IBD and Stool Secretory IgA Levels
IBD is associated with LOW secretory IgA (SIgA) in stool, not high levels. This represents a breakdown in mucosal immune homeostasis where the normal IgA-dominant intestinal immune response is disrupted.
The Mucosal Immune Shift in IBD
In active IBD, there is a fundamental shift away from the normal IgA-predominant mucosal immune response:
Normal intestinal mucosa is dominated by IgA, which maintains tolerance to commensal bacteria and provides non-inflammatory immune surveillance 1
In active IBD, particularly Crohn's disease and ulcerative colitis, mucosal IgG production dramatically increases while IgA responses become relatively deficient 1, 2
Mucosal IgG concentrations are markedly elevated in active UC (median 512 μg/ml) and active CD (256 μg/ml) compared to controls with irritable bowel syndrome (1.43 μg/ml), while total mucosal IgA concentrations do not differ significantly from controls 1
Evidence for Reduced IgA Function in IBD
The functional capacity of IgA in IBD is compromised:
IgA antibody titers against fecal bacteria are significantly lower in UC compared to controls (p < 0.01), indicating impaired mucosal IgA responses despite normal total IgA levels 1
This represents a breakdown of tolerance to normal commensal gut flora, with the immune system shifting to a more inflammatory IgG-mediated response rather than the homeostatic IgA response 1
The exaggerated mucosal immune response in IBD is directed against cytoplasmic proteins of intestinal bacteria, particularly prominent in active Crohn's disease 1
Systemic Immunoglobulin Patterns
While mucosal IgA is functionally deficient, systemic immunoglobulin patterns show different alterations:
Serum IgG levels are elevated in IBD patients, particularly IgG1 in UC (7±0.77 mg/ml vs 5.6±0.61 mg/ml in CD, p<0.02) 3
Low serum IgA levels occur in 7.9% of IBD patients, with risk factors including increasing age, disease duration, hypoalbuminemia, and thiopurine use 4
The presence of low serum IgA does not necessarily correlate with mucosal IgA levels, as the mucosal and systemic compartments function somewhat independently 4, 3
Clinical Implications
The shift from IgA to IgG-mediated mucosal immunity has important pathophysiologic consequences:
IgG-mediated immune responses are inherently more inflammatory than IgA responses, contributing to tissue damage in IBD 2
The loss of normal IgA-mediated tolerance mechanisms allows aberrant immune responses to commensal bacteria, perpetuating intestinal inflammation 1
This immune dysregulation is most pronounced during active disease and correlates with disease activity markers 1, 3