Potential Hope for CFIDS/ME Patients with ICL

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This is from the newsletter archives of the National CFIDS

Foundation. http://www.ncf-net.org/archive.htm

They have many interesting articles there. And have funded a lot of helpful

research.

blessings

Shan

Potential Hope for CFIDS/ME Patients with ICL

http://www.ncf-net.org/forum/HopewithICL-Fall05.htm

by Alan Cocchetto, NCF Medical Director ©2005

Over a decade ago, Dr. Cheney, Dr. Komaroff and other CFIDS/ME

physicians had identified a condition known as ICL in some of their patients.

ICL is the acronym for " Idiopathic CD4 Lymphocytopenia " and it denotes a

dramatic loss of a specific T-cell lymphocyte known as a CD4 (T-helper) cell.

The

extensive reduction in CD4 cells is a hallmark characteristic of AIDS, a

disease characterized by a progressive loss of function of the immune system.

Scientists at Enzon Pharmaceuticals have been studying the mechanisms involved

in

CD4 depletion and have developed a potential drug treatment for CD4 T-cell

lymphopenia. Since ICL is typically defined as a CD4 cell count below 200

cells/microliter, a condition that unfortunately is present in some CFIDS/ME

patients,

this treatment may offer a means to restore some of the immune dysfunction

that has occurred as a result of the disease process. More importantly, it may

provide a way to reduce opportunistic infections that often accompany this

illness since CD4 cells are critical to appropriate immunologic response.

The NCF believes that scientific evidence points to CFIDS/ME as a result of a

chronic infection. As such, the immune system is chronically activated due

to this " unknown " infection. As a consequence, this cellular activation must

therefore play a vital role in the pathology of this disease. Abnormal levels

of RNaseL, cellular apoptosis, etc. have been reported in CFIDS/ME and this

bolsters our beliefs here. Thus, a chronic infection certainly has the

potential to cause cellular depletion, as is seen in ICL, via T-cell apoptosis.

Scientists have discovered that some patients with ICL have a deficiency in an

important enzyme known as adenosine deaminase.

A deficiency of adenosine deaminase (ADA) results in severe combined

immunodeficiency (SCID) in humans. ADA is an enzyme in the purine degradation

pathway

that deaminates adenosine and deoxyadenosine to yield inosine and

deoxyinosine respectively. The enzyme has a wide tissue distribution with the

highest

activity occurring in lymphocytes. ADA deficiency inhibits the normal catabolism

of purines and results in the accumulation of metabolic substrates that are

especially toxic to lymphocytes. ADA deficiency results in T-cell apoptosis

(cell death) as well as an alteration to T-cell differentiation and therefore an

alteration in the production of mature T-cells.

The good news is that a suggested drug treatment for ADA deficiency is

Adagen. Adagen (intramuscular injection) is a modified enzyme used for enzyme

replacement therapy for the treatment of SCID associated with ADA deficiency.

Adagen provides specific and direct replacement of the deficient enzyme. Adagen

administration can eliminate the toxic metabolites of ADA deficiency and result

in improved immune function. However, it is imperative that treatment with

Adagen be carefully monitored by measurement of the level of ADA activity in

plasma. Monitoring of the level of deoxyadenosine triphosphate (dATP) in

erythrocytes is also helpful in determining that the dose of Adagen is adequate.

The NCF is confident that PWC/ME patients that suffer from ICL will be

encouraged by this information.

References:

1. p53 expression is required for thymocyte apoptosis induced by adenosine

deaminase deficiency; Benveniste P, Cohen A; Proc Natl Acad Sci 1995, Aug

29;92(18):8373-7

2. Adenosine deaminase and thymocyte maturation; Doherty PJ, Pan S, Mulloy

JC, E, Thorner P, Barankiewiecz J, Roifman CM, Cohen A; Scand J

Immunol 1991, Apr; 33(4):405-10

3. Mechanisms of apoptosis in developing thymocytes as revealed by adenosine

deaminase-deficient fetal thymic organ cultures; LF, Vaughn JG,

t AB, Blackburn MR, Van De Wiele CJ; Biochem Pharmacol 2003, Oct

15;66(8):1595-9

4. Fundamental Immunology; Raven Press; - editor

5. Osler's Web: Inside the labyrinth of the Chronic Fatigue Syndrome

Epidemic; Hillary ; Crown Publishers, 1996

6. Adagen injection PDR drug information;

http://www.drugs.com/PDR/Adagen_Injection.html

7. Method of treating CD4+ T cell lymphopenia in immuno-compromised

patients; US Patent #5,728,560 issued March 17, 1998 to Inventors: Shorr RGL,

MA, Goddard DH; Assignee: Enzon, Inc.

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