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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