From the latest Phoenix Rising Newsletter Natural Killer Cell Function is Depressed in Gulf War Illness. Toni Whistler, Mary Fletcher, W. Loneragan, S. Vernon and Nancy Klimas. Toni Whistler was excited – I could hear it in her voice. She was reporting on natural killer cell (NK) functioning in Gulf War Syndrome (GWS) patients. She had put them through an exercise stress test and then measured their NK cell functioning. She wanted to make it clear how important she felt exercise tests were. She stated it twice. Both times I could hear her voice rise as she emphatically stated that "challenge studies (e.g. exercise tests/stress tests) are critical for finding differences between chronic fatigue syndrome patients and controls;" i.e., to get strong results you’re probably to have to whack your patients pretty hard. Natural killer cells man the lines of our first immune response. They troll about inspecting cells to see if they’re defective or infected or cancerous. If they find a bad cell, they kill it and raise the alarm. We know the natural killer cells are not tracking down and killing infected cells like they should in this disease and it appears (unfortunately) that, at least in some patients, they’re not tracking down cancerous cells either. This study took natural killer cell research to the next level; they examined the gene expression (gene activity) before and after exercise to see if different genes were active in the GWS and healthy controls. The need for a stress test of some sort is really no secret - the research community is finally catching on to a pattern that's been obvious for some time now. Studies that measure patients at baseline (at rest) often do not have positive results but studies that somehow stress whatever system they’re studying often do. Dr. Whistler also underscored a broader need that came up again and again during the conference and reached a peak with Dr. Vernon’s address - the need for research standards in this disease. Why do an exercise test for a study on natural killer cell functioning? Apparently NK cells spill out of the lymphoid organs (lymph nodes, spleen) and rush into the blood when we exercise. They obviously do that for a reason. Staci Stevens has suggested that the post-exertional malaise in ME/CFS could be due to immune dysfunction . One wonders if that immune dysfunction somehow involves malfunctioning NK cells. Networking Gone Awry - What are they trying to get at? One suspects gene networks that influence natural killer cell activity. Dr. Vernon recently published a paper suggesting that immune cells network differently in chronic fatigue syndrome patients. Instead of the efficient, streamlined immune networks found in healthy people she found large fragmented networks in ME/CFS patients. Essentially those large well integrated networks of immune cells that work together to produce a powerful immune response just aren’t found in many ME/CFS patients. This study found that 49 genes involved in NK cell function had increased activity in the healthy controls but only nine genes had increased activity in the GWS patients. This suggests that a big chunk of the essential gene activity needed for a healthy NK cell response is just not occurring in GWS (or ME/CFS). (Dr. Whistler stated that the two groups are essentially similar) Interestingly, the activity of the gene for perforin - the shells that make up the NK cell's heavy artillery - was lower in GWS patients. Low perforin levels have been a hallmark finding in ME/CFS. A Natural Killer Cell Disease? The Fletcher/Klimas team in Miami started this work about 20 years ago and the closer they’ve looked the more they’ve found. Thus far they’ve been the only research team to take this on. (Why the CDC has never incorporated NK cell studies into their research is puzzling. They have never gone so far (so far as I can tell) as to measure the activity of a single natural killer cell in all their studies). Now the Whittemore-Peterson Institute is stepping into the gap. Later in the conference Dr. Mikovits will pinpoint a defect in the natural killer cells in Dr. Peterson’s Reno cohort that could prevent them from identifying infected cells . Natural killer cell problems appeared to be at the heart of the immune dysfunction in many ME/CFS patients. Collaboration Works! This study was an excellent example of the kind of collaborative effort Dr. Vernon has been proposing (and initiating at the CAA). It included researchers from the CDC (Dr. Whistler), the CFIDS Association of America (Dr. Vernon) and Fletcher/Klimas team in Miami. Given Dr. Whistler’s affiliation with the CDC – the same group that relegated the post-exertional fatigue symptom to irrelevance in their latest definition - it was startling to hear her make the call for more exercise stress tests. One wonders how far her views will carry at that group.