TY - JOUR
T1 - Investigating the Eye as a Biomarker of Gulf War Illness
T2 - Sphingolipid and Eicosanoid Composition in Tears and Plasma
AU - Paule Jimenez, Laura Beatriz
AU - Prislovsky, Amanda
AU - Parchejo, Loralei Ann
AU - Cabrera, Kimberly
AU - Nafziger, Andrew J.
AU - Stephenson, Daniel J.
AU - Chalfant, Charles E.
AU - Aenlle, Kristina
AU - Klimas, Nancy
AU - Tang, Fei
AU - Mandal, Nawajes
AU - Galor, Anat
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/12
Y1 - 2025/12
N2 - Gulf War Illness (GWI) is a chronic multi-symptom condition affecting veterans of the 1990–1991 Gulf War, with ocular discomfort increasingly recognized among its manifestations. This pilot study evaluated whether lipid alterations in tears and plasma could serve as potential biomarkers of GWI. Participants included Gulf War-era veterans seen in the Miami Veterans Affairs Hospital eye clinic from 2018–2022. Cases met GWI criteria, while controls were non-deployed, age- and gender-matched veterans without GWI. Participants completed systemic and ocular symptom questionnaires, and lipidomic profiling of tears and plasma quantified sphingolipids and eicosanoids. Compared to controls (n = 21), GWI cases (n = 19) reported greater ocular symptom burden, while ocular signs were similar between groups. Lipidomic analyses revealed increased tear eicosanoids ((±)14(15)-EET and (±)8(9)-EET), elevated plasma sphingomyelins (SM C16:0 DH, SM C20:0, SM C22:0), and reduced plasma monohexosylceramide (MHC C16:0) and sphingomyelin (SM C14:0) in cases. Logistic regression and random forest models identified plasma SM C16:0 DH and SM C20:0 as top predictors distinguishing GWI cases from controls, with an area under the receiver operating characteristic curve (AUC) of 0.89. These findings suggest lipid dysregulation in ocular and systemic compartments and support further investigation of tears as a minimally invasive source for biomarker discovery.
AB - Gulf War Illness (GWI) is a chronic multi-symptom condition affecting veterans of the 1990–1991 Gulf War, with ocular discomfort increasingly recognized among its manifestations. This pilot study evaluated whether lipid alterations in tears and plasma could serve as potential biomarkers of GWI. Participants included Gulf War-era veterans seen in the Miami Veterans Affairs Hospital eye clinic from 2018–2022. Cases met GWI criteria, while controls were non-deployed, age- and gender-matched veterans without GWI. Participants completed systemic and ocular symptom questionnaires, and lipidomic profiling of tears and plasma quantified sphingolipids and eicosanoids. Compared to controls (n = 21), GWI cases (n = 19) reported greater ocular symptom burden, while ocular signs were similar between groups. Lipidomic analyses revealed increased tear eicosanoids ((±)14(15)-EET and (±)8(9)-EET), elevated plasma sphingomyelins (SM C16:0 DH, SM C20:0, SM C22:0), and reduced plasma monohexosylceramide (MHC C16:0) and sphingomyelin (SM C14:0) in cases. Logistic regression and random forest models identified plasma SM C16:0 DH and SM C20:0 as top predictors distinguishing GWI cases from controls, with an area under the receiver operating characteristic curve (AUC) of 0.89. These findings suggest lipid dysregulation in ocular and systemic compartments and support further investigation of tears as a minimally invasive source for biomarker discovery.
KW - biomarkers
KW - eicosanoids
KW - gulf war illness
KW - inflammation
KW - lipidomics
KW - ocular surface
KW - plasma
KW - sphingolipids
KW - tears
UR - https://www.scopus.com/pages/publications/105025667431
UR - https://www.scopus.com/pages/publications/105025667431#tab=citedBy
U2 - 10.3390/biom15121716
DO - 10.3390/biom15121716
M3 - Article
C2 - 41463371
AN - SCOPUS:105025667431
SN - 2218-273X
VL - 15
JO - Biomolecules
JF - Biomolecules
IS - 12
M1 - 1716
ER -