β2-microglobulin
Summary
β2-microglobulin is a small protein component of MHC class I molecules, found on the surface of all nucleated cells. It is filtered by the renal glomerulus and reabsorbed/catabolized by the proximal tubule, making serum levels useful as a marker of GFR and tubular function. It's also elevated in certain malignancies, notably multiple myeloma, where it serves as a prognostic marker.
Detail
β2-microglobulin (β2M) is a non-glycosylated protein that forms the invariant light chain of MHC class I molecules, pairing non-covalently with the heavy chain alpha subunit on the surface of all nucleated cells (not expressed on RBCs). It is essential for proper folding and surface expression of MHC I, which presents endogenous peptides to CD8+ cytotoxic T cells.
Clinically, β2M is freely filtered by the glomerulus due to its small size (~11.8 kDa) and is almost completely reabsorbed and catabolized by proximal tubular cells. This makes elevated urinary β2M a marker of proximal tubular dysfunction (e.g., in Fanconi syndrome, heavy metal toxicity like cadmium poisoning, or drug-induced tubulopathy), while elevated serum β2M indicates decreased glomerular filtration rate (renal insufficiency) or increased cellular turnover/production.
In oncology, serum β2M is a significant prognostic biomarker in multiple myeloma, where it reflects tumor burden and renal function; it is incorporated into the International Staging System (ISS) for myeloma—higher levels correlate with worse prognosis. It is also elevated in other lymphoproliferative disorders (e.g., CLL, lymphoma) and conditions with increased cell turnover.
Additionally, β2M is the protein that forms amyloid deposits in dialysis-related amyloidosis, a complication of long-term hemodialysis where β2M accumulates because conventional dialysis membranes do not effectively clear it, leading to deposition in joints and other tissues (carpal tunnel syndrome, arthropathy).
Key associations for boards: MHC class I component, marker of GFR, multiple myeloma prognostic marker (part of ISS staging), dialysis-related amyloidosis, and proximal tubular dysfunction marker.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- Kumar & Clark's Clinical Medicine
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