The origin of autoimmune diseases has been revealed: it is the "hooligan" immune cells that are playing tricks

Under normal circumstances, our immune system will protect the body from external viruses, bacteria, etc When the immune system "disorderly" attacks the normal tissues, autoimmune diseases occur Autoimmune diseases are accompanied by the damage of tissues and organs and the corresponding dysfunction Photo source: Dr ofir sheen lumbroso Pathogenic autoantibodies can be found in many autoimmune diseases, but it is not known how they escape the cells of immune checkpoint Recently, a research team led by the Garvan Institute of medical research in Sydney, Australia, has found the single cells that cause autoimmune diseases from patients' samples for the first time through single cell and multi group analysis The results were published in the February 14 issue of cell DOI:https://doi.org/10.1016/j.cell.2020.01.029 Chris Goodnow, executive director of the Garvan Institute and director of the Sydney Institute of cell genomics futures, said, "currently, the treatment of autoimmune diseases is only for symptoms In order to have a more targeted treatment for the disease, we first need to understand the cause of the disease " Because "rogue" immune cells are very rare in blood samples, less than 400 cells have one, so it is very challenging to study them Mandeep Singh, the lead author of the paper, said the analysis so far only revealed "average" values for a large number of cell combinations in patient samples Using cytogenomics, we developed a way to 'amplify' the pathogenic immune cells in blood samples from four patients with cryoglobulin vasculitis " Specifically, the researchers first isolated a single cell, and then separated its genetic material, resulting in the production of "rheumatoid factors" of immune cells The protein targets healthy tissues and is associated with the most common autoimmune diseases, including rheumatoid arthritis Next, the researchers analyzed the DNA and messenger RNA of each rogue cell, scanning more than one million genomic sites in the genome to identify DNA mutations that may be the cause of the disease Through analysis, the researchers found that the pathogenic immune cells of patients with vasculitis had accumulated a large number of mutations before producing rheumatoid factors Moreover, some of the initial genetic mutations in these rogue cells can cause lymphoma "We found a 'lymphoma driven mutation', including a variant of the CARD11 gene," explained Professor Goodnow This mutation allows rogue immune cells to avoid immune tolerance checkpoints and reproduce unchecked In addition, the researchers found that cells with lymphoma driven mutations accumulated more mutations, which led to the aggregation of rheumatoid factors they produced at lower temperatures This explains why patients develop cryoglobulinemia vasculitis In these patients, rheumatoid factors in the blood gather at lower temperatures, closer to the skin, and also in kidneys, nerves, and other organs, which can damage blood vessels and are often difficult to treat The results of this study not only reveal the root cause of autoimmune diseases, but also the ability to identify and study specific immune cells with this resolution, which has great potential for the future diagnosis and treatment of all autoimmune diseases If the patients can be diagnosed in the early stage of autoimmune diseases, it is possible to combine the understanding of these mutations with the new targeted treatment of lymphoma, intervene in the progress of the disease or track the patients' response to the treatment Researchers are planning follow-up studies to study mutations in autoimmune cells in a range of other diseases, including lupus, celiac disease and type 1 diabetes reference material: