What factors lower secretory IgA (Immunoglobulin A) levels in stool, particularly in a patient with a history of autoimmune disorders or recurrent infections?

Factors That Lower Secretory IgA in Stool

Common variable immunodeficiency (CVID) is the most important primary immunodeficiency that lowers secretory IgA, characterized by absent plasma cells in the intestinal lamina propria and recurrent infections. 1

Primary Immunodeficiencies

Selective IgA Deficiency

• Selective IgA deficiency (serum IgA <0.07 g/L after age 4 years with normal IgG and IgM) is the most common primary immunodeficiency and directly results in absent or severely reduced secretory IgA in stool 2, 3
• This represents a maturation defect in B cells preventing IgA production, though many patients remain asymptomatic due to compensatory secretory IgM 2
• Approximately 56-60% of pediatric patients with IgA deficiency develop clinical manifestations including recurrent respiratory infections (17.5%), recurrent pneumonia (6%), chronic diarrhea (6.5%), and celiac disease (6.6%) 4
• Some patients with IgA deficiency may evolve into more severe phenotypes like CVID over time 5, 4

Common Variable Immunodeficiency (CVID)

• CVID presents with low IgG (<5 g/L) plus low IgA or IgM, recurrent infections, and persistent diarrhea 1
• Histologically, CVID shows absence of plasma cells in the intestinal lamina propria, which are the primary producers of secretory IgA 1
• This represents a more severe defect than isolated IgA deficiency and requires immunoglobulin replacement therapy 1

Immunoglobulin Class-Switch Defects

• Deficiencies of activation-induced cytidine deaminase (AID) or uracil nucleoside glycosylase (UNG) result in severely reduced IgA with elevated IgM 1
• These patients have normal unswitched memory B cells but reduced class-switched memory B cells, preventing effective IgA production 1

Medications and Iatrogenic Causes

Immunosuppressive Therapies

• Corticosteroids at doses ≥20 mg prednisolone daily for ≥2 weeks suppress antibody production including secretory IgA 1
• Thiopurines (azathioprine, 6-mercaptopurine) impair B cell function and antibody responses 1
• Anti-TNF biologics (infliximab, adalimumab) reduce plasma cell populations and immunoglobulin production 1
• Vedolizumab (anti-α4β7 integrin) directly lowers stool SIgA levels after even a single dose by blocking B cell recruitment to intestinal lamina propria 6
• Etrolizumab (anti-β7 integrin) similarly compromises antibody-secreting cell migration to the gut 6

Other Medications

• Antiepileptic drugs, gold, penicillamine, hydroxychloroquine, and NSAIDs can cause secondary IgG subclass deficiencies that may extend to IgA 5

Intestinal Diseases

Inflammatory Bowel Disease

• IBD itself does not cause systemic immunodeficiency, but the dysregulated mucosal immune response can impair local IgA production 1, 6
• Loss of immune tolerance to bacterial antigens in IBD disrupts the normal B cell-IgA-microbiota interface 6
• Bacterial overgrowth and dysbiosis in IBD can occur secondary to reduced secretory IgA, creating a vicious cycle 6

Autoimmune Enteropathy

• Presents with intractable diarrhea, lymphoplasmacytic infiltrate in lamina propria, and decreased goblet cells that normally support IgA secretion 1
• Anti-enterocyte antibodies may directly damage the epithelial cells required for IgA transcytosis 1

Celiac Disease

• Active celiac disease causes villous atrophy that disrupts the normal architecture for plasma cell positioning and IgA secretion 1
• Celiac disease co-occurs in 6.6% of patients with IgA deficiency, representing a bidirectional relationship 4

Graft-Versus-Host Disease

• Post-bone marrow transplantation GVHD causes crypt cell necrosis and loss of epithelium, disrupting IgA transcytosis mechanisms 1

Infectious Causes

Parasitic Infections

• Giardiasis can damage intestinal villi where plasma cells reside and where IgA is secreted 1
• Tropical sprue causes changes throughout duodenum, jejunum, and ileum with increased plasma cells but potentially dysfunctional IgA production 1

HIV Enteropathy

• HIV infection decreases CD4+ T lymphocytes that provide help for B cell IgA class switching 1
• Opportunistic infections in HIV further damage intestinal architecture 1

Malnutrition and Systemic Factors

Nutritional Deficiency

• Malnutrition is an independent risk factor for immunodeficiency and impaired antibody production 1
• Protein-energy malnutrition specifically impairs plasma cell function and immunoglobulin synthesis
• Vitamin A deficiency disrupts mucosal immunity and IgA production

Age-Related Factors

• Age is an independent risk factor for immunodeficiency in IBD patients 1
• Elderly patients have reduced B cell responses and antibody production capacity
• Very young children (<4 years) have physiologically lower IgA levels that should not be interpreted as deficiency 2

Critical Clinical Pitfalls

When evaluating low secretory IgA, always obtain a thorough medication history focusing on immunosuppressants, particularly vedolizumab or other anti-integrin therapies that directly block B cell gut homing 1, 6. Check serum immunoglobulin levels (IgA, IgG, IgM) to distinguish selective IgA deficiency from CVID, as the latter requires immunoglobulin replacement therapy 1. In patients with autoimmune disorders or recurrent infections, measure specific antibody responses to vaccines (pneumococcal, tetanus) as these correlate better with clinical symptoms than total immunoglobulin levels alone 5, 7. Consider that combination immunosuppression (corticosteroids plus thiopurines plus biologics) has cumulative effects on secretory IgA that exceed individual drug effects 1.