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）是经历创伤状况的人类常见问题 与我们的武装服务人员作斗争，风险高达25％。那是PTSD是一个主要的医疗问题 退伍军人事务部的医疗系统。 PTSD患者承担其他医疗的风险 问题，包括全身性红斑狼疮，类风湿关节炎，自身免疫性甲状腺疾病和 多发性硬化症。另外，在中的最高数量的Th17 T细胞中发现 这些患者是高水平的IL-17。 Th17 T细胞对于几种自身免疫性的发病机理至关重要 疾病，外周血单核细胞中干扰素基因的表达增加（PMBC） PTSD发作之前，在自身免疫性疾病中也出现了这种疾病。数据表明自身抗体 在临床疾病之前，甚至数十年。那就是我们假设在 自身免疫性疾病的风险增加，即使没有临床，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 这些对20例轻度创伤性脑损伤患者。所有人都是阿富汗战争的退伍军人。我们找到了3 PTSD受试者的具有高滴度自动抗体 - 一个抗RO，另一个抗RNP，另一个抗RNP和抗RNP 三分之一的抗DSDNA，另有6个为正ANA。此外，我们发现自身免疫性风湿病 137名PTSD和轻度脑损伤（TBI）的受试者中，疾病增加了，而92名 仅TBI。考虑到有关免疫异常和自身免疫性疾病的已发表的数据 PTSD以及我们的初步数据，对拟议的研究具有令人信服的信念。我们将学习 具有PTSD的受试者，将这些结果与其他精神诊断的受试者进行比较 对于没有精神病诊断的受试者，受抑郁和TBI的控制。我们将追求三个具体目标。 首先，我们将确定在PTSD受试者的血清中是否存在自身抗体，如果存在 自身抗体与干扰素签名相关。在第二个目标中，我们将确定是否存在 PTSD中的多克隆B细胞多动症。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。