Autoimmunity in Post-Traumatic Stress Disorder

创伤后应激障碍(PTSD)是暴露在创伤环境中的人类的常见问题 打击风险高达25%的美国武装部队人员。因此，创伤后应激障碍是一个主要的医学问题 退伍军人事务部的医疗系统。患有创伤后应激障碍的患者有其他医疗风险 问题包括系统性红斑狼疮、类风湿性关节炎、自身免疫性甲状腺疾病，以及 多发性硬化症。此外，在儿童外周血中发现异常高数量的Th17T细胞。 这些患者的IL-17水平都很高。Th17T细胞在几种自身免疫性疾病的发病机制中起关键作用 疾病，外周血单个核细胞(PMBC)干扰素基因表达增加 在创伤后应激障碍发作之前，这种情况也出现在自身免疫性疾病中。数据表明，自身抗体 比临床疾病早很多年，甚至几十年。因此，我们假设PTSD患者，他们处于 自身免疫性疾病的风险增加，即使在没有临床症状的情况下，他们的血清中也会出现自身抗体 自身免疫性疾病。初步数据显示，这是正确的。我们研究了20名创伤后应激障碍患者，并将 这些患者中有20名为轻度脑外伤患者。所有人都是阿富汗战争的退伍军人。我们发现了3个 的PTSD患者有高滴度的自身抗体--抗Ro抗体1例，抗RNP抗体2例，抗RNP抗体1例 1例抗dsDNA抗体阳性，6例抗核抗体阳性。此外，我们发现自身免疫性风湿病 与92例PTSD和轻度创伤性脑损伤(TBI)患者相比，137名PTSD和轻度创伤性脑损伤(TBI)患者的疾病增加 仅限TBI。因此，考虑到发表的关于免疫异常和自身免疫性疾病的数据， 创伤后应激障碍与我们的初步数据一起，对拟议的研究有一个令人信服的前提。我们会研究 患有创伤后应激障碍的受试者，将这些结果与有其他精神疾病诊断的匹配受试者以及 对于没有精神疾病诊断的受试者，控制抑郁症和脑外伤。我们将追求三个具体目标。 首先，我们将确定创伤后应激障碍患者的血清中是否存在自身抗体，以及是否存在 自身抗体与干扰素信号有关。在第二个目标中，我们将确定是否有 多克隆B细胞在创伤后应激障碍中的作用。在第三个目标中，我们将确定异常的PBMC表型 与自身抗体的存在有关。

Post-traumatic stress disorder (PTSD) is a common problem in humans exposed to traumatic situations with combat US Armed Services personnel having a risk of up to 25%. Thus, PTSD is a major medical problem for the medical system of the Department of Veterans Affairs. Patients with PTSD carry risk of other medical problems, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and multiple sclerosis. In addition, abnormally high numbers of Th17 T cells are found in the peripheral blood of these patients as are high levels of IL-17. Th17 T cells are critical for the pathogenesis of several autoimmune diseases, and there is increased expression of interferon genes in peripheral blood mononuclear cells (PMBC) prior to onset of PTSD, a condition also seen in autoimmune disease. Data indicate that autoantibodies precede clinical disease by many years, even decades. Thus, we hypothesize that PTSD patients, who are at increased risk of autoimmune disease, will have autoantibodies present in their sera even without clinical autoimmune disease. Preliminary data suggest this is correct. We studied 20 PTSD patients and compared these to 20 patients with mild traumatic brain injury. All were Afghanistan War combat veterans. We found 3 of the PTSD subjects had high titer autoantibodies – anti-Ro in one, anti-RNP in another and anti-RNP with anti-dsDNA in a third, while another 6 had a positive ANA. In addition, we found autoimmune rheumatic disease increased among 137 subjects with PTSD and mild traumatic brain injury (TBI) compared to 92 with TBI only. Thus, considering the published data concerning immune abnormalities and autoimmune disease in PTSD along with our preliminary data, there is a compelling premise to the proposed studies. We will study subjects with PTSD, comparing these results to matched subjects with other psychiatric diagnoses as well as to subjects with no psychiatric diagnosis, controlled for depression and TBI. We will pursue three specific aims. First, we will determine whether autoantibodies are present in the sera of PTSD subjects and if presence of autoantibodies correlates with the interferon signature. In a second aim we will determine whether there is polyclonal B cell hyperactivity in PTSD. In the third aim we will determine whether abnormal PBMC phenotype is associated with the presence of autoantibody.