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Beta 2‐microglobulin (β2‐M)
(β2-Microglobulin – Low-Molecular-Weight Protein – Renal & Hematologic Marker)
Synonyms
- β2-Microglobulin
- B2M
- β2-M
- Beta-2-microglobulin
- Light chain–related protein
- Class I MHC light chain component
Units of Measurement
nmol/L, mg/L, mg/dL, mg/100mL, mg%, µg/mL, ng/mL, µg/L
Description
Beta-2 microglobulin is a 11.8 kDa low-molecular-weight protein that forms the light chain of MHC class I molecules, found on almost all nucleated cells.
Key features:
- Produced at a constant rate by all cells
- Freely filtered by glomerulus
- Almost completely absorbed & catabolized in proximal tubule
Thus, β2-microglobulin is a sensitive biomarker for:
- Renal tubular function
- Glomerular filtration
- Hematologic malignancies (MM, lymphoma)
- Inflammatory and immune activation states
Physiological Role
- Component of MHC class I → antigen presentation
- Present on lymphocytes, platelets, most nucleated cells
- Normal serum levels reflect balance between production & renal clearance
Clinical Significance
Elevated β2-Microglobulin
1. Kidney Disease
- Glomerular dysfunction → decreased filtration
- Tubular dysfunction → reduced reabsorption
- Acute & chronic kidney disease
- Nephrotoxic drug injury
Higher β2-M = worse renal function.
2. Hematologic Malignancies
Very important prognostic marker in:
- Multiple Myeloma (MM) - incorporated in ISS staging
- Lymphoma
- CLL
- Waldenström macroglobulinemia
High β2-M → high tumor burden & poor prognosis.
3. Immune Activation
Mild–moderate elevation in:
- Autoimmune diseases
- Chronic infections (HIV, HCV)
- Inflammatory states
4. Transplant Rejection
- Elevated β2-M in acute rejection
- Used in follow-up of renal transplant patients
Low β2-Microglobulin
Not clinically significant.
May occur in:
- Severe immunodeficiency
- Genetic MHC class I defects (rare)
Reference Intervals
(Tietz 8E + Mayo + ARUP + KDIGO renal references)
Serum β2-Microglobulin
- 0.7 – 1.8 mg/L
- ≈ 60 – 150 nmol/L
Urine β2-Microglobulin
- < 0.3 mg/L (random)
- < 0.3 mg/g creatinine
Multiple Myeloma Prognostic Staging (ISS)
- Stage I: β2-M < 3.5 mg/L
- Stage II: 3.5–5.5 mg/L
- Stage III: > 5.5 mg/L (worst prognosis)
Unit Meanings
| Unit | Meaning |
| nmol/L | nanomole per liter |
| mg/L | milligram per liter |
| mg/dL / mg% | milligram per deciliter |
| mg/100 mL | mg% |
| µg/mL | microgram per milliliter |
| µg/L | microgram per liter |
| ng/mL | nanogram per milliliter |
Diagnostic Uses
1. Kidney Function Evaluation
- Glomerular filtration: β2-M rises early in GFR decline
- Tubular damage marker: urinary β2-M sensitive for proximal tubulopathy
Useful in: - AKI
- CKD
- Drug nephrotoxicity (cisplatin, aminoglycosides)
- Fanconi syndrome
2. Multiple Myeloma & Lymphoma
β2-M is a central prognostic marker:
- Correlates with tumor burden
- Independent risk factor
- Used in ISS staging
3. Chronic Infections
Higher in HIV, HCV, TB → reflects immune activation.
4. Autoimmune Disorders
Raised in:
- Rheumatoid arthritis
- SLE
- Sjögren syndrome
5. Transplant Medicine
Monitoring for:
- Acute kidney rejection
- Chronic graft dysfunction
Analytical Notes
- Measured by immunoassay (chemiluminescence/nephelometry)
- Hemolysis minimally affects results
- Freeze if storage > 48 hours
- Urine sample must be fresh; β2-M degrades in acidic urine (pH < 6)
- Avoid contamination with monoclonal proteins in MM — interpret with clinical context
Clinical Pearls
- β2-microglobulin rises earlier than creatinine in some kidney injuries.
- Strongest biochemical predictor of prognosis in multiple myeloma.
- Persistent elevation with normal creatinine → consider lymphoma or chronic infection.
- β2-M is filtered by glomeruli and reabsorbed by tubules → useful to differentiate glomerular vs tubular disease.
- In CKD, β2-M may accumulate and contribute to dialysis-related amyloidosis.
Interesting Fact
β2-microglobulin is so small (<12 kDa) that it was once proposed as the ideal endogenous GFR marker, but its strong tubular handling prevents its use as a pure filtration marker.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Renal Biomarkers.
- KDIGO Kidney Evaluation Guidelines.
- IFCC Reference Procedures - Low-MW Proteins.
- Mayo Clinic Laboratories - β2-Microglobulin.
- ARUP Consult - Myeloma & Kidney Marker Guidance.
- NIH / MedlinePlus - β2-Microglobulin.
- Hematology Oncology Texts - Myeloma Staging & Prognosis.