Similarly to rheumatoid arthritis, spondyloarthritis (SpA) is a type of chronic inflammatory disease that predominately affects the joints: Ankylosing spondylitis and psoriatic arthritis being the most common forms. SpA affects not only the joints, but also leads to damage to other tissues like the skin and intestine.
Researchers in the Griseri group, using an in vivo model of SpA, revealed that the inflammatory cytokine GM-CSF (granulocyte-macrophage colony stimulating factor) was a key driver of joint and intestinal inflammation. Published in Nature Communications, the study found that one of the ways that GM-CSF exerts its pathogenic effect is by boosting the production of inflammatory white blood cells in the bone marrow, especially neutrophils – a type of white blood cell that protects the body from infections but can also be tissue-toxic when it accumulates in excess. GM-CSF was able to do so not only by promoting the activity of neutrophil progenitor cells, but also that of the upstream "mother cells" of the blood: the haematopoietic stem cells.
The study also revealed a new pathogenic mechanism in SpA as highly proliferative neutrophil progenitor cells accumulated in the bone marrow and also, more surprisingly, directly inside the inflamed joints.
The study highlights GM-CSF as an interesting therapeutic target in SpA, especially as GM-CSF producing cells have been shown to be increased in patients suffering from spondyloarthritis, and as the antibody mediated blockade of GM-CSF activity in rheumatoid arthritis has been shown to be safe and effective in clinical trials.
The work was supported by funding from Versus Arthritis.