Adaptive Immune Responses Associated with the Central Nervous System Pathology of Gulf War Illness

1. White, RF, Steele, L, O’Callaghan, JP, et al. Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: effects of toxicant exposures during deployment. Cortex. 2016;74:449-475.
Google Scholar | Crossref | Medline2. Binns, J, Barlow, C, Bloom, FE, et al. Research Advisory Committee on Gulf War Veterans’ Illnesses: Gulf War Illness and the Health of Gulf War Veterans: Scientific Findings and Recommendations. U.S. Government Printing Office; 2008.
Google Scholar3. Unwin, C, Blatchley, N, Coker, W, et al. Health of UK servicemen who served in Persian Gulf War. Lancet. 1999;353(9148):169-178.
Google Scholar | Crossref | Medline4. Hotopf, M, David, A, Hull, L, Ismail, K, Unwin, C, Wessely, S. Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study. BMJ. 2000;320(7246):1363-1367.
Google Scholar | Crossref | Medline5. Mawson, AR, Croft, AM. Gulf War illness: unifying hypothesis for a continuing health problem. Int J Environ Res Public Health. 2019;16(1):111.
Google Scholar | Crossref6. Rook, GA, Zumla, A. Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile? Lancet. 1997;349(9068):1831-1833.
Google Scholar | Crossref | Medline7. Hotopf, M. Reanalysis of Gulf war vaccination data does not contradict findings. BMJ. 2000;321(7263):761-762.
Google Scholar | Crossref | Medline8. Cherry, N, Creed, F, Silman, A, et al. Health and exposures of United Kingdom Gulf war veterans. Part II: the relation of health to exposure. Occup Environ Med. 2001;58(5):299-306.
Google Scholar | Crossref | Medline9. Steele, L, Sastre, A, Gerkovich, MM, Cook, MR. Complex factors in the etiology of Gulf War illness: wartime exposures and risk factors in veteran subgroups. Environ Health Perspect. 2012;120(1):112-118.
Google Scholar | Crossref | Medline10. Boyd, KC, Hallman, WK, Wartenberg, D, Fiedler, N, Brewer, NT, Kipen, HM. Reported exposures, stressors, and life events among Gulf War registry veterans. J Occup Environ Med. 2003;45(12):1247-1256.
Google Scholar | Crossref | Medline11. Asa, PB, Cao, Y, Garry, RF. Antibodies to squalene in Gulf War syndrome. Exp Mol Pathol. 2000;68(1):55-64.
Google Scholar | Crossref | Medline12. Asa, PB, Wilson, RB, Garry, RF. Antibodies to squalene in recipients of anthrax vaccine. Exp Mol Pathol. 2002;73(1):19-27.
Google Scholar | Crossref | Medline13. Phillips, CJ, Matyas, GR, Hansen, CJ, Alving, CR, Smith, TC, Ryan, MA. Antibodies to squalene in US Navy Persian Gulf War veterans with chronic multisymptom illness. Vaccine. 2009;27(29):3921-3926.
Google Scholar | Crossref | Medline14. Golomb, BA, Nguyen, E, Dinkeloo, E. Radiation exposure predicts reported vaccine adverse effects in veterans with Gulf War illness. Int J Environ Res Public Health. 2020;17(19):7136.
Google Scholar | Crossref15. Golomb, BA. Acetylcholinesterase inhibitors and Gulf War illnesses. Proc Natl Acad Sci USA. 2008;105(11):4295-4300.
Google Scholar | Crossref | Medline16. Spencer, PS, McCauley, LA, Lapidus, JA, Lasarev, M, Joos, SK, Storzbach, D. Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans. J Occup Environ Med. 2001;43(12):1041-1056.
Google Scholar | Crossref | Medline17. Winkenwerder, W. Environmental Exposure Report. US Department of Defense; 2003.
Google Scholar18. Sullivan, K, Krengel, M, Bradford, W, et al. Neuropsychological functioning in military pesticide applicators from the Gulf War: effects on information processing speed, attention and visual memory. Neurotoxicol Teratol. 2018;65:1-13.
