Biological markers, or biomarkers, are measurable indicators that reflect biological processes. They help diagnose, monitor, or predict disease risk and understand connections between environmental factors and human diseases. Biomarkers range from common measurements like blood pressure to complex analyses of genes or proteins. CD163 is one such biological marker gaining attention for its role in health and disease.
Understanding CD163
CD163 is a protein that functions as a scavenger receptor, helping cells “clean up” certain substances. It belongs to the SRCR superfamily and is found primarily on monocytes and macrophages, which are types of immune cells.
It is particularly abundant on M2 macrophages, a subtype known for anti-inflammatory and tissue-repairing functions. A primary role involves binding to hemoglobin-haptoglobin complexes, formed when red blood cells break down. This binding allows for their internalization and degradation, preventing oxidative damage to tissues.
CD163 and Inflammation
CD163 plays a significant role in the body’s inflammatory process, particularly its resolution. Its expression on macrophages is often upregulated when these cells switch to an “alternatively activated” or M2 phenotype, contrasting with the pro-inflammatory M1 macrophage type.
CD163 contributes to inflammation resolution by scavenging pro-inflammatory and oxidative hemoglobin, producing anti-inflammatory heme metabolites. CD163-expressing macrophages are present at sites of inflammation, such as chronically inflamed arthritis joints and atherosclerotic plaques. They also help control inflammation by removing components of damaged cells.
CD163 as a Disease Biomarker
Soluble CD163 (sCD163), a form of the protein shed from cell surfaces, circulates in the blood and serves as an indicator of macrophage activation. Elevated sCD163 levels are observed in a broad range of acute and chronic inflammatory disorders. It serves as a useful prognostic marker in various health conditions.
In chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, increased sCD163 levels often reflect heightened macrophage activity and disease severity. For example, in systemic sclerosis, elevated serum sCD163 levels are associated with increased pulmonary artery systolic pressure and digital ulceration, suggesting macrophage involvement in disease development. In cardiovascular diseases, particularly atherosclerosis, higher levels of CD163-positive macrophages in plaques correlate with disease progression and an increased risk of events like myocardial infarction.
CD163 also holds relevance in certain cancers, where high levels of CD163-positive tumor-associated macrophages (TAMs) are linked to tumor progression and worse prognosis in types like breast and rectal cancer. In infections like HIV, elevated sCD163 levels are associated with increased inflammation and can predict cardiovascular disease burden. sCD163 has also been identified as an important prognostic marker in conditions such as liver failure and hemophagocytic lymphohistiocytosis.
Measuring CD163 Levels
CD163 levels are commonly measured in clinical and research settings to assess macrophage activity. The soluble form, sCD163, is analyzed in blood samples, specifically serum or plasma. This is often done using an enzyme-linked immunosorbent assay (ELISA), a laboratory technique that detects and quantifies specific proteins.
While sCD163 in blood is a primary measurement, CD163 can also be detected directly on cell surfaces of monocytes and macrophages using flow cytometry, or in tissue samples through immunohistochemistry. Normal sCD163 levels in healthy individuals range from 0.5 to 2 µg/mL. Changes in these levels can indicate disease activity or a response to treatment. For instance, in kidney inflammation like glomerulonephritis, sCD163 can be measured in urine, providing information about inflammation severity and treatment effectiveness.