425/10/9/610
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