The so-called Charcot-Leyden crystals (CDCs), named after the two scientists who first studied them in 1856 and 1872, are found in the airways of patients with asthma as well as other ailments of the respiratory system such as bronchitis or sinusitis. But until now, medical science has been unsure of the crystals’ role in the disease process.
Now, a team of researchers from the Flemish Institute for Biotechnology and the university of Ghent set out to find out if the CDCs were responsible for over-stimulating the immune system in the lungs, provoking an immune reaction and inflammation. The crystals are known to be composed of Gal10, one of the proteins contained in eosinophils – cells which cause an infectious reaction.
“Every doctor learns about Charcot-Leyden crystals, and associates them with the presence of eosinophils,”said lead researcher Professor Bart Lambrechts in a statement. “They are often found in the sputum of asthma patients, especially in severe forms. And yet no-one knew what the crystals did and why they were found where they are.”
The team, he explained, hypothesised that the CDCs could have a similar effect in the lungs to crystals of uric acid in the joints of sufferers from gout. The team was able to study the crystals at atomic level to discover the 3D structure of the Gal10 protein.
“This is the first time in medical history that these crystals have been studied at atomic resolution,” said Professor Savvas Savvides, co-leader of the project. The crystals are only a few thousandths of a millimetre in size, and this is the first time they have survived the difficult transfer from a hospital patient to the specialist X-ray facility. “What’s more, they provided us with a beautiful 3D structure of the molecules in the crystals,” Prof. Savvides said.
In the final analysis, the team discovered that Gal10 is harmless in a dissolved state. It is only when it forms crystals that it has an effect of causing a thickening of the mucus layer in the airways, which leads to shortness of breath in the patient.
The researchers have now teamed up with the Ghent-based biotechnology company argenx to create antibodies which react to CDCs, dissolving the crystals and rendering the Gal10 harmless once again. The work is still at the laboratory stage, being tested on mice, but the results are promising, producing a noticeable effect in a matter of hours.
“It was an abracadabra moment,” Prof. Savvides said. “I have spent 25 years growing protein crystals, and suddenly I could see how they might be dissolved. Furthermore we could actually visualise the process to see how the magic of the antibodies works.”
The Brussels Times