Department of Pathophysiology, Medical School, University of Athens, Greece.
Cancer and Inflammation Program, National Cancer Institute, Bethesda, MD, USA.
J Autoimmun. 2017 Mar;78:1-10. doi: 10.1016/j.jaut.2016.12.011. Epub 2017 Jan 9.
Systemic lupus is the prototypic human autoimmune disease. It is a kaleidoscope of autoreactivities, with clear indications of both a genetic and environmental basis. Indeed, it is a disease that can manifest in virtually every tissue and organ and can also be found spontaneously in a number of animal species, including dogs, cats and horses. Moreover, there are multiple murine models of lupus, the first of which, New Zealand Black (NZB) mice, were discovered in 1959. Despite an enormous effort from scientists in multiple disciplines, the etiology of lupus remains elusive and the introduction of new therapies has been disappointing. Fortunately, significant advances have occurred to help patients through the general principles of internal medicine, including antibiotics, dialysis, and of course use of steroids and immunosuppressive agents. However, the magic bullet has yet to be discovered. One of the major causes of morbidity in lupus remains lupus nephritis and there has been significant effort and encouragement in understanding the pathogenesis, renal histologic classification, and use of therapeutic protocols to induce and sustain remission of lupus nephritis. Indeed, the first use of evidence-based clinical trials in lupus was initiated by Dr. Alfred D. Steinberg at NIH in pioneering studies involving either oral or intravenous pulses of cyclophosphamide, azathioprine or corticosteroids alone and/or some combination. Cyclophosphamide intravenously proved to be superior and the use of cyclophosphamide in combination with methylprednisolone remained the standard protocol for the treatment of lupus nephritis for decades. Although alternative therapies have been introduced, including mycophenolate mofetil, the use of therapies first pioneered at NIH may still be considered standard of care in the appropriate indications. More targeted therapies are much desired. In this review we provide a comprehensive overview of lupus nephritis and the evolution of clinical treatments.
系统性红斑狼疮是典型的人类自身免疫性疾病。它是自身反应的万花筒，具有明确的遗传和环境基础。事实上，它是一种几乎可以在所有组织和器官中表现出来的疾病，也可以在许多动物物种中自发发现，包括狗、猫和马。此外，还有多种狼疮的鼠类模型，其中第一个模型，即新西兰黑（NZB）小鼠，于 1959 年被发现。尽管来自多个学科的科学家付出了巨大的努力，但狼疮的病因仍然难以捉摸，新疗法的引入也令人失望。幸运的是，已经取得了重大进展，通过内科的一般原则，包括抗生素、透析，当然还有类固醇和免疫抑制剂的使用，来帮助患者。然而，还没有发现灵丹妙药。狼疮的主要致残原因之一仍然是狼疮肾炎，人们在理解发病机制、肾脏组织学分类以及使用治疗方案诱导和维持狼疮肾炎缓解方面付出了巨大努力并受到鼓舞。事实上，在狼疮中首次使用循证临床试验是由 NIH 的 Alfred D. Steinberg 博士发起的，他在开创性的研究中涉及单独使用口服或静脉环磷酰胺、硫唑嘌呤或皮质类固醇，或某些组合。静脉内注射环磷酰胺被证明是优越的，环磷酰胺联合甲基强的松龙的使用仍然是治疗狼疮肾炎几十年的标准方案。尽管已经引入了替代疗法，包括霉酚酸酯，但在适当的适应症中，仍可考虑 NIH 首次开创的疗法作为标准治疗。更有针对性的治疗方法是非常需要的。在这篇综述中，我们全面概述了狼疮肾炎和临床治疗的演变。
