What is the mechanism of type III hypersensitivity, which is characteristic of Systemic Lupus Erythematosus (SLE)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: November 8, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Type III Hypersensitivity in Systemic Lupus Erythematosus

Type III hypersensitivity is the result of antibodies binding with antigens, forming immune complexes that move through the circulation and deposit in tissues, triggering complement activation and inflammatory damage.

Mechanism of Type III Hypersensitivity

Type III hypersensitivity is fundamentally an immune complex-mediated process that characterizes SLE 1, 2. The mechanism involves:

  • Antibody-antigen complex formation: Antibodies (particularly against nuclear antigens like double-stranded DNA) bind with their target antigens to form circulating immune complexes 2, 3

  • Immune complex deposition: These complexes circulate through the bloodstream and deposit in various tissues, particularly in blood vessel walls, kidneys, joints, and skin 2, 3

  • Complement system activation: Local deposition of these immune complexes activates the complement system, leading to serious inflammatory conditions 2

  • Tissue inflammation and damage: The complement activation recruits inflammatory cells and mediators, causing tissue injury at the sites of immune complex deposition 2, 4

Why SLE is a Prototype Type III Hypersensitivity

SLE exemplifies Type III hypersensitivity because 2:

  • Autoantibody production: Patients characteristically produce autoantibodies against double-stranded DNA, histones, nucleosomes, and other chromatin components 2, 3

  • Immune complex disease: The formation and deposition of anti-nuclear antibodies complexed with released chromatin drives the pathology 2

  • Multi-organ involvement: The circulating nature of immune complexes explains why SLE affects multiple organ systems including skin (facial rash), joints (arthritis), kidneys (lupus nephritis), and blood vessels 5, 3

Distinguishing Type III from Other Hypersensitivity Types

The correct answer eliminates the other options 1:

  • Not Type I: Type I hypersensitivity is IgE-mediated with mast cell degranulation causing immediate reactions like anaphylaxis and histamine release—this is not the mechanism in SLE 6, 1

  • Not Type II: Type II involves antibodies directly attacking cell surface antigens causing cytotoxic reactions (like hemolytic anemia as an isolated phenomenon), rather than circulating immune complex deposition 1

  • Not Type IV: Type IV is T-cell mediated (delayed-type hypersensitivity) seen in tuberculosis and contact dermatitis, not antibody-mediated like SLE 1

Clinical Relevance to This Patient

For RO's presentation 5, 3:

  • The joint pain reflects immune complex deposition in synovial tissues causing inflammatory arthritis
  • The facial rash results from immune complex deposition in dermal blood vessels and skin structures
  • Both manifestations stem from the same Type III hypersensitivity mechanism: circulating immune complexes depositing in target tissues and triggering local complement-mediated inflammation

References

Guideline

Hipersensibilidade e Falha de Tolerância Imunológica

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Systemic lupus erythematosus.

Lancet (London, England), 2024

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.