A 50-year-old woman with a long-standing history of rheumatoid arthritis presents with worsening joint pain, swelling, and progressive joint deformities. Which of the following types of hypersensitivity reaction is primarily responsible for the pathogenesis of this condition? (FMGE JAN 2026) A Type I hypersensitivity B Type II hypersensitivity C Type III hypersensitivity D Type IV hypersensitivity
C - Type III hypersensitivity
Rheumatoid arthritis (RA) is primarily a Type III (immune complex-mediated) hypersensitivity reaction. Here's the core mechanism:
- In RA, autoantibodies (most notably rheumatoid factor - IgM against the Fc portion of IgG, and anti-CCP antibodies) form immune complexes that deposit in synovial tissue and joints.
- These immune complexes activate the complement cascade (C3a, C5a), attracting neutrophils and macrophages into the synovium.
- Sustained inflammation leads to pannus formation - an invasive layer of activated synovial fibroblasts and inflammatory cells that erodes cartilage and bone, causing the progressive deformities seen in this patient.
Why the other options are wrong:
| Type | Mechanism | Classic Example |
|---|---|---|
| Type I | IgE-mediated, mast cell degranulation | Anaphylaxis, asthma, allergic rhinitis |
| Type II | Antibody-mediated cytotoxicity (IgG/IgM against cell surface) | Hemolytic anemia, Goodpasture's, myasthenia gravis |
| Type III | Immune complex deposition + complement activation | RA, SLE, serum sickness, post-strep GN |
| Type IV | T-cell mediated (delayed-type) | Contact dermatitis, TB reaction, graft rejection |
Important nuance: RA also has a significant Type IV component - CD4+ T cells (particularly Th17 cells) drive synovial inflammation and TNF-alpha/IL-1/IL-6 release (which is why anti-TNF biologics work). However, for the purpose of this FMGE question, the primary/classic classification is Type III, as immune complex deposition is the initiating mechanism emphasized in standard pathology teaching.
Answer: C - Type III hypersensitivity
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