A 55-year-old woman with rheumatoid arthritis develops reactive (AA) amyloidosis. The amyloid A protein is derived from which serum precursor, and what is the pathological trigger for its overproduction?

• A Serum amyloid A (SAA) — an acute-phase reactant produced by hepatocytes under chronic IL-6 and IL-1 stimulation ✓
• B Transthyretin (TTR) — produced by liver and choroid plexus, undergoes conformational change under inflammatory conditions
• C Beta-2 microglobulin — shed from MHC class I molecules during chronic inflammation and dialysis
• D Apolipoprotein A-I — N-terminal fragment deposited under chronic hyperlipidaemia

Explanation

Reactive (secondary) amyloidosis (AA type) occurs as a complication of chronic inflammatory conditions: rheumatoid arthritis, bronchiectasis, osteomyelitis, inflammatory bowel disease, familial Mediterranean fever. The amyloid fibril precursor is serum amyloid A (SAA), an apolipoprotein associated with HDL. SAA is an acute-phase reactant synthesised in hepatocytes under stimulation by pro-inflammatory cytokines IL-1beta, IL-6, and TNF-alpha during sustained chronic inflammation. When SAA levels remain persistently elevated over years, partial proteolysis generates amyloid A (AA) fragments with beta-sheet conformation that deposit preferentially in kidneys (causing nephrotic syndrome), spleen, liver, and adrenals. TTR (transthyretin) amyloidosis (ATTR) is not AA type; beta-2-microglobulin amyloidosis is dialysis-associated; ApoA-I variants cause hereditary amyloidosis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.