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Okadaic Acid-like Toxin Found in Lupus

by Alan Cocchetto, NCF Medical Director  2005
 
Scientific data has provided evidence to suggest that a toxin-like
substance is present in the sera of patients with lupus. This
toxin reacts with a commercial assay for okadaic acid, a marine toxin.
Okadaic acid has been shown to disrupt numerous biological
systems in humans.
 
Dr. Teri Mitchell, a researcher from the University of Southern
California, had brought forth medical evidence that an okadaic
acid-like substance was found in lupus. Dr. Mitchell had published this
research in the journal Medical Hypotheses in 1996. What
the NCF found particularly intriguing is that Dr. Mitchell's effort
provided the perfect scientific corollary to the ciguatoxin-like
substance (ciguatera epitope) that had been found in CFIDS/ME patients by
Dr. Yoshitsugi Hokama at the University of Hawaii. As
you should recall, Dr. Hokama had published his preliminary findings in
several medical journals and others are currently anticipated
since his manuscripts have been submitted for peer review.

Okadaic acid is a toxic polyether which has been derived from a marine
dinoflagellate. It is among a group of marine toxins that
are known to cause fish and shellfish poisoning in mammals. Marine
toxins cause symptoms ranging from diarrhea to death. In
scientific experiments using a commercial competition enzyme-linked
immunosorbent assay (ELISA), Dr. Mitchell determined that
the sera of lupus patients contained a substance that reacted with the
okadaic acid anti-idiotypic antibody. This sera included
patients who suffered with active and inactive disease. Samples were
obtained from Cedars-Sinai Medical Center.
 
Since marine toxins exert their toxic effect through the disruption of
voltage-sensitive ion channels, this disruption is capable of
inducing multi-organ pathology due to the fact that these ion channels
are present in cell membranes. Thus, these types of toxins
have the capacity to alter critical cellular processes particularly in
relation to ion channel dependent kidney, heart, lung and brain
functions. In Dr. Mitchell's paper, she had mentioned that there was a
published report that a researcher working in proximity to
tanks of dinoflagellates, that produce marine toxins, suffered extreme
neurological impairment, erratic heartbeats and altered blood
pressure. This implies exposure and the consequences of such an exposure
as a cause and effect. In addition, Dr. Mitchell showed
that okadaic acid affects the production of cytokines and that this is
consistent with the aberrations that are seen in lupus. Interestingly,
Dr. Mitchell commented on and referenced the work of Dr. Hokama in her
paper!
 
Perhaps one of the most disturbing findings is that this okadaic
acid-like toxin is capable of serious immune disruption due to the
fact that okadaic acid is a phosphatase inhibitor and it can mimic
the protein phosphorylation patterns of several cytokines through
the induction of specific genes. The modulation of these genes causes
alterations in lymphocyte signaling as well as changes in their
growth, proliferation and cytotoxicity. These types of changes to
T-cells can have a profound impact on the hosts ability to fight
infection and because of this impact, the toxin ? immune connection is
very important.
 
Dr. Mitchell also commented that this okadaic acid-like toxin is capable
of activating latent and persistent viruses in lupus. In fact,
her focus is on the reactivation of herpes viruses by this toxin. This
is particularly intriguing since herpes reactivation is seen in
CFIDS/ME patients as well. However, one final comment Dr. Mitchell made in
her paper should catch the eyes of all CIDS/ME
patients: A variation of this hypothesis may be applicable to other
diseases, including chronic fatigue immune dysfunction syndrome
(CFIDS) and AIDS. There you have it ? CFIDS! The NCF feels very
fortunate to have located this research and as such, we have
forwarded this to Dr. Hokama and his team for their review. We are
encouraged by this corollary to our ciguatera epitope research
since it adds to the depth of our scientific knowledge base.
 
Reference:
Okadaic acid-like toxin in systemic lupus erythematosus patients:
hypothesis for toxin-induced pathology, immune dysregulation,
and transactivation of herpes viruses; Mitchell TM; Med Hypotheses 1996
Sep;47(3):217-25


[Ed. Note: A letter was posted to CFIDS/ME patients, physicians and CFIDS/ME groups worldwide in late June on the internet.  It said:

"Though research, initiated by the National CFIDS Foundation (NCF), on the ciguatera epitope has been published in peer-reviewed medical journals, there has been reluctance on the part of some patients, physicians and patient groups alike to embrace the concept and to acknowledge the importance of the presence of a ciguatera toxin-like substance found in CFIDS/ME patient sera by Dr. Yoshitsugi Hokama at the University of Hawaii's John A. Burns School of Medicine.  As you know, the basis for this laboratory discovery was initially made by Dr. W. John Martin and was previously reported upon by the NCF in an investigative report.

     "The NCF believes that the ciguatera epitope plays a critically important role in the CFIDS/ME disease process and in fact, it provides research clues as to the structural relationship of this epitope to the primary underlying pathogen that has eluded scientists for decades.  As such, the NCF has funded additional research to assess the pathogenic relationship of this epitope. 

     "Recently, the NCF found a significant research paper that confirmed the functional corollary to the ciguatera epitope found in CFIDS/ME patients.  This paper, titled "Okadaic acid-like toxin in systemic lupus erythematosus patients: hypothesis for toxin-induced pathology, immune dysregulation, and transactivation of herpesviruses" was published in Medical Hypothesis in 1996 by a medical researcher at the University of Southern California.  The NCF believes that this paper provides a sound foundational basis for CFIDS/ME pathology involving the ciguatera epitope.

     "As such, the NCF will be providing additional details and discussion in the next edition of its National Forum newsletter as well as updating its website to reflect this latest information.  Patients wishing to donate to the NCF's research grant program can donate online via our website or by sending the donation directly to our office.  All donations go directly to research with no percentage held back."

     The article above is intended to give our members much needed hope as well as showing the direction of our research funding  seems to be right on track and is coming closer to disclosing all the "mysterious" entities of this disease as well what to do about it.  Thank you for helping us to reach this point.]

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