Inflammation and Immune Pathology USMLE Step 1 Practice Question
A 68-year-old woman presents to rheumatology clinic with a 4-month history of symmetric polyarticular pain and swelling affecting her hands, wrists, and knees. She reports morning stiffness lasting approximately 2 hours that improves with activity. Physical examination reveals symmetric swelling and warmth of the PIP and MCP joints bilaterally, with preserved range of motion. Vital signs are normal with temperature 37.1°C. Laboratory studies show ESR 58 mm/hr, CRP 7.8 mg/dL, positive rheumatoid factor (titer 1:320), and positive anti-CCP antibodies. Ultrasound demonstrates synovial hypertrophy with power Doppler signals. A synovial biopsy specimen shows hyperplastic synovial tissue with prominent fibroblast-like synoviocytes, infiltrating inflammatory cells, and early cartilage erosion. Which of the following mechanisms best explains the progressive cartilage destruction seen in this patient?
Answer choices
- ADeposition of immune complexes in the synovial space leading to complement activation and cartilage matrix disruption without cellular invasion
- BProduction of matrix metalloproteinases by activated fibroblast-like synoviocytes that enzymatically degrade the cartilage extracellular matrixCorrect answer
- CDirect cytotoxic attack on chondrocytes by CD8+ T cells with subsequent apoptosis and loss of cartilage mass
- DRecruitment and activation of osteoclasts through RANKL-independent TNF-α signaling in the pannus tissue
- EType II hypersensitivity reaction against cartilage collagen epitopes with antibody-mediated complement fixation and chondrocyte lysis
- FProduction of IL-1 and TNF-α by synovial macrophages that stimulates chondrocyte apoptosis while preserving the cartilage matrix structure
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