Google Scholar | Crossref | Medline19. Blain, PG. Organophosphorus poisoning (acute). BMJ Clin Evid. 2011;2011:2102.
Google Scholar | Medline20. Stephens, R, Sreenivasan, B. Neuropsychological effects of long-term low-level organophosphate exposure in orchard sprayers in England. Arch Environ Health. 2004;59(11):566-574.
Google Scholar | Crossref | Medline21. Chao, LL, Raymond, MR, Leo, CK, Abadjian, LR. Evidence of hippocampal structural alterations in Gulf War veterans with predicted exposure to the Khamisiyah plume. J Occup Environ Med. 2017;59(10):923-929.
Google Scholar | Crossref | Medline22. Abdel-Rahman, A, Shetty, AK, Abou-Donia, MB. Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome. Neurobiol Dis. 2002;10(3):306-326.
Google Scholar | Crossref | Medline23. Abdullah, L, Crynen, G, Reed, J, et al. Proteomic CNS profile of delayed cognitive impairment in mice exposed to Gulf War agents. Neuromolecular Med. 2011;13(4):275-288.
Google Scholar | Crossref | Medline24. Parihar, VK, Hattiangady, B, Shuai, B, Shetty, AK. Mood and memory deficits in a model of Gulf War illness are linked with reduced neurogenesis, partial neuron loss, and mild inflammation in the hippocampus. Neuropsychopharmacology. 2013;38(12):2348-2362.
Google Scholar | Crossref | Medline25. Locker, AR, Michalovicz, LT, Kelly, KA, Miller, JV, Miller, DB, O’Callaghan, JP. Corticosterone primes the neuroinflammatory response to Gulf War illness-relevant organophosphates independently of acetylcholinesterase inhibition. J Neurochem. 2017;142(3):444-455.
Google Scholar | Crossref | Medline26. Naughton, SX, Terry, AV Neurotoxicity in acute and repeated organophosphate exposure. Toxicology. 2018;408:101-112.
Google Scholar | Crossref | Medline27. Chao, LL, Rothlind, JC, Cardenas, VA, Meyerhoff, DJ, Weiner, MW. Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans. Neurotoxicology. 2010;31(5):493-501.
Google Scholar | Crossref | Medline28. Van Riper, SM, Alexander, AL, Koltyn, KF, et al. Cerebral white matter structure is disrupted in Gulf War veterans with chronic musculoskeletal pain. Pain. 2017;158(12):2364-2375.
Google Scholar | Crossref | Medline29. Cheng, CH, Koo, BB, Calderazzo, S, et al. Alterations in high-order diffusion imaging in veterans with Gulf War illness is associated with chemical weapons exposure and mild traumatic brain injury. Brain Behav Immun. 2020;89:281-290.
Google Scholar | Crossref | Medline30. Zhang, Y, Avery, T, Vakhtin, AA, et al. Brainstem atrophy in Gulf War illness. Neurotoxicology. 2020;78:71-79.
Google Scholar | Crossref | Medline31. Dickey, B, Madhu, LN, Shetty, AK. Gulf War illness: mechanisms underlying brain dysfunction and promising therapeutic strategies. Pharmacol Ther. 2020;220:107716.
Google Scholar | Crossref | Medline32. Trageser, KJ, Sebastian-Valverde, M, Naughton, SX, Pasinetti, GM. The innate immune system and inflammatory priming: potential mechanistic factors in mood disorders and Gulf War illness. Front Psychiatry. 2020;11:704.
Google Scholar | Crossref | Medline33. Warrington, R. Drug allergy: causes and desensitization. Hum Vaccin Immunother. 2012;8(10):1513-1524.
Google Scholar | Crossref | Medline34. Mokarizadeh, A, Faryabi, MR, Rezvanfar, MA, Abdollahi, M. A comprehensive review of pesticides and the immune dysregulation: mechanisms, evidence and consequences. Toxicol Mech Methods. 2015;25(4):258-278.
