What does it mean to have low IgG Subclass 4 levels?

Understanding Your Low IgG Subclass 4 Result

Your IgG4 level is below the detectable limit (<0.006 g/L), but this finding alone does not necessarily indicate a clinically significant problem—what matters most is whether you have recurrent infections that impact your quality of life. 1

What This Laboratory Result Means

Your lab results show:

• IgG1, IgG2, and IgG3 are all normal 1
• IgG4 is undetectable (below 0.006 g/L, with normal range 0.052-1.250 g/L) 1
• This represents an isolated IgG4 deficiency 2

Approximately 2.5% of healthy people naturally have levels below the normal range for at least one IgG subclass, so low levels don't automatically mean disease. 1

Clinical Significance: When to Worry

The key question is whether this laboratory finding matters for your health. You should be concerned if you experience: 1

• Recurrent sinopulmonary infections (frequent sinus infections, pneumonia, bronchitis), particularly with encapsulated bacteria 1
• Infections that negatively affect your quality of life despite aggressive antibiotic therapy 1
• Recurrent or chronic diarrhea 2
• Chronic respiratory symptoms (asthma, chronic cough) 2
• Evidence of end-organ damage such as bronchiectasis 1

If you are asymptomatic with no history of recurrent infections, no specific intervention is needed. 1

What IgG4 Does

IgG4 represents a small fraction of total IgG but has specific functions:

• IgG4 deficiency is the most common IgG subclass deficiency found in IgA-deficient patients (occurring in 26% of cases) 3
• It can occur as an isolated deficiency or combined with IgG2, IgA, or IgG1 deficiencies 2
• The biological role of IgG4 is still not completely clear—it may function differently than other IgG subclasses 4

Important Diagnostic Considerations

Age Matters

IgG4 deficiency should not be diagnosed in children younger than 10 years because IgG4 is present in very low concentrations in young children. 5 If you are under 10, this result may not be interpretable.

Confirm the Result

Abnormal IgG subclass levels should be confirmed with at least one additional measurement at least one month apart. 1, 5 A single low value may be transient.

Check for Secondary Causes

Certain medications can cause secondary IgG subclass deficiency, including: 1

• Antiepileptic drugs
• Gold compounds
• Penicillamine
• Hydroxychloroquine
• NSAIDs

Assess Functional Immunity

Laboratory values alone should not drive treatment decisions—you need functional testing: 1

• Measure specific antibody responses to protein vaccines (like tetanus toxoid) 1, 5
• Measure specific antibody responses to polysaccharide vaccines (like pneumococcal vaccine) 1, 5
• These tests determine if your immune system can actually produce protective antibodies despite the low IgG4 level

Next Steps Algorithm

If You Are Asymptomatic:

• No intervention needed 1
• Monitor for development of recurrent infections over time
• Be aware that some patients with IgG subclass deficiency may evolve into more severe immunodeficiency (like CVID) over time 1

If You Have Recurrent Infections:

1. Confirm IgG4 deficiency with repeat testing in at least one month 1, 5
2. Evaluate specific antibody responses to both protein and polysaccharide vaccines 1, 5
3. Assess for other immunodeficiencies (check IgA, IgM levels, lymphocyte subsets) 1
4. Review medication list for potential causative drugs 1

Treatment Considerations:

• Aggressive antimicrobial therapy and prophylaxis for recurrent infections 1
• Aggressive treatment of any atopic disease (asthma, allergies) 1
• IgG replacement therapy should NOT be initiated based solely on laboratory values without clinical correlation—it requires documented recurrent infections affecting quality of life, failure of antibiotic therapy, or impaired vaccine responses 1
• If IgG replacement is indicated, the standard dose is 400 mg/kg every 28 days 1

Critical Pitfalls to Avoid

Do not assume you need immunoglobulin replacement therapy just because of a low lab value. 1 Treatment decisions must be based on:

• Clinical symptoms (recurrent infections)
• Quality of life impact
• Failure of standard antibiotic therapy
• Impaired vaccine responses

Normal total IgG (which you have) does not exclude subclass deficiency, but conversely, isolated low subclass levels may not be clinically significant. 1