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Update on HHV-6 and CFS Research from the National CFIDS Foundation

  [ 66 votes ]   [ Discuss This Article ]
By Gail Kansky, National CFIDS Foundation • • June 22, 2001

Editor's Note: This article appears courtesy of Gail Kansky, an association for CFS - and is used with permission.

After years of connecting the dots and researching CFS/ME (myalgic encephalomyelitis) through medical journals, unpublished data, and patents, Professor Alan M. Cocchetto, Associate Professor at SUNY (State University of New York), believes he has uncovered more data that he hopes will help to unravel some additional mysteries surrounding this disease. The NCF has sent his paper explaining these hypotheses to a handful of researchers world-wide in hopes that foregoing publication of this information will speed up appropriate therapy.

His intense research over months and years has implicated CFS/ME as a serious illness that can create life-threatening conditions. Ironically, this new data is solidified most by medical research previously reported on CFS/ME patients in Europe.

HHV-6 related discovery

The professor's conclusions point to patients with active human herpesvirus-6 (HHV-6) infection, and perhaps other infections as well, [who] suffer from a condition known as Acquired Angioedema. Acquired Angioedema is associated with lymphoproliferative disorders and is due to a deficiency of Complement C1-Esterase Inhibitor (C1-INH). He believes that HHV-6 creates this deficiency via C1-INH consumption - the results of which are explained in detail in documents distributed to the researchers.

Cocchetto uncovered documents from the US, Japan, and Germany that confirmed a connection between HHV-6 infection and alterations in several key components of complement including C1-esterase inhibitor. C1-I NH is a protease inhibitor present in the plasma, which controls the activation of the first complement component, C1, and inactivates its sub-components C1r and C1s. It also inhibits other serine proteases of coagulation and fibrinolytic and contact systems, like kallikrein, plasmin-activated Hageman factor and factor XIa. Deficiencies in C1-INH can be associated with severe pathologies that may even be fatal.

Acquired C1-INH deficiencies or acquired angioedema are due to an abnormally high catabolism of the inhibitor or to the presence of auto-antibodies. The disease appears as facial edema, edema on extremities, on intestinal walls and in the higher respiratory tract. Cocchetto commented "Yamanishi's group, from Japan, found that complement C1 was important in HHV-6 infections. If you couple this with the fact that German researcher's already looked at this in 375 patients and found it to be significant among their HHV-6 patients, then I feel this is certainly worth pursuing. Any profound alteration in this complement component will compromise the host's immunity."

Furthermore, after disclosure was made to the NCF, Cocchetto himself had the testing done. "Since I was one of the first patients tested for HHV-6A by Dr. Donald Carrigan and Dr. Konstance Knox at ViraCor Diagnostic Labs (then known as HerpesVirus Diagnostic Labs), I felt compelled, given the evidence I found, to be tested for C1-INH. Sure enough, I tested positive for this (abnormally low values are considered positive). My hopes are that his moves appropriate research forward"

Several medical publications indicate that androgen therapy (Danazol and Stanazolol) as well as anticoagulants have been used to help address this problem. A C1-esterase inhibitor is currently being evaluated by researchers at the Mayo Clinic and by scientists at the University of Iowa.

Ironically, the US is the only country that has yet to approve its use in patients. It is currently in FDA trials for use in patients with hereditary angioedema. Since C1 lies upstream from other complement components, it may create a domino effect and cause coagulation and other problems for the host. Current medical literature suggests that this is one means by which viruses commandeer the host's immune system.

CFS/ME Research Discovery

In another discovery, Cocchetto found that a scientist from the Glaxo Group in England made a highly significant discovery in CFS/ME. He found that variations in the Arginine-VasoPressin Receptor gene-2 (AVPR2) could be used to see if any person has a susceptability to CFS/ME. The patent states that arginine-vasopressin plays a major role in water metabolism, which includes both "water loading" and "water deprivation." It goes on to explain the clinical profound overlap between CFS/ME and Serum Inappropriate Anti-Diuretic Hormone. The work references that of the late and greatly missed researcher, Dr. David Streeten.

Glaxo's treatments included fludrocortisone, the drug tried by many who have low-blood volume but rarely tolerated, as well as a new AVPR2 antagonist that would be useful in this disease. The last discovery of Cocchetto's was an article about abnormal water metabolism in patients with CFS/ME.

In a previous publication by researchers in Scotland, the scientists reported that patients with CFS/ME excreted 62% of a water load vs. 97% excretion of the water load in healthy subjects. Likewise, the baseline plasma arginine-vasopressin levels in patients were reported to be significantly lower than in healthy controls. Thus patients showed evidence of increased total body water content.

This study is highly significant due to the fact that the excretion of a water load in CFS/ME patients constitutes a hyponatremic condition. This work appears to complement the discovery made by Glaxo scientists. For those physicians who would like to test their patients now for C1-esterase inhibitor deficiency or acquired angiodema and for those patients who would like to ask their physicians to test them, Speciality Laboratories, in California, has the following blood tests that may be ordered: #1529 (angioedema evaluation), #1615 (Complement C1q), #1501 (Complement C3), #1504 (Complement C4). The number for physicians is 1-800-421-4449. The entire medical information packet, discussed in this article, is being made available to medical researchers. Interested physicians are asked to contact (the NCF) office for further information.

It is our hope at the NCF that this important research work may be expanded upon to enable patients to live a better quality-of-life. We hope that we may be able to fund research activity that directly pertains to these problems. The NCF is indebted to Professor Cocchetto for his years of investigational work.

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