Are there immunoglobulin abnormalities in inflammatory bowel disease (IBD)?

Immunoglobulin Abnormalities in Inflammatory Bowel Disease

Yes, immunoglobulin abnormalities are common in IBD patients, with low IgG levels occurring in approximately 23% of patients and low IgA in 8%, while paradoxically, some patients exhibit elevated immunoglobulin levels during active inflammation.

Prevalence and Pattern of Immunoglobulin Abnormalities

Low Immunoglobulin Levels (Secondary Immunodeficiency)

• Low IgG occurs in 22.7% of IBD patients, low IgG1 in 23.4%, low IgA in 7.9%, and low IgM in 10.9% 1
• The primary risk factors for developing low IgG levels include increasing age (OR 1.13), hypoalbuminemia (OR 1.83), and longer disease duration (OR 1.40 for low IgG1) 1
• Thiopurine use specifically increases risk of low IgA levels (OR 2.76) 1
• Low IgM levels are associated with increasing age (OR 1.33) and hypoalbuminemia (OR 3.17) 1

Elevated Immunoglobulin Levels During Active Disease

• Total IgG levels are significantly elevated in ulcerative colitis patients compared to Crohn's disease patients, particularly during both active and inactive disease phases 2
• IgG1 concentrations are significantly higher in UC (7.0 mg/ml) compared to CD (5.6 mg/ml), p<0.02 2
• IgG4 levels are significantly elevated in UC (0.39 mg/ml) versus CD (0.29 mg/ml), p<0.05 2
• Conversely, IgG2 levels are higher in CD (4.6 mg/ml) than UC (3.8 mg/ml), p<0.05 2

Disease-Specific Patterns

Crohn's Disease

• IgG1, IgG2, and IgA levels correlate positively with disease activity in CD (p<0.001, p<0.001, and p<0.01 respectively) 2
• IgG levels are lower in CD patients compared to UC/indeterminate colitis patients (p=0.042) 1
• Low IgG/IgG1 levels are associated with increased risk of IBD-related surgery in CD (HR 4.42, p=0.048), particularly small bowel resections (12.8% vs 1.7%, p=0.024) 3

Ulcerative Colitis

• IgG3 levels correlate negatively with disease activity in UC (p<0.01), meaning IgG3 decreases as disease worsens 2
• Total IgG levels remain significantly elevated in UC regardless of disease activity status 2
• IgG and IgA levels are elevated in patients with inflammatory conditions of the ileal pouch (p=0.01 and p=0.003 respectively) 1

Clinical Implications and Outcomes

Impact on Disease Course

• Patients with low IgG/IgG1 levels have worse clinical outcomes, with 62.8% experiencing IBD-related surgeries or hospitalizations compared to 56.9% with normal levels (OR 1.28) 3
• Low immunoglobulin levels are associated with increased need for 5-aminosalicylate initiations (28.2% vs 13.8%, p=0.045) 3
• The presence of concurrent primary sclerosing cholangitis (OR 0.064) and biologic use (OR 0.16) are protective factors associated with normal IgG1 levels 1

Post-Surgical Changes

• Serum IgM concentrations become markedly elevated during the second week after bowel resection, reaching up to 9 times preoperative values, with significantly greater increments in IBD patients compared to controls 4
• This postoperative IgM rise represents 19S polyclonal immunoglobulin and includes increased titers of heterophile antibodies and antibodies against E. coli and Bacteroides 4
• The postoperative IgM elevation does not represent antibody directed against colon antigens and is not specific to IBD 4

Diagnostic and Monitoring Considerations

When to Check Immunoglobulin Levels

• Consider measuring immunoglobulin levels in IBD patients with recurrent infections, poor response to standard therapy, or those requiring escalation of immunosuppression 1, 3
• Monitor for hypoalbuminemia as a marker of risk for developing low immunoglobulin levels 1
• Longer disease duration warrants periodic reassessment of immunoglobulin status 1

Limitations of Immunoglobulin Testing

• Serum immunoglobulin levels cannot reliably differentiate between UC and CD despite distinct patterns 2
• While some IgG subclass concentrations correlate with disease activity, they should be used only as additional markers rather than primary indicators 2
• The clinical utility of routine immunoglobulin monitoring in all IBD patients remains uncertain, as most guidelines do not recommend universal screening 5

Therapeutic Implications

Immunoglobulin Replacement Therapy

• Intravenous immunoglobulin (IVIG) therapy at 2 g/kg induction followed by 200-500 mg/kg maintenance every 2 weeks produced significant reductions in colitis activity scores (13.3 to 4.7, p<0.001) and prednisone requirements (41.7 mg to 1.9 mg daily, p<0.001) in refractory colitis patients 6
• Four of five patients who completed IVIG treatment and improved clinically showed unequivocal reductions in colonic mucosal inflammation on colonoscopy 6
• However, three patients experienced relapses after IVIG discontinuation, suggesting ongoing need for therapy 6
• This remains investigational and requires validation in randomized controlled trials 6

Management of Immunosuppression in Context of Low Immunoglobulins

• IBD patients should not be routinely considered immunocompromised solely due to their disease, but rather through their immunomodulator therapy 5
• Corticosteroids at ≥20 mg prednisolone daily for ≥2 weeks, thiopurines, methotrexate, calcineurin inhibitors, and anti-TNF agents all increase infection risk 5
• The combination of advanced age, malnutrition, and immunomodulator therapy compounds the risk of opportunistic infections in patients with low immunoglobulin levels 5