What causes low Secretory Immunoglobulin A (SIGA) levels in stool?

Causes of Low Secretory Immunoglobulin A (SIgA) in Stool

Low secretory IgA (SIgA) levels in stool are most commonly caused by selective IgA deficiency (SIGAD), medication side effects, or as an early manifestation of other immunodeficiency disorders.

Primary Causes

Selective IgA Deficiency (SIGAD)

• SIGAD is defined as serum IgA level <7 mg/dL with normal IgG and IgM levels in patients older than 4 years 1
• Most common primary immunodeficiency, affecting approximately 1 in 300-700 white individuals in the United States 1
• Patients with SIGAD typically have low or absent SIgA in stool, saliva, and other mucosal secretions 2
• Approximately 20-25% of cases have a family history of either SIGAD or Common Variable Immunodeficiency (CVID) 1

Partial IgA Deficiency

• Patients with serum IgA levels >7 mg/dL but below normal range also show reduced SIgA levels in stool and other secretions 2
• These patients should not be diagnosed with SIGAD but may still have clinical manifestations 1

Secondary Causes

Medication-Induced IgA Deficiency

• Several medications can cause reversible IgA deficiency with subsequent low SIgA in stool 1:
  • Antiepileptics (phenytoin, carbamazepine, valproic acid, zonisamide)
  • Anti-inflammatory drugs (sulfasalazine, NSAIDs)
  • Immunomodulators (gold, penicillamine, hydroxychloroquine)
  • Antibiotics (through disruption of microbiome) 3

Early Manifestation of Other Immunodeficiencies

• Low SIgA in stool may be an early sign of Common Variable Immunodeficiency (CVID) 1
• Some patients with SIGAD progress to CVID later in life 1
• IgG subclass deficiencies may co-exist with low SIgA 1

Gastrointestinal Disorders

• Celiac disease is associated with selective IgA deficiency and can present with low SIgA in stool 1, 4
• Inflammatory bowel conditions may affect mucosal immunity and SIgA production 5, 6

Clinical Implications of Low SIgA in Stool

Increased Susceptibility to Infections

• Gastrointestinal infections, particularly with Giardia lamblia 3, 6
• Increased risk of respiratory and sinopulmonary infections 1
• Impaired specific antibody responses, particularly to pneumococcal polysaccharide 1

Autoimmune Associations

• Increased risk of autoimmune diseases including celiac disease, thyroid disorders, and type 1 diabetes 1, 3
• Recent research shows that mucosal IgA deficiency leads to aberrant systemic exposures to commensal microbes, increasing likelihood of immune dysregulation 7

Diagnostic Considerations

• Measurement of total serum IgA is essential when evaluating low SIgA in stool 1
• Fecal SIgA levels correlate with salivary SIgA levels but not with urinary SIgA levels 2
• Consider testing for celiac disease, as it's commonly associated with IgA deficiency 1, 4

Management Approach

• Investigate medication use that could cause reversible IgA deficiency 1
• Monitor patients with confirmed low SIgA for complications including infections and autoimmune conditions 1
• Consider aggressive antimicrobial therapy or prophylaxis for patients with recurrent infections 1
• Treat atopic disease aggressively if present 1
• In rare cases with significant clinical impact, IgG replacement therapy may be considered 1

Pitfalls to Avoid

• Don't diagnose SIGAD in patients with IgA levels >7 mg/dL 1
• Be aware that standard serological tests for celiac disease may be falsely negative in IgA deficiency 1
• Consider that low SIgA may be an early sign of developing CVID, requiring long-term monitoring 1