With substantial involvement of LIH, a German-Luxembourgish research team has developed a new test for a rare allergy related to red meat consumption: the alpha-gal syndrome. The oral provocation test currently used in clinical settings may be replaced by this novel blood test that is based on basophil activation. The findings were recently published in the prestigious Journal of Allergy and Clinical Immunology.
The thought of biting down into a juicy barbeque steak fills some with horror – and no, not only vegetarians: in 2009, American scientists confirmed that people can develop an allergy to mammalian meat. In particular, for those who have once suffered a severe inflammatory response to a tick bite, this food intolerance becomes a serious risk. Possible consequences of eating red meat then include symptoms like skin rashes, shortness of breath, or even anaphylactic shock.
The direct trigger for this rare condition, known as alpha-gal syndrome, is a highly specific sugar named galactose-alpha-1,3-galactose, or shortly alpha-gal, residing on the surface of mammalian cells but absent in humans. The allergic reaction does not start as soon as the food is chewed – as is the case with apple allergy for example – but in most cases only after a delay of two to six hours when alpha-gal reaches the bloodstream. It is therefore not easy to attribute the allergic symptoms to the consumption of meat.
The team of scientists and clinicians from Luxembourg and Germany has now developed further a far more efficient test for diagnosing alpha-gal syndrome. It has already been possible to identify a so-called sensitisation to alpha-gal, by detecting the presence of antibodies specific to alpha-gal. However, this method has never helped to estimate the actual severity of an allergic reaction. “So far, the only way to do that has been to perform a provocation test, where sufferers would eat increasingly large amounts – under medical supervision – until an allergic reaction occurred,” says the lead scientist of the project at LIH, Dr Christiane Hilger, Principal Investigator of Molecular and Translational Allergology research group in the Department of Infection and Immunity. “Because of the time delay, this test has always been very elaborate and not without risks.”
For their work, the researchers analysed the behaviour of basophils, a type of immune cells. These react strongly to various allergens, including the sugar alpha-gal, if an allergy exists. The scientists therefore further developed a test that contains, among other things, the allergen alpha-gal and certain fluorescent biomarkers. Dr Hilger explains: “Blood is drawn from the patient and brought into contact with the substances of the test kit. Next, the basophils are monitored by flow cytometry. If they have reacted strongly to alpha-gal, they light up.” To confirm their new approach, the research team studied blood samples from more than 50 patients. The results were clear, as Prof Bernadette Eberlein from the Technical University of Munich relates: “From the fluorescence signal, we were able to identify very clearly those persons who have developed a meat allergy. The test should help significantly reduce the number of provocation tests that need to be performed.”
For the scientists the work is not over. “We still know very little about the causes and immunological bases of alpha-gal syndrome,” declares Dr Hilger. “It has been observed that people tend to develop a meat allergy especially if they have had a particularly strong inflammatory response to a tick bite. We now want to find out what substances in the ticks’ saliva trigger this reaction, and exactly what goes on in the immune system.”
The research team comprised Dr Christiane Hilger, Kyra Swiontek and Prof Markus Ollert of LIH, Dr Martine Morisset and Dr. Françoise Codreanu-Morel of the Centre Hospitalier de Luxembourg (CHL), Dr Jörg Fischer of the University of Tübingen, as well as the leading participants Jana Mehlich, Prof Bernadette Eberlein and Prof Tilo Biedermann of the Technical University of Munich. The continuing project of the collaboration partners is being supported with a bilateral funding from the Luxembourg National Research Fund (FNR) and the Deutsche Forschungsgemeinschaft (DFG) in the framework of the CORE programme.
Publication: Mehlich et al., 2018, The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization. Journal of Allergy and Clinical Immunology.