Role of non-protein amino acid l-canavanine in autoimmunity

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.