Pathogenesis of HTLV-I-associated inflammation: Exploration through therapeutic intervention

HAM/TSP是一种慢性脊髓疾病，由一种名为HTLV-I的病毒引起。全世界约有2000万人受到感染，其中许多人在英联邦成员国。感染HTLV-I型病毒是终生的，大约3%的人会患上这种慢性衰弱疾病，其中一半人会对轮椅产生依赖。我们和其他人已经在携带者和HAM/TSP患者中显示出对HTLV-I的强烈和持久的免疫反应，但这无法清除病毒。然而，血液中病毒负担较低的携带者患疾病的风险较低。这些携带者的免疫反应似乎更能杀死受感染的细胞。效率较低的反应与较高的病毒负担有关，病毒负担推动免疫反应，导致免疫细胞释放化学物质，无意中造成伤害，尤其是对脊髓细胞的伤害。我们对HAM/TSP的理解表明，针对免疫反应应该改善我们患者的健康，特别是如果疾病被早期诊断的话。为了确定最佳治疗类型，我们计划进行三项药物研究，以不同的方式针对免疫反应。每一种都被用于其他炎症条件，但以前从未在HAM/TSP中研究过。我们的目标是研究临床反应的范围和持续时间，并将其与治疗对免疫反应和血液中HTLV-I感染细胞数量的不同影响联系起来。这反过来将提高我们对这种疾病的认识和理解，并应导致更好的治疗。我们的结果将通过时事通讯与患者分享，并在诊所网站上提供。

HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected, many in member states of the Commonwealth. Infection with HTLV-I is lifelong, and about 3% will develop this chronic debilitating disease, of which half will become wheelchair dependent. We, and others, have shown a strong and persistent immune response to HTLV-I in carriers and patients with HAM/TSP, but this fails to clear the virus. However, carriers with a low burden of virus in the blood have a low risk of developing disease. The immune response in these carriers seems better able to kill infected cells. A less efficient response is associated with a higher viral burden that drives the immune response with a resultant release of chemicals by the immune cells that inadvertently cause harm, most especially to cells in the spinal cord. Our understanding of HAM/TSP suggests that targeting the immune response should improve the health of our patients especially if the disease is diagnosed early. To identify the best type of treatment we are planning three studies of drugs that target the immune response in different ways. Each has been used in other inflammatory conditions but never before studied in HAM/TSP. We aim to study the extent and duration of the clinical response and to associatedthis with the different effects that the therapies have on the immune response and on the number of HTLV-I infected cells in the blood. This in turn will improve our knowledge and understanding of the disease and should lead to better therapy. Our results will be shared with our patients through a newsletter and made available on the clinic website.