M1 macrophages may cause more severe kidney disease in young patients
Inflammatory macrophages, a type of immune cell tasked with clearing the body of harmful invaders and dead cells, may be linked to more severe lupus nephritis in children with systemic lupus erythematosus, a small study suggests.
Those immune cells, called M1-like macrophages, appear to play a more important role in children than in adults with lupus nephritis, a disease complication marked by kidney inflammation and damage. Understanding their role could help developing treatments tailored to children with lupus.
The study, “Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney,” was published in the journal Arthritis Research & Therapy by researchers in Germany.
Macrophages have different immune system roles depending on subtype
Lupus nephritis occurs when the kidneys become inflamed and damaged due to lupus, an autoimmune disease in which the immune system mistakenly attacks the body’s healthy tissues and organs.
Some immune cells play a part in the early disease stages, whereas others are involved in how it progresses over time, for example, by keeping inflammation going. In lupus nephritis, these inflammatory cues can cause the kidneys to stop working properly.
Researchers focused on macrophages, immune cells that can play opposite roles depending on their subtype. M1 macrophages promote inflammation and are involved in tissue damage, whereas M2 macrophages work to end the inflammatory response and heal tissues.
Their study included 20 children (17 girls, three boys) with lupus nephritis and 46 children with other kidney diseases. Kidney biopsy samples were checked under the microscope for the presence of M1 and M2 macrophages.
The macrophage subtype present varied depending on the severity of lupus nephritis, the researchers found. Kidneys with signs of more severe lupus nephritis had more inflammatory M1-like macrophages, and those less severely affected had more M2-like macrophages.
On average, about half as many macrophages were found in kidney biopsies of children with lupus nephritis compared with those of adults with lupus nephritis who had taken part in a previous study. In adults, however, M2-like macrophages were the predominant subtype.
“Although M1-like macrophages play a greater role in pediatric [lupus nephritis] patients than in adult [lupus nephritis] patients, M2-like macrophages appear to be key players [in the disease],” the researchers wrote.
More M1-like macrophages and B-cells linked to poorer kidney function
Children with other kidney diseases included 15 with post-infectious glomerulonephritis, 11 with hemolytic uremic syndrome, 11 with membranoproliferative glomerulonephritis, and nine with ANCA-associated pauci-immune glomerulonephritis.
Compared with these children, kidney biopsies of those with lupus nephritis showed fewer macrophages and other inflammatory immune cells. However, the immune cell types present varied among different kidney diseases.
“Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases,” the researchers wrote.
When researchers looked at the link between the presence of different immune cells and signs of kidney disease, they found that children with more M1-like macrophages and B-cells, immune cells that produce antibodies, had poorer kidney function.
“Not only macrophage subpopulations, but also other immune cells such as CD20-positive B cells correlated positively with the severity of kidney disease,” the researchers wrote. CD20 is a protein found on the surface of B-cells.
“Macrophage-specific therapies are not yet available,” the scientists wrote. “To target macrophages therapeutically, a better understanding of the role of these cells and individual macrophage subpopulations in disease is essential.”
