Impact of Low Immunoglobulin Levels on Disease Outcomes of IBD

Abstract

Introduction: Inflammatory bowel disorders (IBD) have been considered immune-mediated disorders with dysregulated innate and adaptive immunities. However, the treatment failure of immunosuppressive agents is common. One theory behind this failure is secondary humoral and/or cellular immune deficiency. There remains a lack of investigation into quantifiable clinical outcomes of patients with IBD in the setting of low Ig levels. We aimed to identify an association between low Ig levels in IBD patients and poor clinical outcomes. Methods: A case-controlled analysis was performed on subjects with Crohn's disease (CD) and ulcerative colitis (UC) with measured IgG and IgG1 levels obtained from April 2002 through December 2014. Exclusion criteria included those with known primary immunodeficiency disorder and those with HIV. Poor disease outcomes were defined primarily as the need for IBD-related bowel resection or nonsurgical IBD-related hospitalizations following documented Ig levels. Other outcomes measured included C. difficile/CMV infection and any escalation of the patient's prior drug regimen. Demographic and clinical characteristics were measured, and univariate and multivariate analyses were performed. Results: A total of 82 IBD patients (50% female, 20 with UC and 62 with CD) had documented IgG/G1 levels. 27 (33%) had normal IgG/G1 levels and 55 (67%) had a deficiency. 15 (55.6%) patients with normal Ig levels were found to have poor clinical outcomes defined as documented IBD-related surgery or hospitalization, while 38 (69.1%) patients with low levels experienced poor outcomes (p=0.23). All 8 patients requiring small bowel resection had IgG/G1 deficiency (p=0.048). Risk factors associated with poor outcomes included immunomodulator use (p=0.008), regular antibiotic use (p=0.042), elevated hgb and albumin levels (p=0.002, p=0.001), and number of hospitalizations prior to levels (p < 0.001). In the MV analysis, risk factors associated with poor outcomes included increased hospitalizations prior to drawn levels (OR=1.5, p=0.029). Other trends included an increased albumin level (OR=0.52, p=0.097), immunomodulator use (OR=5.91, p=0.12), and IgG/G1 deficiency (OR=1.5, p=0.69). Conclusion: Our study demonstrated a trend towards poor clinical outcomes in IBD patients with lower Ig levels. This suggests that boosting humoral immunity might be beneficial for select IBD patients. This, in turn, suggests clinical implications for future treatment options in this patient subset.Figure 1Figure 2Figure 3