Autoimmunity in Post-Traumatic Stress Disorder

创伤后应激障碍中的自身免疫

• 批准号: 10704565
• 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/10704565
• 关键词: Afghanistan; Antibodies; Autoantibodies; Autoantigens; Autoimmune; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Clinical; Clinical Research; Control Groups; Craniocerebral Trauma; Data; Disease; Exposure to; Future; Genes; Human; Human Resources; Hyperactivity; IL17 gene; Immune; Immune system; Immunization; Immunoblast; Infection; Influenza vaccination; Interferons; 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; United States Department of Veterans Affairs; Veterans; War; Work; autoimmune rheumatologic disease; autoimmune thyroid disease; cohort; combat; combat veteran; comparison control; 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）是一种常见的问题，在人类暴露于创伤的情况下， 与美国武装部队人员作战的风险高达25%。因此，PTSD是一个主要的医疗问题， 退伍军人事务部的医疗系统。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， 多发性硬化此外，在受试者的外周血中发现异常高数量的Th 17 T细胞。 这些患者的IL-17水平很高。Th 17 T细胞是几种自身免疫性疾病发病机制的关键。 疾病，并且外周血单核细胞（PMBC）中干扰素基因的表达增加 在PTSD发病之前，PTSD是一种在自身免疫性疾病中也可见的病症。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，谁是在 自身免疫性疾病的风险增加，将有自身抗体存在于他们的血清中，即使没有临床 自身免疫性疾病初步数据表明这是正确的。我们研究了20名创伤后应激障碍患者， 20例轻度创伤性脑损伤患者。他们都是阿富汗战争的退伍军人。我们找到3个 的PTSD受试者有高滴度的自身抗体-一个是抗Ro，另一个是抗RNP， 抗dsDNA抗体阳性1例，抗核抗体阳性6例。此外，我们发现自身免疫性风湿性关节炎 在137名患有PTSD和轻度创伤性脑损伤（TBI）的受试者中， 仅TBI。因此，考虑到已发表的关于免疫异常和自身免疫性疾病的数据， 创伤后应激障碍沿着我们的初步数据，有一个令人信服的前提，提出的研究。我们将研究 受试者与创伤后应激障碍，比较这些结果与匹配的受试者与其他精神病诊断，以及 没有精神病诊断的受试者，控制抑郁症和TBI。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 自身抗体与干扰素信号相关。在第二个目标中，我们将确定是否存在 PTSD中多克隆B细胞过度活跃。在第三个目标中，我们将确定是否异常PBMC表型 与自身抗体的存在有关。