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.
Akaogi
Jun
J
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
Barker
Tolga
T
Kuroda
Yoshiki
Y
Nacionales
Dina C
DC
Yamasaki
Yoshioki
Y
Stevens
Bruce R
BR
Reeves
Westley H
WH
Satoh
Minoru
M
D000596:Amino Acids; D000818:Animals; D001120:Arginine; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity; D002172:Canavanine / Q000506:poisoning*; D005260:Female; D000882:Haplorhini; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D000455:Medicago sativa / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C
D000596:Amino Acids; D001323:Autoantibodies; D002172:Canavanine; D001120:Arginine