In multiple myeloma, the M-protein 'immunoparesis' (suppression of non-involved immunoglobulins) is caused primarily by which mechanism?

• A Direct consumption of immunoglobulins by amyloid fibrils in bone marrow
• B Hyperviscosity syndrome causing dilutional reduction of normal Ig
• C Suppression of normal B-cell differentiation by myeloma cell-derived DKK1 and APRIL cytokines ✓
• D Renal loss of immunoglobulins via Bence Jones proteinuria

Explanation

Myeloma plasma cells secrete DKK1 (Dickkopf-1) and a proliferation-inducing ligand (APRIL), among other cytokines, which suppress normal B-cell and plasma cell differentiation in the bone marrow, leading to immunoparesis. This is distinct from quantitative reduction by dilution or renal loss. Bence Jones proteinuria reflects free light chain excretion but does not account for suppression of IgG and IgA levels.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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