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

Causes of Low Secretory Immunoglobulin A (SIgA) in Stool

Low secretory IgA (SIgA) in stool is primarily caused by Selective IgA Deficiency (SIGAD), medication effects, or as an early manifestation of other immunodeficiencies, with significant implications for gastrointestinal health and immune function. 1

Primary Causes

• Selective IgA Deficiency (SIGAD): Defined as serum IgA level <7 mg/dL with normal IgG and IgM levels in patients older than 4 years, this is the most common primary immunodeficiency affecting approximately 1 in 300-700 white individuals in the United States 1, 2
• Genetic factors: 20-25% of SIGAD patients have a family history of either SIGAD or Common Variable Immunodeficiency (CVID), suggesting genetic predisposition 2
• Defective B cell differentiation: SIGAD results from impaired terminal lymphocyte differentiation leading to underproduction of serum and mucosal IgA despite normal IgA genes 3

Secondary/Acquired Causes

• Medication-induced: Several medications can cause reversible IgA deficiency with subsequent low SIgA in stool 1:

  • Antiepileptics (phenytoin, carbamazepine, valproic acid, zonisamide) 2
  • Anti-inflammatory drugs (NSAIDs, sulfasalazine) 2
  • Immunomodulators (hydroxychloroquine, gold, penicillamine) 2
  • Antibiotics (can disrupt microbiome which influences IgA levels) 4

• Early manifestation of other immunodeficiencies:

  • Common Variable Immunodeficiency (CVID) - some patients with SIGAD develop CVID later in life 2, 1
  • IgG subclass deficiencies 1
  • Good syndrome (thymoma with immunodeficiency) 2

• Gastrointestinal disorders:

  • Celiac disease - strongly associated with IgA deficiency 1, 3
  • Inflammatory bowel conditions 5
  • Chronic infections, particularly with Giardia lamblia 1, 4

• Gut dysbiosis: Patients with low SIgA demonstrate gut microbiome imbalances with enriched proinflammatory bacterial phyla 5

Clinical Implications

• Increased infection risk: Patients with low SIgA in stool have higher rates of:

  • Gastrointestinal infections, particularly with Giardia lamblia 1, 4
  • Respiratory tract infections 4
  • Viral gastrointestinal infections - patients with low serum and secretory IgA show increased prevalence of GI viruses 6

• Autoimmune disease associations:

  • Celiac disease (most common association) 3
  • Thyroid disorders 1, 4
  • Type 1 diabetes 1, 4
  • Systemic lupus erythematosus 4

• Mucosal inflammation: Virus-positive patients with antibody deficiencies show signs of mucosal inflammation with elevated fecal calprotectin levels 6

Diagnostic Approach

1. Measure total serum IgA to determine if SIGAD is present (defined as <7 mg/dL) 1, 2
2. Investigate medication history to identify potential reversible causes 2
3. Screen for celiac disease using IgG-based tests if IgA deficiency is confirmed (standard IgA-based tests will be falsely negative) 2, 1
4. Evaluate for other immunodeficiencies if clinically indicated, particularly if recurrent infections are present 1
5. Consider stool testing for pathogens, particularly Giardia lamblia 4

Management Considerations

• Address reversible causes: Discontinue medications that may cause IgA deficiency if clinically appropriate 2
• Infection management: Consider aggressive antimicrobial therapy or prophylaxis for patients with recurrent infections 2
• Monitor for complications: Regular follow-up for patients with confirmed low SIgA to detect infections, autoimmune conditions, and malignancy 2, 1
• Treat associated conditions: Aggressively manage atopic disease if present 2
• Blood transfusion precautions: Some IgA-deficient individuals have anti-IgA antibodies that can cause severe transfusion reactions (though rare) 3