CD206 in Certain White Blood Cells May Be AAV Treatment Target
Study finds people with active disease had higher levels of CD206 in their kidneys
Monocytes, a type of white blood cell, that carry a protein called CD206 are found at abnormally high levels in the blood of people with active ANCA-associated vasculitis (AAV), a study has found.
This held true even when researchers compared people with AAV who had glomerulonephritis, a condition in which the tiny filter units inside the kidneys (the glomeruli) become damaged, to individuals with similar kidney function.
People with AAV had higher levels of CD206 in their kidneys, perhaps lying on the surface of macrophages. These macrophages originate from monocytes that leave blood circulation to enter into tissues, where they may play a role in inflammation.
“CD206 might be involved in the pathogenesis [disease mechanisms] of AAV and may be a potential target for the disease,” researchers wrote.
The study, “CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis,” was published in the journal BMC Immunology.
AAV occurs when the immune system goes awry and turns against the small blood vessels in the body, leading to inflammation. When inflammation hits the kidneys, it may damage the glomeruli. As a result, the kidneys may not be able to work well enough to filter and remove waste products and extra water out of the body.
What exactly causes damage to the glomeruli is unclear, but immune macrophages can release substances that contribute to inflammation.
Previous research has shown that macrophages rich in CD206 may gather in the kidney’s tubulointerstitium, which comprises the tubules and the tissue surrounding the glomeruli.
Macrophages go round about tissues, patrolling for germs or eliminating old or dead cells. They do this by carrying scavenger receptors on their surface, which recognize molecular patterns that signal danger or germs. CD206 is one such scavenger receptor.
CD206 might be involved in the pathogenesis [disease mechanisms] of AAV and may be a potential target for the disease
Researchers study 14 people with active microscopic polyangiitis
What researchers in China have now worked out is how CD206 is linked to active disease in people with AAV. Their study included 14 people who had active AAV and a mean age of 68.9 years. All had microscopic polyangiitis (MPA), a type of AAV.
The researchers drew on data from 13 people with remissive AAV who had no disease activity to serve as controls. Eleven had MPA, one had kidney-limited vasculitis, and one had granulomatosis with polyangiitis. They also recruited nine healthy individuals and nine other kidney function-adjusted controls.
The proportion of blood monocytes that carried CD206 was about three times higher in people with active AAV than in those with remissive disease (12.6% vs. 4.3%).
These monocytes also circulated in higher numbers in people with active AAV than in healthy individuals or in those with similar kidney function.
When the researchers looked at the kidney’s tissues, they observed that CD206 was found at much higher levels in the damaged glomeruli and tubulointerstitium of people with active AAV than in disease controls.
While CD206 usually sits on a cell’s surface, it can be cleaved to form soluble CD206. The blood levels of soluble CD260 were more than three times higher in people with active AAV than in those who had no disease activity or were healthy.
One of the main types of self-reactive antibodies seen in AAV patients target a protein called myeloperoxidase (MPO). In their next set of experiments, the researchers used macrophages derived from mouse bone marrow cells or human blood cells that were either left untreated or treated with anti-MPO antibodies.
Treatment with anti-MPO antibodies increased the levels of CD206 in both kinds of macrophages. But when AZD5904, an inhibitor of MPO, was also added, the effect was blocked.
These findings suggest that AAV antibodies may be able to increase the levels of CD206, and that this protein — or the cells that carry it — “could be a potential target,” the researchers wrote.
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