Journal of IiME Volume 6 Issue 1 (June 2012) Drs Paul Cheney and Charles Lapp said: “Immunologic tests have been frequently applied to patients with (ME)CFS in part because they are frequently abnormal and in part because the signs and symptoms of (ME)CFS can be explained as a consequence of immunologic dysfunction….We propose a set of tests that look for evidence of T-cell activation along with discrete immune defects….Immune tests become more valuable when used as an array or set of tests used to determine a pattern of immune dysfunction” Dr Jay Goldstein noted that “The sed rate (erythrocyte sedimentation rate or ESR) is often very low” (an important observation because many physicians dismiss ME/CFS as an infectious disease unless there is a high ESR, but if inflammatory processes are activated in other ways, the ESR can remain normal or low, which does not exclude an inflammatory illness); “Immune complexes and positive anti-nuclear antibodies are encountered very frequently….Elevated levels of various cytokines and their receptors are often seen”. Professor Nancy Klimas said: “Our group in Miami has been actively working to better understand CFIDS since 1985. This work has focused on the immunologic abnormalities seen in the majority of patients (and) has helped to develop a sense of diagnostic certainty in the evaluation of CFIDS patients, as well as to identify subgroups that are immunologically different from the majority of CFIDS patients evaluated….We have found the immune evaluation to be … important, as it not only helps classify the patients, but also helps to direct the care of the patient….Such an evaluation must touch on three points: (1) level of T cell activation….while there are many markers of T cell activation…the most sensitive in CFIDS is CD3+CD26+ phenotype by flow cytometry, the T cell expressing transferrin receptor. In ‘normals’, about 18 percent of circulating T cells express this activation marker, while CFIDS patients show double to triple these levels of activation. Other phenotypic markers help to fill out the picture. CD8+DR, or activated cytotoxic cells, are elevated in the majority of patients with recent exacerbations but seem to normalise during healthier times. (2) diminished cell Invest in ME (Charity Nr. 1114035) function….CFIDS patients have diminished T and B cell function in response to cell activators (mitogens) in culture. The most sensitive is diminished response to pokeweed mitogen (PWM), which reflects poor T and B cell interaction. Even more remarkable is the very poor ability of NK cells to kill virally infected target cells in culture…People with CFIDS often have very diminished NK cell function….While we routinely look at both mitogen response and NK cytotoxicity, I believe assessing NK cytotoxicity is more important. We also routinely assess B cell function by looking at immunoglobulin production. Basically this is accomplished by looking at total immunoglobulins (IgG, IgA, IgM), at IgG subclasses (IgG. IgG2, IgG3, IgG4)….(3) evidence of viral reactivation. Serology for common reactivation viruses…adds further evidence that the immune dysfunction now quantified is of a serious enough nature to cause secondary viral reactivation….The Miami group’s enthusiasm and excitement are based on …our understanding of the underlying immune defects are finally sharply focused. This clear understanding of the immune disorder is driving new therapeutic approaches”. Professor Anthony Komaroff said: “Our studies indicate that two additional tests are elevated more often in patients with CFIDS: immune complexes and immunoglobulin G (IgG)”. Dr Benjamin Natelson (Professor of Neurosciences at the University of Medicine and Dentistry, New Jersey) said: “The major lab tests I check are those indexing immunological dysfunction. I do a standard immunological profile, including circulating immune complexes, complement levels and IgG subclasses. I have found a rough correlation between disability and the number of these tests that are positive….Being able to report such examples of immune dysfunction is often of practical value in assisting the severely ill CFS patient in obtaining disability (payment)”. 1992 On 2nd – 4th October 1992 the First Biennial International Research conference on (ME)CFS was held at Albany, New York. It was reported in the CFIDS Chronicle, Summer 1993; pages 64 – 72. www.investinme.org Page 42 of 108

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