title: Screening for novel central nervous system biomarkers in veterans with Gulf War Illness.
abstract: Gulf War illness (GWI) is primarily diagnosed by symptom report; objective biomarkers are needed that distinguish those with GWI. Prior chemical exposures during deployment have been associated in epidemiologic studies with altered central nervous system functioning in veterans with GWI. Previous studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins in patients with brain injury and autoantibodies have been identified as candidate objective markers that may distinguish GWI. Here, we screened the serum of 20 veterans with GWI and 10 non-veteran symptomatic (low back pain) controls for the presence of such autoantibodies using Western blot analysis against the following proteins: neurofilament triplet proteins (NFP), tubulin, microtubule associated tau proteins (Tau), microtubule associated protein-2 (MAP-2), myelin basic protein (MBP), myelin associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII) and glial S-100B protein. Serum reactivity was measured as arbitrary chemiluminescence units. As a group, veterans with GWI had statistically significantly higher levels of autoantibody reactivity in all proteins examined except S-100B. Fold increase of the cases relative to controls in descending order were: CaMKII 9.27, GFAP 6.60, Tau 4.83, Tubulin 4.41, MAG 3.60, MBP 2.50, NFP 2.45, MAP-2 2.30, S-100B 1.03. These results confirm the continuing presence of neuronal injury/gliosis in these veterans and are in agreement with the recent reports indicating that 25years after the war, the health of veterans with GWI is not improving and may be getting worse. Such serum autoantibodies may prove useful as biomarkers of GWI, upon validation of the findings using larger cohorts.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, United States. Electronic address: donia@duke.edu.
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Abou-Donia
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Conboy
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
authors.affiliation: Department of Global Health and Social Development, Harvard Medical School, United States; Department of Environmental Health, Boston University School of Public Health, Boston, MA, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Jacobson
authors.affiliation: Department of Microbiology, Zagazig University, Zagazig, Egypt.
authors.forename: Eman M
authors.initials: EM
authors.lastname: Elmasry
authors.affiliation: Department of Math and Computer Science, Menoufia University, Shebin ElKom, Egypt.
authors.forename: Passent
authors.initials: P
authors.lastname: Elkafrawy
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University Medical Center, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Neely
authors.affiliation: Biomedical Engineering Department, Duke University, United States.
authors.forename: Cameron R 'Dale'
authors.initials: CR'
authors.lastname: Bass
authors.affiliation: Biomedical Engineering Department, Duke University, United States.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D018923:Persian Gulf Syndrome / Q000097:blood*; D014728:Veterans
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D009419:Nerve Tissue Proteins
keywords: Autoantibodies; Brain injury; Cytoskeletal proteins; Gulf War Illness; Serum biomarkers