Globulin
Group of proteins including antibodies
18 of 22 providers
Liver Function
autoimmune conditions
What is Globulin?
Globulins are a diverse group of proteins in your blood that serve multiple vital functions, primarily related to immune system function and substance transport. They account for about 40-45% of total plasma protein. Globulins are typically calculated as Total Protein minus Albumin, though they can also be measured by serum protein electrophoresis (SPEP) which separates them into subfractions.
Globulins consist of several types:alpha-1 and alpha-2 globulins (transport proteins and acute phase reactants), beta globulins (including transferrin for iron transport and complement proteins for immunity), and gamma globulins (immunoglobulins or antibodies produced by plasma cells). The albumin/globulin (A/G) ratio is clinically useful—a low ratio suggests immune activation, chronic infection, or liver disease.
Elevated globulins typically indicate immune system activation from chronic infections, autoimmune diseases, or production of abnormal proteins (like in multiple myeloma). Low globulins suggest immune deficiency or protein loss. Unlike albumin which reflects liver synthesis and nutrition, globulins primarily reflect immune system activity and inflammatory status.
Why Globulin Reveals Your Immune and Inflammatory Status
- Immune function indicator:Gamma globulins (antibodies) reflect immune system capacity. Low levels indicate immunodeficiency;high levels suggest chronic infection or autoimmune disease
- Chronic disease detection:Elevated globulins are seen in chronic infections (TB, HIV, hepatitis), autoimmune conditions (lupus, RA), and malignancies (multiple myeloma, lymphoma)
- A/G ratio significance:Low A/G ratio (<1.0) suggests chronic inflammation, liver disease, or protein-losing conditions. High ratio (>2.5) may indicate immunodeficiency
- Monoclonal protein screening:Markedly elevated globulins (>5 g/dL) warrant investigation for multiple myeloma or other plasma cell disorders
- Inflammation marker:Globulins increase as acute-phase reactants during inflammation, complementing CRP and ESR
- Protein loss detection:Low globulins with low albumin indicate protein-losing enteropathy or nephrotic syndrome
Optimal vs Standard Ranges
Optimal2.0-3.5 g/dL▼
- Normal immune function with balanced inflammatory status
- A/G ratio of 1.2-2.2 is optimal, indicating appropriate balance between liver protein synthesis (albumin) and immune proteins (globulins)
- Reflects absence of chronic infection, autoimmune disease, or significant inflammation
Borderline High3.5-4.5 g/dL▼
- Suggests mild immune activation or chronic inflammation
- Common in chronic infections, mild autoimmune conditions, or chronic inflammatory states
- Check A/G ratio—if <1.0, investigate further
- Consider CRP, ESR, and SPEP
- If isolated finding without symptoms, may reflect individual variation
- Retest in 3-6 months
Low (Hypoglobulinemia)<2.0 g/dL▼
- Indicates immunodeficiency, protein loss, or liver synthesis dysfunction
- Check immunoglobulin levels (IgG, IgA, IgM) to assess immune function
- Evaluate for primary immunodeficiency (genetic), secondary immunodeficiency (HIV, medications), protein-losing enteropathy, or nephrotic syndrome
- If low albumin also present, suggests severe protein loss or malnutrition
High (Hyperglobulinemia)>4.5 g/dL▼
- Indicates significant immune activation or pathological protein production
- A/G ratio typically <1.0
- Requires investigation with SPEP to differentiate polyclonal (multiple types) from monoclonal (single type) elevation
- Polyclonal:Chronic infections (hepatitis, TB, HIV), autoimmune diseases (lupus, RA, Sjögren's), chronic liver disease
- Monoclonal (>5 g/dL):Multiple myeloma, lymphoma, chronic lymphocytic leukemia
- Urgent hematology referral if monoclonal spike present
Scientific Evidence
Albumin/Globulin Ratio in Liver Disease
In chronic liver disease, the A/G ratio progressively decreases as cirrhosis advances. Albumin synthesis declines while globulins increase due to chronic immune activation. A/G ratio <1.0 is commonly seen in cirrhosis and correlates with disease severity. The ratio helps distinguish cirrhosis from other causes of low albumin.
Hyperglobulinemia as Clue to Multiple Myeloma
Multiple myeloma typically presents with markedly elevated globulins (>5 g/dL) and A/G ratio <1.0 due to monoclonal immunoglobulin production by malignant plasma cells. SPEP reveals a characteristic monoclonal spike. Early detection through recognition of elevated globulins and appropriate workup improves outcomes, as treatment is most effective when started before significant organ damage.
MGUS Prevalence and Progression
Monoclonal gammopathy of undetermined significance (MGUS) affects 3-5% of people over age 50 and ~8% over age 70. Most cases are benign, but MGUS progresses to multiple myeloma at a rate of ~1% per year. Monitoring includes serial SPEP, free light chains, and clinical assessment. Higher risk features include elevated free light chain ratio and monoclonal protein >1.5 g/dL.
Source:Kyle RA, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362-1369.
Hypoglobulinemia and Infection Risk
Patients with IgG <400 mg/dL have significantly increased risk of recurrent bacterial infections, particularly encapsulated organisms (pneumococcus, H. influenzae). Immunoglobulin replacement therapy (IVIG or SCIG) reduces infection rates by 60-80% in patients with primary or secondary immunodeficiency causing hypoglobulinemia.
Source:Bonilla FA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.
Globulins in Autoimmune Disease
Polyclonal hyperglobulinemia is common in autoimmune diseases, reflecting widespread B-cell activation and antibody production. In SLE, elevated globulins (3.5-5.5 g/dL) with low A/G ratio (<1.0) are typical. Globulin levels correlate with disease activity—decreasing with successful treatment and increasing during flares. Serial monitoring aids in disease management.
Source:Arbuckle MR, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
Which Providers Test Globulin?
Full Provider Comparison
| Provider | Includes | Annual Cost | Biomarkers |
|---|---|---|---|
 Superpower | ✓ | $199 | 100+ (150 with ratios) |
 WHOOP Advanced Labs | ✓ | $349 | 65 |
 Labcorp OnDemand | — | $398 | 30+ |
| ✓ | $486 | 40+ | |
| — | $444 | 288 | |
| ✓ | $349 | 100+ | |
| — | $761 | 54 | |
 Function Health | ✓ | $365 | 160+ |
| ✓ | $250 | 65 | |
| ✓ | $495 | 70+ | |
| ✓ | $895 | 100+ | |
| ✓ | $1950 | 150+ | |
| ✓ | $375 | 80+ | |
| — | $Varies | 75+ | |
| ✓ | $190 | 100+ | |
| ✓ | $99 | 50 | |
| ✓ | $124 | 60 | |
| ✓ | $199 | 50 | |
| ✓ | $499 | 120+ | |
| ✓ | $4188 | 70-80+ | |
| ✓ | $375 | 85 | |
| ✓ | $700 | 128 |
Frequently Asked Questions
What is Globulin?
Group of proteins including antibodies
What is the optimal range for Globulin?
The standard reference range for Globulin is autoimmune conditions. Optimal ranges may differ based on individual health goals and expert recommendations.
Which blood test providers include Globulin?
18 out of 22 blood testing providers include Globulin in their panels. This biomarker is widely available across major providers.
What category does Globulin fall under?
Globulin is categorized under Liver Function. This category includes biomarkers that help assess related aspects of health and wellness.
Medical Disclaimer
This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider about your specific health needs.
Last reviewed:2026-02-20