Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease

Abstract

Background: Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period.

Methods: This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization.

Results: A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis.

Conclusion: A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

Keywords: Globulin; albumin; inflammatory bowel disease; quality of life; total protein.

Figure 1

Kaplan-Meier curve for hospitalization and inflammatory bowel disease (IBD)-related surgeries amongst IBD patients with high globulin fraction vs. normal globulin fraction: (A) hospitalization in Crohn’s disease patients, (B) hospitalization in ulcerative colitis patients, (C) IBD-related surgeries in Crohn’s disease patients, (D) IBD-related surgeries in ulcerative colitis patients

Figure 2

Cox regression survival analysis for hospitalization and inflammatory bowel disease (IBD)-related surgeries amongst patients with a high globulin fraction vs. normal globulin fraction. (A) Crohn’s disease patients and hospitalization, (B) ulcerative colitis patients and hospitalization, (C) Crohn’s disease patients and IBD-related surgeries, and (D) ulcerative colitis patients and history of IBD-related surgeries. All of these results are after controlling for differences in age, sex, history of IBD-surgery, presence of anemia, elevated C-reactive protein and hypoalbuminemia on the day of globulin fraction testing