Serum IgG4 Subclass Deficiency Defines a Distinct, Commonly Encountered, Severe Inflammatory Bowel Disease Subtype
| Autor: | Dmitriy Babichenko, Douglas J. Hartman, Jorge D. Machicado, Filippos Koutroumpakis, Siobhan Proksell, Liza Konnikova, Jeffrey Dueker, Anna E. Phillips, Hasieb Din, Dhiraj Yadav, Claudia Ramos Rivers, Janet Harrison, Maaz Ahsan, Arthur Barrie, David G. Binion, Gong Tang, Marc Schwartz, Xiaoqing Tan, Elyse Johnston, Michael A. Dunn, Jana G. Hashash |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
education.field_of_study business.industry Cholangitis Sclerosing Population Gastroenterology Inflammatory Bowel Diseases medicine.disease Inflammatory bowel disease Ulcerative colitis Subclass Primary sclerosing cholangitis Immunoglobulin G Internal medicine parasitic diseases Severity of illness Cohort Humans Immunology and Allergy Medicine Population study business education Biomarkers |
| Zdroj: | Inflammatory Bowel Diseases. 27:855-863 |
| ISSN: | 1536-4844 1078-0998 |
| DOI: | 10.1093/ibd/izaa230 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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