4.1 Article

Screening for novel central nervous system biomarkers in veterans with Gulf War Illness

Journal

NEUROTOXICOLOGY AND TERATOLOGY
Volume 61, Issue -, Pages 36-46

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2017.03.002

Keywords

Gulf War Illness; Brain injury; Autoantibodies; Cytoskeletal proteins; Serum biomarkers

Funding

  1. DOD [W81XWH-15-1-0641, W81XWH-15-1-0640, W81XWH-09-0064]
  2. National Center for Complementary and Integrative Health, the National Institutes of Health [K01AT004916]

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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), caldum-calmodulin kinase II (CaMKII) and glial 5-100B 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 5-100B. Fold increase of the cases relative to controls in descending order were: CaMKII 927, 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 25 years 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. (C) 2017 Elsevier Inc. All rights reserved.

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