Akaogi Jun, Barker Tolga, Kuroda Yoshiki, Nacionales Dina C, Yamasaki Yoshioki, Stevens Bruce R, Reeves Westley H, Satoh Minoru
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
Autoimmun Rev. 2006 Jul;5(6):429-35. doi: 10.1016/j.autrev.2005.12.004. Epub 2005 Dec 29.
Association of SLE and alfalfa was first reported in a volunteer who developed lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia study. This was corroborated with studies in monkeys fed with alfalfa sprout that developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine homologue L-canavanine, present in alfalfa, was suspected as a cause. L-canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during protein synthesis. Aberrant canavanyl proteins have disrupted structure and functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few cases remains controversial. Epidemiological studies on the relationship between alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L-canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were negative. L-canavanine incorporation may be more efficient in the presence of inflammation or other conditions that can cause arginine deficiency. The L-canavanine induced apoptotic cells can be phagocytosed and a source of autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are ubiquitinated and processed via proteasome. Incorporation of L-canavanine into proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L-canavanine-induced lupus will be an interesting model of autoimmunity induced by the modification of self-proteins at the translational level.
系统性红斑狼疮（SLE）与苜蓿的关联最早是在一名志愿者身上报道的，该志愿者在为一项高胆固醇血症研究摄入苜蓿籽时出现了狼疮样自身免疫。在喂食苜蓿芽的猴子身上进行的研究证实了这一点，这些猴子患上了SLE。用L-刀豆氨酸再次激发会使疾病复发。怀疑存在于苜蓿中的精氨酸同系物L-刀豆氨酸是病因。L-刀豆氨酸可被精氨酰tRNA合成酶充电，在蛋白质合成过程中取代L-精氨酸。异常的刀豆氨酸蛋白结构和功能受到破坏。少数病例报告的苜蓿片诱发或加重SLE仍存在争议。关于苜蓿与SLE关系的流行病学研究很少。在小鼠中，喂食L-刀豆氨酸的NZB/W F1、NZB和DBA/2小鼠的SLE病情加重/发作，然而，对BALB/c小鼠的研究结果为阴性。在存在炎症或其他可导致精氨酸缺乏的条件下，L-刀豆氨酸的掺入可能更有效。L-刀豆氨酸诱导的凋亡细胞可被吞噬，是内体蛋白酶加工自身抗原的来源。内源性刀豆氨酸蛋白被泛素化并通过蛋白酶体加工。L-刀豆氨酸掺入蛋白酶体或内体也会导致抗原加工的破坏。苜蓿/L-刀豆氨酸诱导的狼疮将是一个在翻译水平上通过自身蛋白质修饰诱导自身免疫的有趣模型。
