Immune Macrophages Play Key Role in Kidney Inflammation in AAV

New study sheds light on effect of different immune cell types

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A person drinks a glass of water, which is important for the proper function of the kidneys, highlighted here.

Immune macrophages or cells that carry the proteins CD163 and/or CD206 play a key role in kidney inflammation in people with ANCA-associated vasculitis (AAV), a study reported.

Researchers found that these distinct macrophages contribute to the inflammatory process in different ways.

Moreover, the team determined that both CD163 and CD206 have predictive value: While CD163 protein in the urine signaled active kidney inflammation in AAV patients, CD206 protein in the bloodstream may predict clinical outcomes, such as end-stage kidney disease and mortality.

The study, “CD163 and CD206 expression define distinct macrophage subsets involved in active ANCA-associated glomerulonephritis,” was published in the Journal of Autoimmunity.

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A person drinks a glass of water, which is important for the proper function of the kidneys, highlighted here.

Kidney Impairment Likely Where Rheumatoid Arthritis, AAV Coexist

AAV is a group of autoimmune disorders marked by inflammation and damage to small blood vessels, especially in the kidneys and lungs. Up to 70% of all AAV patients develop glomerulonephritis, an inflammatory condition that affects the tiny filters in the kidneys, and requires immediate treatment to prevent kidney damage.

Because some patients still progress to end-stage kidney disease (kidney failure), there is a need to understand the mechanisms underlying inflammation in AAV-related glomerulonephritis.

CD163 and CD206 in kidney inflammation

Macrophages are a type of immune cell thought to be involved in AAV-related glomerulonephritis. These cells have different functions — from amplifying the body’s inflammatory responses and eliminating invading microbes to promoting tissue repair. As a result, different types of macrophages are expected to play different roles in glomerulonephritis.

One way to distinguish between different macrophage subtypes is by the presence of different proteins. Macrophages with the proteins CD163 and CD206 have been found in lesions associated with glomerulonephritis, but the clinical significance of these cells has not been investigated.

To learn more, researchers in the Netherlands and Ireland collected clinical data, as well as blood and urine samples, from 210 AAV patients at three clinical sites. The patients from the different sites were identified as groups 1, 2, and 3.

Among the participants, 134 had AAV with glomerulonephritis, 24 had AAV without glomerulonephritis, and 52 were in remission. Nine healthy people also were included as controls.

The analysis revealed that AAV patients with active glomerulonephritis had significantly higher levels of urinary CD163 compared with those without glomerulonephritis and participants who were in remission across all groups.

Blood levels of CD206 also were elevated in active glomerulonephritis patients compared with those who were in remission, but the differences in group 1 were non-significant. Notably, CD206 levels in blood declined significantly after patients reached remission.

In all groups, urinary CD163 was highly specific, meaning CD163 levels could rule out glomerulonephritis. Its sensitivity, or ability to confirm the presence of glomerulonephritis, was lower, however.

Combining urinary CD163 results with blood CD206 increased the sensitivity, but at the same time, lowered the specificity of the diagnosis.

“Thus, combining both markers did not significantly improve diagnostic accuracy when compared to [urinary] CD163 alone,” the researchers wrote.

Next, the team assessed the presence of macrophages with CD163 and/or CD206 in kidney tissue. Macrophages with CD163 alone were most abundant in the glomeruli — the kidneys’ filtering units — whereas CD206 macrophages and double-positive cells were predominantly detected in the tissue surrounding the glomeruli, called the tubulointerstitium.

This “strengthens our notion that CD206 is expressed [produced] mainly in tubulointerstitial areas, whereas CD163 expression locates in both glomerular and tubulointerstitial areas,” the researchers wrote.

Both blood CD206 and urinary CD163 levels correlated strongly with CD163 in glomerular and tubulointerstitial tissue, and less so with CD206. CD163 in glomeruli, but not CD206, and CD163 and CD206 in tubulointerstitium, were found to correlate with abnormal glomeruli, suggesting that different macrophage subtypes contribute to the inflammatory process in AAV-related glomerulonephritis.

Regarding clinical outcomes, a higher percentage of CD163 macrophages in glomeruli correlated with higher creatinine levels in the blood — a sign of kidney impairment. Predictors of end-stage kidney disease included blood creatinine levels during periods of active disease, urinary CD163, blood CD206, a change in creatinine levels at remission, glomerulonephritis scores, and the percentage of abnormal glomeruli. No factors predicted AAV relapse.

Patients with active AAV who died during follow-up had higher levels of CD206 in the bloodstream compared with those who did not. After adjusting for age and blood creatinine levels, researchers found that age and blood CD206 levels predicted mortality.

“Our results confirm that CD206-[positive] and CD163-[positive] macrophages are prominent components of the cellular infiltrate in ANCA [glomerulonephritis],” the researchers wrote. “We found distinct macrophage phenotypes [characteristics] which may play a distinct role in the immunopathology in ANCA [glomerulonephritis].”

“[Urinary] CD163 remains an excellent marker to detect active ANCA [glomerulonephritis], whereas [blood] CD206 may be important for risk prediction,” the team concluded.