In a patient with bronchiectasis, when should serum immunoglobulin quantification be performed and when is immunoglobulin replacement therapy indicated?

Serum Immunoglobulin Testing in Bronchiectasis

Serum immunoglobulin quantification (IgG, IgA, and IgM) should be performed in ALL patients with bronchiectasis as part of the initial diagnostic evaluation, regardless of clinical presentation. 1

When to Perform Serum Immunoglobulin Testing

Universal Screening Recommendation

• Measure serum IgG, IgA, and IgM in every patient diagnosed with bronchiectasis as part of the standard diagnostic panel to identify treatable underlying causes. 1
• This testing is low-cost, readily available, and identifies antibody deficiency syndromes in 7% (range 2-17%) of bronchiectasis patients—a significant proportion with directly modifiable disease. 1
• The 2019 British Thoracic Society guidelines explicitly state this as a Grade C recommendation, meaning it should be standard practice. 1

Additional Functional Testing

• Consider measuring baseline pneumococcal-specific antibody levels against capsular polysaccharides in all patients to detect specific antibody deficiency, even when total immunoglobulin levels appear normal. 1
• If pneumococcal antibodies are low, administer the 23-valent polysaccharide pneumococcal vaccine and remeasure specific antibody levels 4-8 weeks later to assess functional antibody production. 1
• This functional testing is critical because 17.5% of bronchiectasis patients have specific antibody deficiency (SAD) despite normal serum immunoglobulin and IgG subclass levels. 2

IgG Subclass Testing

• Measure IgG subclasses when recurrent infections persist despite apparently adequate total IgG levels, as IgG subclass deficiency occurs in 5-7.5% of bronchiectasis patients. 3, 2

When Immunoglobulin Replacement Therapy is Indicated

Primary Indications (Strong Evidence)

Immunoglobulin replacement therapy is indicated when:

1. Primary hypogammaglobulinemia is documented:

   • IgG level typically <5 g/L (500 mg/dL) with IgA <0.1 g/L in primary immunodeficiency disorders. 1
   • Common variable immunodeficiency (CVID) accounts for 3% of adult bronchiectasis cases and requires lifelong replacement therapy. 1
   • Antibody deficiency can be confirmed by demonstrating decreased antibody production to two or more vaccines (tetanus, diphtheria, measles, mumps, pneumococcal). 1

2. Recurrent bacterial infections occur despite normal or borderline immunoglobulin levels:

   • At least 2-3 severe recurrent bacterial infections per year (pneumonia, sepsis, requiring hospitalization). 4
   • Documented culture-proven bacterial infections or failure of antibiotic therapy. 4
   • The presence of established bronchiectasis itself indicates prior irreversible lung damage and strengthens the indication for therapy. 5

3. IgG subclass deficiency with clinical significance:

   • Recurrent sinopulmonary infections with documented IgG subclass deficiency (particularly IgG2 or IgG3). 6
   • Poor antibody responses to polysaccharide antigens. 2
   • Evidence of progressive bronchiectasis or permanent organ damage. 4

Dosing and Target Levels

• Standard IVIG dosing: 0.4-0.5 g/kg every 3-4 weeks, adjusted based on clinical response rather than achieving a specific trough level. 1, 7, 8
• Target trough IgG levels vary widely between patients: 5-17 g/L (500-1700 mg/dL) to prevent breakthrough infections in CVID patients, with those having established bronchiectasis often requiring higher doses (0.2-1.2 g/kg/month). 7
• The primary endpoint is clinical response—specifically reduction in infection frequency and severity—not simply achieving a numerical IgG target. 5, 7

Evidence of Efficacy

• IVIG therapy in children with CVID reduced mean annual respiratory infections from 10.2 to 2.5 per patient, hospital stays from 1.36 to 0.21 per year, and antibiotic courses from 8.27 to 2.50 per patient. 8
• Early IVIG replacement therapy prevents development of bronchiectasis; in one study, 3 of 12 patients with pre-existing bronchiectasis showed resolution after initiating therapy. 8
• Patients with IgG deficiency benefit from IV immunoglobulin replacement, which is associated with reduced infection frequency and slowing of bronchiectasis progression. 1

Critical Clinical Pitfalls to Avoid

1. Do not wait for multiple severe infections before testing immunoglobulins—by that time, irreversible bronchiectasis may have already developed. 1

2. Do not assume normal total IgG excludes antibody deficiency—specific antibody deficiency to polysaccharide antigens occurs in 17.5% of patients with normal immunoglobulin levels. 2

3. Do not delay IVIG therapy in patients with documented primary immunodeficiency and bronchiectasis—the damage is progressive and early treatment prevents further deterioration. 1, 8

4. Do not use fixed IgG trough targets for all patients—individualize dosing based on infection frequency, with patients having bronchiectasis often requiring higher doses than those without structural lung disease. 7

5. Do not stop immunoglobulin replacement therapy in primary immunodeficiency disorders (such as CVID) even if target IgG levels are achieved—these patients require lifelong therapy. 5, 4