Unit Converter
Immunoglobulin M (IgM)
Synonyms
- IgM
- Serum IgM
- Macroglobulin
- µ-heavy chain immunoglobulin
- First-line antibody
Units of Measurement
- mmol/L
- µmol/L
- g/L
- mg/dL
- mg/100 mL
- mg%
- mg/mL
Molecular Weight
Pentameric IgM: ~900 kDa
Key Conversions
Using MW ≈ 900,000 g/mol:
1 g/L ≈ 0.00111 mmol/L
1 mmol/L ≈ 900 g/L
1 g/L ≈ 1.11 µmol/L
1 mg/dL = 0.01 g/L
mg% = mg/dL = mg/100 mL
1 mg/mL = 1 g/dL = 10 g/L
Description
Immunoglobulin M (IgM) is the largest immunoglobulin and the first antibody produced during:
- Primary immune responses
- Acute infections
- Early-stage humoral immunity
Structure:
- Pentameric (five IgM units + J-chain)
- High avidity despite lower affinity
IgM is produced by B cells early in immune activation and is the major antibody in the primary (initial) immune response.
Physiological Role
1. First Line of Defense
- Rapidly produced during acute infection
- Major responder before class-switching to IgG/IgA occurs
2. Complement Activation
- IgM is the most potent activator of the classical complement pathway
- 1 molecule of IgM can activate complement (vs 2 IgG molecules)
3. Natural Antibodies
Produced without antigen exposure:
- ABO blood group isohemagglutinins (IgM anti-A, anti-B)
- Early anti-bacterial antibodies
4. Agglutination
IgM efficiently agglutinates:
- Bacteria
- Viruses
- Erythrocytes
Clinical Significance
High IgM (Hyper-IgM)
1. Acute Infection
IgM rises rapidly in:
- Viral infections (hepatitis A/B/C, CMV, EBV)
- Bacterial infections
- Parasitic infections
Used in “IgM-specific serology” for:
- Dengue IgM
- HAV IgM
- HBc IgM
- CMV IgM
- Toxoplasma IgM
2. Autoimmune Disorders
- Rheumatoid factor (RF) is an IgM antibody to IgG
- Elevated IgM in autoimmune hepatitis
3. Liver Diseases
- Primary biliary cholangitis (PBC): selective IgM elevation
- Chronic liver disease
4. Waldenström Macroglobulinemia
Monoclonal IgM > 30–40 g/L →
- Hyperviscosity
- Anemia
- Neuropathy
5. Hyper-IgM Syndromes (Genetic)
Defects in CD40/CD40L →
- High IgM
- Very low IgG/IgA
- Severe infections
Low IgM (Hypogammaglobulinemia)
Very important clinically.
1. Common Variable Immunodeficiency (CVID)
Low IgM ± low IgA/IgG.
2. Selective IgM Deficiency
Defined as:
- Isolated low IgM (<0.2 g/L)
Often presents with: - Recurrent sinopulmonary infections
- Allergies
- Autoimmunity
3. X-Linked Agammaglobulinemia (XLA)
Very low IgM with absent B cells.
4. Secondary Causes
- Nephrotic syndrome
- Protein-losing enteropathy
- Severe malnutrition
- Chemotherapy
- Rituximab therapy
- Leukemia/lymphoma
5. Infancy (<6 months)
Immature B-cell immunity → physiologic low IgM.
Reference Intervals
Adults
- 0.4 – 2.3 g/L
(= 40 – 230 mg/dL)
Children
| Age | IgM (mg/dL) |
| 0–1 month | 5 – 25 |
| 1–12 months | 20 – 100 |
| 1–3 years | 30 – 140 |
| 3–6 years | 40 – 160 |
| 6–12 years | 50 – 200 |
| >12 years | Adult range |
Critical Patterns
- Isolated IgM < 0.2 g/L → consider selective IgM deficiency
- IgM > 30–40 g/L → Waldenström macroglobulinemia
Diagnostic Uses
1. Infection Serology
Detection of acute infection by IgM-specific antibodies (“IgM ELISA”).
2. Evaluation of Primary Immunodeficiency
- CVID
- Selective IgM deficiency
- XLA
- Hyper-IgM syndromes
3. Screening for Waldenström Macroglobulinemia
High IgM + symptoms → SPEP/UPEP + bone marrow.
4. Autoimmune Disease Workup
IgM-rheumatoid factor elevated in RA.
5. Liver Disease Evaluation
Selective IgM high in Primary biliary cholangitis (PBC).
6. Vaccine Response Assessment
IgM rises early → indicates primary response.
Analytical Notes
- Measured by nephelometry/turbidimetry
- Serum preferred
- Very high IgM can cause hyperviscosity → sample handling issues
- In macroglobulinemia, IgM precipitation may cause pseudohyponatremia
Clinical Pearls
- IgM is the first antibody to rise and first to fall after an infection.
- Low IgM with normal IgG/IgA suggests selective IgM deficiency.
- IgM is the only antibody produced by the fetus (high fetal IgM → congenital infection).
- Waldenström macroglobulinemia causes extremely high IgM and hyperviscosity.
- In PBC, IgM elevation is characteristic and helps differentiate from autoimmune hepatitis (IgG elevation).
Interesting Fact
IgM is so large (pentameric) that it cannot cross the placenta, making it extremely useful in identifying in utero infections (elevated newborn IgM = congenital infection).
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Immunoglobulins.
- ESID/AAAAI Guidelines - Primary Immunodeficiency.
- Mayo Clinic Laboratories - IgM.
- ARUP Consult - Immunoglobulin Testing.
- NIH / MedlinePlus - Immunoglobulins.