Pathology · Immunopathology (Hypersensitivity, Autoimmunity, Immunodeficiency, Amyloidosis)

In systemic light chain (AL) amyloidosis, the amyloid fibrils are derived from immunoglobulin light chains. Kappa or lambda light chains can form fibrils, but lambda chains are overrepresented. The serum/urine biomarker most specific for monitoring AL amyloidosis treatment response is:

  • A Serum amyloid P (SAP) component levels
  • B Total serum immunoglobulin (IgG/IgA/IgM) concentration
  • C Free light chain (FLC) difference (dFLC) — difference between involved and uninvolved light chains
  • D Urine Bence-Jones protein by electrophoresis
Correct answer: C. Free light chain (FLC) difference (dFLC) — difference between involved and uninvolved light chains

Explanation

In AL amyloidosis, the amyloidogenic free light chain (lambda > kappa at 3:1 ratio) is produced by a clonal plasma cell population. The 'dFLC' (difference in free light chain = involved FLC minus uninvolved FLC) is the validated haematological response biomarker: a >50% reduction in dFLC indicates haematological response and correlates with organ response and survival. Serum free light chain assay (nephelometry) replaced older urine Bence-Jones protein testing (low sensitivity, requires 24-hour urine). SAP scintigraphy tracks amyloid organ burden but is not a routine treatment monitoring tool. Total immunoglobulin levels are less specific as they include polyclonal and other paraproteins. dFLC is included in the Consensus Response Criteria for AL amyloidosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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