Academic journal article Environmental Health Perspectives

Cellular and Humoral Immune Abnormalities in Gulf War Veterans

Academic journal article Environmental Health Perspectives

Cellular and Humoral Immune Abnormalities in Gulf War Veterans

Article excerpt

We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed mitogen (PWM); level of immune complexes; myelin basic protein (MBP) and striated and smooth muscle autoantibodies; and antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1), HSV-2, human herpes Type 6 (HHV-6), and Varicella zoster virus (VZV). The percentage ofT cells in patients versus controls was not significantly different, whereas a significantly higher proportion of patients had elevated T cells compared with controls. The percentage of B cells was significantly elevated in the patients versus the controls. The NK cell (NK) activity was significantly decreased in the patients (24.8 [+ or -] 16.5 lyric units) versus the controls (37.3 [+ or -] 26.4 lytic units). The percentage of patients with lower than normal response to PHA and PWM was significantly different from controls. Immune complexes were significantly increased in the patients (53.1 [+ or -] 18.6, mean [+ or -] SD) versus controls (34.6 [+ or -] 14.3). Autoantibody titers directed against MBP and striated or smooth muscle were significantly greater in patients versus controls. Finally, the patients had significantly greater titers of antibodies to the viruses compared with the controls (p < 0.001). These immune alterations were detected 2-8 years after participation in the Gulf War. The immune alterations are consistent with exposure to different environmental factors. We conclude that Gulf War syndrome is a multifaceted illness with immune function alterations that may be induced by various factors and are probably associated with chronic fatigue syndrome. Key words: autoantibodies, B cell, Gulf War syndrome, immune complexes, natural killer cell, T cell. Environ Health Perspect 112:840-846 (2004). doi:10.1289/ehp.6881 available via http://dx.doi.org/[Online 17 February 2004]

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Veterans returning from the Gulf War of 1990-1991 described multiple-organ symptoms that included chemical sensitivity, chronic fatigue, fibromyalgia, neurocognitive deficits, irritable bowel syndrome, headaches, joint pains, fever, and a general unwellness, referred to as Gulf War syndrome (GWS) (Cherry et al. 2001; Gray et al. 2002; Haley and Kurt 1997; Hallman et al. 2003; Iowa Persian Gulf Study Group 1997; Kang et al. 2002; Kroenke et al. 1998; Lashof and Cassells 1998). GWS probably has a multiple-factorial etiology involving possible chemical exposures (Haley and Kurt 1997). The suspected factors include Arabian sand dust, low-level chemical and biological warfare agents, pyridostigmine bromide, N,N-diethyl-m-toluamide, organophosphate pesticides, depleted uranium, combustion by-products of oil well fires, diesel exhaust, petroleum products, and infectious agents (Abou-Donia et al. 2001; Kurt 1998; Moss 2001; Schumm et al. 2002; Sharabi et al. 1991). Explanations for GWS include genetic polymorphism of paraoxonase (PON1) (Haley et al. 1999; La Du et al. 2001), butyrylcholinesterase (Shen 1998), glutathione S-transferase and cytochrome P4[50.sub.1][A.sub.1] (Whatt et al. 2000), and, more recently, neuropathy target esterase (Winrow et al. 2003). Clinical findings include abnormalities of basal ganglia and brainstem (Haley et al. 2000) and recently reported increased neurologic diseases and, particularly, an increased rate of amyotrophic lateral sclerosis (ALS) (Haley 2003; Homer et al. 2003). Moreover, Gulf War Veterans have an increase in serum RNAs with segments homologous to chromosome 22q11.2 ALU, indicating a rearrangement of this antigen-responsive spot (Urnovitz et al. 1999).

The symptoms of GWS are remarkably similar to those of chronically ill individuals with immunologic alterations after exposure to chlorinated pesticides (McConnachie and Zahalsky 1991, 1992), chlorpyrifos (Thrasher et al. …

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