Abstract
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 (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 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.
Highlights
The 1991 Gulf War (GW) only had less than two months of air strikes and less than a week of ground combat, approximately one-third of the 697,000 U.S veterans developed a combination of health symptom complaints, including debilitating fatigue, chronic headache and body pain, memory and concentration difficulties, gastrointestinal problems, and skin abnormalities, known as Gulf War illness (GWI) [1,2,3]
We reported on a pilot study of serum biomarkers, which found seven out of eight markers significantly differed in veterans with GWI versus symptomatic controls with lower back pain, suggesting new potential blood markers for GWI [12]
Chronic symptoms reported by veterans with GWI have included headache, memory memory and and attention attention decrements, decrements, debilitating debilitating fatigue, fatigue,chronic chronic pain, pain, and and gastrointestinal gastrointestinal headache, problems
Summary
The 1991 Gulf War (GW) only had less than two months of air strikes and less than a week of ground combat, approximately one-third of the 697,000 U.S veterans developed a combination of health symptom complaints, including debilitating fatigue, chronic headache and body pain, memory and concentration difficulties, gastrointestinal problems, and skin abnormalities, known as Gulf War illness (GWI) [1,2,3]. Some GW veterans had increased rates of two other distinct conditions, Irritable Bowel Syndrome (IBS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which have overlapping symptoms with GWI [4,5]. Given these overlapping symptoms with other chronic conditions, it has been difficult to confirm the presence or absence of GWI or to differentiate between these disorders [6,7,8]. We reported on a pilot study of serum biomarkers, which found seven out of eight markers significantly differed in veterans with GWI versus symptomatic controls with lower back pain, suggesting new potential blood markers for GWI [12]. The current study expanded on these prior findings by adding newly developed cutting-edge blood plasma autoantibodies in GW veteran and civilian cohorts, including those with IBS and ME/CFS, to identify whether veterans with
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