Google Scholar | Crossref | Medline35. Li, B, Eyer, P, Eddleston, M, Jiang, W, Schopfer, LM, Lockridge, O. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos. Toxicol Appl Pharmacol. 2013;269(3):215-225.
Google Scholar | Crossref | Medline36. John, H, van der Schans, MJ, Koller, M, et al. Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network. Forensic Toxicol. 2018;36(1):61-71.
Google Scholar | Crossref | Medline37. Noort, D, van Zuylen, A, Fidder, A, van Ommen, B, Hulst, AG. Protein adduct formation by glucuronide metabolites of permethrin. Chem Res Toxicol. 2008;21(7):1396-1406.
Google Scholar | Crossref | Medline38. Thiphom, S, Prapamontol, T, Chantara, S, et al. Determination of the pyrethroid insecticide metabolite 3-PBA in plasma and urine samples from farmer and consumer groups in northern Thailand. J Environ Sci Health B. 2014;49(1):15-22.
Google Scholar | Crossref | Medline39. Joshi, U, Pearson, A, Evans, JE, et al. A permethrin metabolite is associated with adaptive immune responses in Gulf War illness. Brain Behav Immun. 2019;81:545-559.
Google Scholar | Crossref | Medline40. Abu-Qare, AW, Abou-Donia, MB. In vitro metabolism and interactions of pyridostigmine bromide, N,N-diethyl-m-toluamide, and permethrin in human plasma and liver microsomal enzymes. Xenobiotica. 2008;38(3):294-313.
Google Scholar | Crossref | Medline41. Karlsson, I, Samuelsson, K, Simonsson, C, et al. The fate of a Hapten - from the skin to modification of macrophage migration inhibitory factor (MIF) in lymph nodes. Sci Rep. 2018;8(1):2895.
Google Scholar | Crossref42. Gefen, T, Vaya, J, Khatib, S, et al. The effect of haptens on protein-carrier immunogenicity. Immunology. 2015;144(1):116-126.
Google Scholar | Crossref | Medline43. Lanzavecchia, A. Antigen-specific interaction between T and B cells. Nature. 1985;314(6011):537-539.
Google Scholar | Crossref | Medline44. Vojdani, A, Thrasher, JD. Cellular and humoral immune abnormalities in Gulf War veterans. Environ Health Perspect. 2004;112(8):840-846.
Google Scholar | Crossref | Medline45. Johnson, GJ, Slater, BC, Leis, LA, Rector, TS, Bach, RR. Blood biomarkers of chronic inflammation in Gulf War illness. PLoS One. 2016;11(6):e0157855.
Google Scholar | Crossref46. Whistler, T, Fletcher, MA, Lonergan, W, et al. Impaired immune function in Gulf War illness. BMC Med Genomics. 2009;2:12.
Google Scholar | Crossref | Medline47. Zhang, Q, Zhou, XD, Denny, T, et al. Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome. Clin Diagn Lab Immunol. 1999;6(1):6-13.
Google Scholar | Crossref | Medline48. Campbell, JP, Guy, K, Cosgrove, C, Florida-James, GD, Simpson, RJ. Total lymphocyte CD8 expression is not a reliable marker of cytotoxic T-cell populations in human peripheral blood following an acute bout of high-intensity exercise. Brain Behav Immun. 2008;22(3):375-380.
Google Scholar | Crossref | Medline49. Everson, MP, Shi, K, Aldridge, P, Bartolucci, AA, Blackburn, WD. Immunological responses are not abnormal in symptomatic Gulf War veterans. Ann N Y Acad Sci. 2002;966:327-342.
Google Scholar | Crossref | Medline50. Skowera, A, Hotopf, M, Sawicka, E, et al. Cellular immune activation in Gulf War veterans. J Clin Immunol. 2004;24(1):66-73.
Google Scholar | Crossref | Medline51. Smylie, AL, Broderick, G, Fernandes, H, et al. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol. 2013;14:29.
Google Scholar | Crossref |

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