Autoimmunity in Post-Traumatic Stress Disorder

创伤后应激障碍中的自身免疫

• 批准号: 9892288
• 负责人: Robert Hal Scofield
• 金额: --
• 依托单位: OKLAHOMA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892288
• 关键词: Afghanistan; Antibodies; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocytes; Clinical; Clinical Research; Control Groups; Craniocerebral Trauma; Data; Disease; Exposure to; Future; Genes; Human; Human Resources; Hyperactive behavior; Immune; Immune system; Immunization; Immunoblast; Infection; Influenza vaccination; Interferons; Interleukin-17; Lymphocyte; Marines; Measurement; Medical; Memory B-Lymphocyte; Mental Depression; Mental disorders; Monoclonal Antibodies; Multiple Sclerosis; Paper; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Population; Post-Traumatic Stress Disorders; Prevalence; Production; Psychiatric Diagnosis; Publishing; Recombinants; Research; Research Personnel; Research Subjects; Rheumatism; Rheumatoid Arthritis; Risk; Services; Sjogren' s Syndrome; Specificity; Study Subject; System; Systemic Lupus Erythematosus; T-Lymphocyte; Techniques; Traumatic Brain Injury; Veterans; War; Work; autoimmune thyroid disease; cohort; combat; ds-DNA; exposed human population; mild traumatic brain injury; monoclonal antibody production; peripheral blood; recruit

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.

创伤后应激障碍 (PTSD) 是暴露于创伤情境的人类的常见问题 与美国武装部队人员作战的风险高达 25%。因此，PTSD 是一个主要的医学问题 退伍军人事务部的医疗系统。创伤后应激障碍 (PTSD) 患者存在其他医疗风险 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和 多发性硬化症。此外，在外周血中发现异常大量的 Th17 T 细胞。 这些患者的 IL-17 水平也很高。 Th17 T 细胞对于多种自身免疫性疾病的发病机制至关重要 疾病，外周血单核细胞（PMBC）中干扰素基因表达增加 在 PTSD 发作之前，这种情况也见于自身免疫性疾病。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 患者处于 自身免疫性疾病的风险增加，即使没有临床试验，其血清中也会存在自身抗体 自身免疫性疾病。初步数据表明这是正确的。我们研究了 20 名 PTSD 患者并进行了比较 这些患者中有 20 名患有轻度脑外伤的患者。他们都是阿富汗战争的退伍军人。我们找到了 3 个 的 PTSD 受试者具有高滴度自身抗体——其中一个是抗 Ro，另一个是抗 RNP，另一个是抗 RNP 三分之一的人检测出抗 dsDNA，另外 6 人的 ANA 呈阳性。此外，我们还发现自身免疫性风湿病 137 名患有 PTSD 和轻度创伤性脑损伤 (TBI) 的受试者的疾病增加，而患有 PTSD 和轻度创伤性脑损伤 (TBI) 的受试者中有 92 名 仅 TBI。因此，考虑到已发表的有关免疫异常和自身免疫性疾病的数据 创伤后应激障碍（PTSD）以及我们的初步数据表明，拟议的研究有一个令人信服的前提。我们将学习 患有 PTSD 的受试者，将这些结果与具有其他精神科诊断的匹配受试者进行比较，以及 没有精神病学诊断、抑郁症和创伤性脑损伤得到控制的受试者。我们将追求三个具体目标。 首先，我们将确定 PTSD 受试者的血清中是否存在自身抗体，以及是否存在 自身抗体与干扰素特征相关。在第二个目标中，我们将确定是否存在 PTSD 中的多克隆 B 细胞过度活跃。第三个目标是确定 PBMC 表型是否异常 与自身抗体的存在有关。