What is the clinical significance of CD163 (Cluster of Differentiation 163) in immune system disorders?

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Clinical Significance of CD163 in Immune System Disorders

CD163 is a scavenger receptor exclusively expressed on monocytes and macrophages that plays a crucial role in immune regulation, with its soluble form (sCD163) serving as a valuable biomarker for macrophage activation in various inflammatory disorders.

What is CD163?

  • CD163 is a hemoglobin scavenger receptor exclusively expressed on cells of the monocyte-macrophage lineage 1, 2
  • It functions primarily in the endocytosis of hemoglobin and hemoglobin/haptoglobin complexes 2
  • CD163 is particularly highly expressed in macrophages of the "alternative activation" phenotype that play a major role in dampening inflammatory responses 2
  • The extracellular domain of CD163 can be shed from the cell surface, creating soluble CD163 (sCD163) that circulates in blood 3

Regulation of CD163 Expression

  • CD163 expression is upregulated by anti-inflammatory mediators:
    • IL-10 and glucocorticoids strongly induce CD163 expression 1, 4
    • IL-6 (which has both pro- and anti-inflammatory effects) also upregulates CD163 1
  • CD163 expression is downregulated by pro-inflammatory mediators:
    • TNF-α and IFN-γ reduce CD163 expression 1, 4
  • Ectodomain shedding of CD163 (creating sCD163) is stimulated by:
    • Ligands of toll-like receptors 2,4, and 5 1
    • Various inflammatory stimuli 2

Diagnostic Value of sCD163

  • Normal sCD163 levels in healthy individuals range from 0.7-3.9 mg/L 3
  • Elevated sCD163 levels are observed in:
    • Chronic inflammatory conditions (atherosclerosis, asthma, rheumatoid arthritis) 5
    • Acute inflammatory conditions (sepsis, hepatitis, malaria) 5
    • Critically ill patients 1
    • Autoimmune hepatitis as an evolving biomarker 6
    • Macrophage activation syndrome 3
    • Liver diseases 3

Prognostic Value of sCD163

  • sCD163 serves as a general risk marker for:
    • Disease severity in inflammatory disorders 1, 5
    • Comorbidity and mortality in chronic inflammatory diseases 3
    • Predicting development of type 2 diabetes in both lean and obese subjects 3
    • Monitoring treatment response in inflammatory conditions 1

Role in Specific Immune System Disorders

  • In autoimmune hepatitis:

    • Soluble CD163 is an evolving biomarker that may guide future management 6
    • Can help distinguish autoimmune hepatitis from other liver diseases 6

  • In histiocytic disorders:

    • CD163 is a key immunophenotypic marker used to identify histiocytes in disorders like Erdheim-Chester disease (ECD) 6
    • In ECD, histiocytes show moderate to strong positive staining for CD163 (surface) 6
    • CD163 positivity helps differentiate ECD from Langerhans cell histiocytosis (LCH) 6

  • In chronic myelomonocytic leukemia (CMML):

    • Flow cytometry immunophenotyping may detect aberrancies in monocytic lineage markers including CD163 6

Therapeutic Implications

  • CD163 represents a potential target for:
    • Specifically delivering drugs to macrophages to enhance therapeutic efficiency 1
    • Minimizing adverse reactions in targeted therapies 1
    • Monitoring therapeutic response in inflammatory disorders 1

Clinical Applications in Practice

  • Measurement of sCD163 can be useful for:
    • Diagnosing and monitoring macrophage activation in inflammatory diseases 3
    • Assessing disease severity and prognosis in various inflammatory conditions 5
    • Therapeutic drug monitoring in inflammatory disorders 1
    • Risk stratification in chronic inflammatory diseases 3

Pitfalls and Considerations

  • sCD163 is not disease-specific but rather indicates macrophage activation 3
  • Interpretation of sCD163 levels should consider:
    • The patient's overall clinical picture 5
    • Presence of comorbidities that might affect macrophage activation 3
    • Medications that might influence CD163 expression (e.g., glucocorticoids) 1, 4

Future Directions

  • Further research is needed to:
    • Validate CD163/sCD163 as diagnostic and prognostic biomarkers in specific diseases 1
    • Explore the potential of CD163 as a therapeutic target 1
    • Better understand the biological functions of sCD163 in circulation 5

References

3
Research

Soluble CD163.

Scandinavian journal of clinical and laboratory investigation, 2012

4
Research

CD163 and its role in inflammation.

Folia histochemica et cytobiologica, 2011

6
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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