Scientists at the National Institute of Allergy and Infectious Diseases (NIAID) have discovered that an especially aggressive and deadly form of a rare disorder known as hypereosinophilic syndrome (HES) can be detected with a simple blood test, rather than an expensive and time-consuming genetic test. This finding should allow doctors to diagnose the most severe form of HES early and give people with the illness the appropriate, lifesaving treatment.
To achieve this insight, the NIAID researchers put together many clues about HES, providing a better overall understanding of disease. They found that patients with HES can be separated into at least two major subgroups based on the severity and characteristics of their illness.
"This is an outstanding paper that offers new hope for people with this devastating disease," says NIAID Director Anthony S. Fauci. "As has been the case for more than five decades, NIAID's commitment to research into immune-mediated diseases continues to yield important results."
"This finding is exciting because it is unlikely that the genetic test will ever become commercially available – the disease is just too rare," says Amy D. Klion, a clinical researcher and lead author of the study. "For many patients, a blood test for the enzyme tryptase may be the best chance for a timely diagnosis." Dr. Klion conducted the study with Thomas B. Nutman, of NIAID, and colleagues at the National Institutes of Health Clinical Center.
HES is a systemic disease of unknown cause characterized by an overabundance of white blood cells called eosinophils. The eosinophils invade major organs such as the heart, lungs, brain and nerves, causing organ damage and sometimes organ failure that leads to death. The disease usually responds to steroid treatment.
Scientists knew that a severe form of HES existed. They had discovered several important pieces of information about it, but they had yet to assemble these pieces into a coherent picture. For example, scientists knew that some patients with HES had much more extensive organ damage and did not respond to steroid treatment. More recently, researchers found that some cases of HES were associated with a genetic glitch that causes two genes to fuse together. Furthermore, an already existing drug, imatinib, was found to counteract the effects this genetic glitch.
Through a detailed study of 15 HES patients over eight years, the NIAID team discovered crucial new pieces of the puzzle and put them together. Most importantly, they found that nine study patients had increased numbers of abnormal mast cells (a type of immune system cell) and markedly increased blood levels of tryptase, an enzyme mast cells produce. However, these patients, all male, did not show other signs of mastocytosis, a disease marked by overproduction of mast cells. In addition, the nine patients had more severe organ damage than the other six and did not respond well to steroids. They did, however, respond to imatinib.
Finally, five patients from each group were genetically tested. All of the individuals with elevated tryptase levels turned up positive for the previously described genetic glitch. None of the patients with normal tryptase levels did.
The NIAID team concluded that they had identified a special type of HES that includes an underlying mast cell disorder. This more severe form of the disease, likely caused in part by the fused genes, can be identified at an early stage with a tryptase blood test and then successfully treated with imatinib.
"The patients in our study showed a spectacular response with imatinib," says Dr. Klion. "One hundred percent of the patients treated with this drug responded."