Hashash, Jana G.

Abstract Background Severe Crohn’s disease [CD] can result in extensive bowel resections and need for creation of an ileostomy. Faecal calprotectin [FC] is well studied in CD management, though its role in patients who have an ileostomy is unclear. Our aim is to understand if FC is a useful adjunct to radiographic or endoscopic studies in identifying recurrent CD after surgery in patients with an ileostomy. Methods Between January 1, 2017, and September 30, 2020, we searched the Mayo Clinic electronic medical record retrospectively for adult patients with ICD-10 code for CD, and a surgical history of an ileostomy. Patients were included in the analysis if they had at least one FC measured and a concomitant radiographic imaging and/or endoscopic procedure. An abnormal FC was defined as greater than 60 µg/g. Results Of 51 patients who met our inclusion criteria, 17 had an FC level >60 µg/g. Of these 17 patients, 14 had imaging and/or an ileoscopy confirming the presence of small bowel inflammation, with a sensitivity of 87.5%. Of the remaining 34 patients with an FC level ≤60 µg/g, 32 patients had imaging and/or ileoscopy demonstrating no small bowel inflammation, with a specificity of 91.4%. FC from an ileostomy effluent had a positive predictive value of 82.3%, a negative predictive value of 94.1% and test diagnostic accuracy of 90.1%. Conclusion FC from an ileostomy effluent is a highly sensitive and specific test for the assessment and monitoring of small bowel inflammation and disease recurrence in patients with CD.

Abstract Background Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. Methods We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. Results We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. Conclusions An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.