Some doctors believe the immune system is overactivated in Chronic Fatigue (CFS)/Fibromyalgia, 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. They are our “garbage men” and “police men” of the immune system.
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. 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 are most commonly deficient in IgG1 and IgG3. IgG4 values, on the other hand, may be elevated, which is suggestive of allergies or an autoimmune issue.
Patients with CFS 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 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) 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 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.
Normal blood tests used to asses immune function like white blood cell counts usually do not show up abnormal in CFS (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. 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 a virus, 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 Epstein Barr, Cytomegalovirus, Herpes Virus (HHV6). If the person has suffered recurrent infections (e.g. sinus infections, respiratory infections or ear infections) before the onset of CFS, it is likely that congenital immune dysfunction is involved. As CFS 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. NK cell dysfunction may respond to low dose naltrexone (LDN) or isoprinosine (inosine pranobex). IgG subclass deficiencies may be treated with intramuscular or intravenous immunoglobulin. Ampligen may help with problems related to RNase L.
Regardless of the underlying immune imbalance and associated infections, the primary goal is to first uncover these dysfunctions and infections and begin a proper course of treatment.
Hypercoagulable State in CFS and FM
New research is indicating that many chronic fatigue syndrome and fibromyalgia patients are in a state of low level activation of the coagulation system and treatment of this coagulation activation can result in a complete or partial resolution of symptoms. Studies have found that approximately 80% of chronic fatigue syndrome and fibromyalgia patients have this low level activation of the clotting system. This low level activation does not produce a blood clot, but rather an intermediate substance called a soluble fibrin monomer (SFM). This coats the inside of the blood vessel and limits oxygen and nutrient flow into the cells, resulting in the symptoms of CFS and FMS including fatigue, muscle pain, brain fog and sleep disturbances. It has been found that 40% of CFS/FMS patients have a genetic predisposition for the production of too much SFM, while 50% have a genetic predisposition that limits the breakdown of the SFM. Both conditions result in excessive SFM coating of the blood vessels.
This genetic predisposition can be set into action by a number of factors, including trauma, exposure to heavy metals, toxins, pesticides and chronic molds and viral, yeast and bacterial infections, including Epstein Bar Virus (EBV), Cytomegalovirus (CMV), HHV6, Parvovirus, Enterovirus, Mycoplasma, Chlamydia Pneumonia and Lyme’s disease. The SFM coating not only limits the oxygen and nutrient flow, but it also provides a place for the virus, yeast and bacterial to “hide” and escape destruction by the immune system. Thus, it is very difficult for CFS/FMS patients to rid the body of these infections when compared to healthy individuals.
Diagnosis is made by the use of a specialized test called an ISAC (Immune System Activation of Clotting) panel, which measures soluble fibrin monomer, fibrinogen, prothrombin fragment 1+ 2, plasminogen activator inhibitor 1, and thrombin/antithrombin complexes. Treatment includes low dose heparin and substances to break up the fibrin as well as elimination of the initiating agent, whether it is a virus, bacteria, yeast or toxin. Intervention can be from several weeks to a number of months, with potentially dramatic improvements occuring with treatment and sometimes complete resolution of symptoms.