Belgian research groups from the VIB, Ghent University, Ghent University Hospital, and the biotech company Argenx have solved a century-long puzzle about the presence of protein crystals in asthma. Normally, proteins do not crystallize in the body, but there are some instances when this process does occur. Charcot-Leyden crystals are made from the protein galectin-10 and were discover in the airways of asthmatics as early as 1853.
In 1853, Jean-Martin Charcot at the renown Salpetriere Hospital in Paris report detail sketches of bipyramidal crystals that he had observe in the sputum of patients suffering from asthma, an observation also made by Ernst von Leyden in 1872. These crystalline deposits became widely know as Charcot-Leyden crystals (CLCs) in the medical world.
Since then, they have describe in widespread chronic allergic and inflammatory diseases; so such as asthma, bronchitis, allergic rhinitis and rhinosinusitis. It was, however, only during the last couple of decades that scientists confirm the content of CLCs was up of galectin-10; so finally settling debates that last for nearly a century and a half.
Galectin-10 is one of the most abundant proteins in eosinophils; which help to mount an inflammatory response in humans. Surprisingly, Gal10 remains largely soluble in eosinophils and it only forms crystals; so once it has release as part of an immunological defense. The function of Gal10 also remain elusive.
Technical challenges to test
The scientists overcame many technical challenges to test this idea. They had to find a way to produce millions of crystals of Gal10 in the laboratory for research purposes; also establish that these were identical to CLCs found in patients. The researchers use patient derive crystals to determine; so the three dimensional structure of Gal10 down to the atomic scale. This provide a long-sought answer confirming that experimentally produce CLCs are identical to patient derive CLC.
The researchers found that Gal10 induce a fully blown immune response only when it was in the crystalline state. In solution, Gal10 was harmless. Most importantly, crystalline Gal10 in the form of Charcot-Leyden crystals induce key features of asthma; so including the production of alter mucus that is a big problem for most asthmatics. Thus, the study already deliver a major breakthrough with crystal clear conclusions.
Prof. Bart Lambrecht said, “Our research results were unexpect and crystal-clear at the same time. They was completely struck by the fact that antibodies can rapidly dissolve CLCs; so that are so abundantly present in the native mucus of patients. Although more tests are need, the data in mouse models suggest that use of these antibodies; which could be a very effective way of reducing excessive inflammation and mucus accumulation in the lungs of patients with asthma.