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Immune Dysfunction in CFS-ME




Low NK Cell Counts, IgG Subclass Deficiencies, RNase L Dysfunction

by Maija Haavisto

Originally published by - May 2009

People with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) usually have moderate to severe immune dysfunction which may not be picked up by normal lab tests.

Some doctors believe the immune system is overactivated in CFS/ME, but there are also clear signs of immune deficiency, like low numbers of natural killer cells or NK cells. NK cells are a type of white blood cells crucial not just for prevention of infection, but cancer as well.

In the United States the illness is sometimes known as "chronic fatigue immune dysfunction syndrome" or CFIDS. In Japan the name "low natural killer cell syndrome" or LNKS has been used to describe CFS/ME. Some patients may have normal numbers of natural killer cells, but the cells do not work properly.

Another common form of immune dysfunction is immunoglobulin subclass deficiencies. There are four types of these important antibodies, IgG1, IgG2, IgG3 and IgG4. Patients with CFS/ME are most commonly deficient in IgG1 and IgG3. IgG4 values, on the other hand, may be elevated, which is suggestive of allergies.

Patients with CFS/ME have also been found to have dysfunction of the antiviral RNase L pathway. Often the activity of RNase L is dramatically increased, but many patients have an abnormal form of the RNase L molecule.

Connection with Symptoms

Immune related symptoms are common, even though not everyone with CFS/ME has them. They can include fever (chronic, intermittent or only present after exertion), pain and swelling in lymph nodes and other flu-like symptoms.

Immune dysfunction may also cause some of the fatigue and other symptoms. People with severe immunoglobulin subclass deficiencies (but without CFS/ME) often feel very fatigued and experience major improvement on intraveneous immunoglobulin therapy. RNase L function also consumes ATP, which is the primary energy source of the cells.

Some people with CFS/ME get all the colds and flus and their course is severe and prolonged, while others never seem to get any. The latter group usually reports that if they get better, they start getting colds and flus again. Both of these phenomena are caused by immune dysfunction. Some patients are also very prone to bacterial and fungal infections.



Lab Tests

Normal blood tests used to asses immune function like white blood cell counts usually do not show up abnormal in CFS/ME (although the WBC may be either low or elevated in some patients).

Usually only immunologists and infectious disease specialists test for immunoglobulin subclass deficiencies, and often they are not tested for if the total IgG levels are normal, even though one can be deficient in one or more subclasses while having normal total IgG levels.

NK cell counts and function are rarely tested for and RNase L tests are generally not available outside of research studies.

Chicken or Egg?

It is difficult to assess whether the immune dysfunction is the cause or the result of the CFS/ME. It can probably be both, at least in some cases, where patients show evidence of genetic immune deficiencies (e.g. total deficiencies of some IgG subclasses or genetic defects in complementary activation).

It is likely that often the relationship of immune dysfunction and infections is multifactorial. For example, a sudden onset of severe stress compromises the immune system which is then attacked by an enterovirus, causing an unusually severe infection that becomes chronic. The chronic infection further suppresses immunity and the patient may get further, opportunistic infections, e.g. with herpesviruses.

If the person has suffered recurrent infections (e.g. sinus infections, respiratory infections or ear infections) before the onset of CFS/ME, it is likely that congenital immune dysfunction is involved. As CFS/ME has been connected with many infectious agents, it is likely that any immune deficiencies could predispose to the illness.


Luckily, there are treatments for many of the forms of immune dysfunction in CFS/ME. NK cell dysfunction may respond to low dose naltrexone (LDN) or isoprinosine (inosine pranobex). IgG subclass deficiencies may be treated with intravenous immunoglobulin. Ampligen may help with problems related to RNase.

About the Author
Maija Haavisto is a Finnish CFS/ME patient and medical writer. She maintains the only Finnish CFS/ME website CFS-verkko and has authored the medical textbook 'Reviving the Broken Marionette:Treatments for CFS/ME and Fibromyalgia', also available in Finnish  from Finn Lectura.

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