Okadaic acid-like toxin in systemic lupus erythematosus patients: hypothesis for toxin-induced pathology, immune dysregulation, and transactivation of herpesviruses.
Preliminary evidence suggests there is a toxin in the sera of systemic lupus erythematosus patients which reacts with a commercial enzyme-linked immunosorbent assay kit for the detection of the marine toxin, okadaic acid. Data is presented which supports the hypothesis that an okadaic acid-like toxin may be the principle agent of lymphocyte dysregulation in systemic lupus erythematosus and other immune-dysregulated states. The okadaic acid-like toxin can produce the specific abnormalities in T-lymphocyte phenotype and function typical of systemic lupus erythematosus, principally through its ability to inhibit serine/threonine phosphatases necessary for secondary signalling processes and through its ability to inhibit calcium which is crucial to protein kinase C-mediated signalling of T-lymphocytes. The disruption probably occurs through the protein tyrosine kinase p56lck pathway crucial for IL-2. Additionally, the toxin's ability to disrupt voltage-sensitive ion channels in cell membranes may be responsible for the multi-organ pathology observed in systemic lupus erythematosus patients, particularly neurological, cardiac and nephritic. Data from a different study conducted by the author suggests that latent and persistent viruses are reactivated in active lupus. This activation could be the result of the toxin's ability to act as an immune modulator, or its ability to act as a transactivating factor.
Mitchell
T M
TM
University of Southern California, Los Angeles 90089, USA.
D006564:Herpesviridae / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008954:Models, Biological; D019319:Okadaic Acid / Q000097:blood*; D014118:Toxins, Biological / Q000097:blood*; D015533:Transcriptional Activation
D014118:Toxins, Biological; D019319:Okadaic Acid