New insights into ankylosing spondylitis
Auto-immune diseases are pathological deviations of the immune system - here, the body's own immune system inadvertently attacks its own body. Bekhterev's disease is one such auto-immune disorder. Now, scientists at Jacobs University in Bremen have deciphered the molecular mechanisms of the disease in more detail.
Ankylosing spondylitis leads to prolonged and painful Inflammation of the joints and ultimately to a deformation of the Spine. Researchers suspect that the cause of the disease is a specific protein that most patients have in their cells: the HLA-B27 protein. Proteins fold into a three-dimensional structure after they are produced, and researchers suspect that this the HLA-B27 protein triggers the disease due to its particularly slow and complicated folding.
Transport of the HLA-B27 protein studied
Researchers at Jacobs University, in collaboration with colleagues at Freie Universität Berlin, have now found out exactly how this folding and the subsequent quality control of the HLA-B27 protein take place. Dr. Zeynep Hein, a postdoc in the research group of Prof. Dr. Sebastian Springer at Jacobs University, has studied the transport of the HLA-B27 protein within human cells in detail.
For this purpose, a genetically stabilized form of the HLA-B27 protein is produced and compared with the protein found in our body. "We have always been interested in the transport of proteins in cells and are skilled at making artificial proteins to study the transport process that way," Hein says. "This project put those skills and knowledge to good use." The experiments will be conducted in cell culture, i.e., not involving patients.
Among other things, Hein and her team were able to find out that the HLA-B27 protein has great difficulty folding into its special structure. And even if it can fold, the protein tends to disintegrate again right away, thereby losing its function. "Of course, at this point, we can't say exactly how these basic findings will later lead to a possible Therapy or cure ankylosing spondylitis," says Springer. But one thing he and his team have been aware of for some time, he says: "Exploring fundamental mechanisms is essential to ultimately develop therapies and drugs."
Source:
Zeynep Hein, Britta Borchert, Esam Tolba Abualrous, Sebastian Springer: Distinct mechanisms survey the structural integrity of HLA-B*27:05 intracellularly and at the surface. PLOS ONE (2018), doi:10.1371/journal.pone.0200811.
Text: Jacobs University Bremen
