McGrath H
Veterans Administration, New Orleans, LA, USA.
Lupus. 2017 Oct;26(12):1239-1251. doi: 10.1177/0961203317707064. Epub 2017 May 8.
Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.
系统性红斑狼疮（狼疮，SLE）是一种慢性自身免疫性疾病，其特征是产生自身抗体，这些抗体与抗原结合并沉积在组织内以固定补体，导致广泛的全身炎症。本文提出的研究结果表明，超极化的、三磷酸腺苷（ATP）缺乏的线粒体是疾病进程的核心。这些超极化的线粒体抵抗激活诱导的凋亡所需的去极化。线粒体ATP缺乏加剧了这种对凋亡的抵抗，也减少了清除凋亡小体所需的巨噬细胞能量。在这两种情况下，都会导致坏死，即细胞死亡的替代途径。细胞内成分泄漏到血液和组织中，引发针对其清除的炎症反应。结果就是“自身免疫”。紫外线（UV）-A1光子有能力纠正这种异常。外源性低剂量全身UV-A1辐射会产生单线态氧。单线态氧在狼疮患者中有两种主要的缓解作用，而UV-A1光子本身还有其他几种作用。单线态氧使超极化的线粒体去极化，触发非ATP依赖性凋亡，从而阻止坏死。其次，单线态氧激活编码血红素加氧酶（HO-1）的基因，HO-1是全身稳态的主要调节因子。HO-1催化氧化剂血红素降解为胆绿素（转化为胆红素）、铁和一氧化碳（CO），其中前三种发挥强大的抗氧化作用，与第四种CO一起，保护冠状动脉、中枢神经系统和肺部免受损伤。UV-A1光子本身通过降低B细胞活性、防止细胞介导免疫的抑制、减缓向SLE的表观遗传进展以及改善盘状和亚急性皮肤狼疮，直接减轻狼疮病情。最后，这些机制的组合降低了抗心磷脂抗体水平，并在狼疮妊娠期间起到保护作用。最重要的是，UV-A1照射是一种基本无害、易于管理且舒适的治疗手段。
