African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity.

The TNF alpha-induced protein 3 (TNFAIP3) is an ubiquitin-modifying enzyme and an essential negative regulator of inflammation. Genome-wide association studies have implicated the TNFAIP3 locus in susceptibility to autoimmune disorders in European cohorts, including rheumatoid arthritis, coronary artery disease, psoriasis, celiac disease, type 1 diabetes, inflammatory bowel disease, and systemic lupus erythematosus (SLE). There are two nonsynonymous coding polymorphisms in the deubiquitinating (DUB) domain of TNFAIP3: F127C, which is in high-linkage disequilibrium with reported SLE-risk variants, and A125V, which has not been previously studied. We conducted a case-control study in African-American SLE patients using these coding variants, along with tagging polymorphisms in TNFAIP3, and identified a novel African-derived risk haplotype that is distinct from previously reported risk variants (odds ratio=1.6, p=0.006). In addition, a rare protective haplotype was defined by A125V (odds ratio=0.31, p=0.027). Although A125V was associated with protection from SLE, surprisingly the same allele was associated with increased risk of inflammatory bowel disease. We tested the functional activity of nonsynonymous coding polymorphisms within TNFAIP3, and found that the A125V coding-change variant alters the DUB activity of the protein. Finally, we used computer modeling to depict how the A125V amino acid change in TNFAIP3 may affect the three-dimensional structure of the DUB domain to a greater extent than F127C. This is the first report of an association between TNFAIP3 polymorphisms and autoimmunity in African-Americans.

Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia.

Although inflammatory bowel disease is a well-described feature of glycogen storage disease type Ib, it has been reported in only a small number of individuals with glycogen storage disease type Ia (GSDIa). We describe, to our knowledge, the first patient with GSDIa and very early-onset inflammatory bowel disease (VEO-IBD). Larger studies are needed to better understand this possible association, elucidate the mechanism of VEO-IBD in GSDIa, and inform management.

Structured Reporting of Magnetic Resonance Enterography for Pediatric Crohn's Disease: Effect on Key Feature Reporting and Subjective Assessment of Disease by Referring Physicians.

PURPOSE: To objectively compare the content of structured reports (SR) vs nonstructured reports (NSR) for magnetic resonance enterography (MRE) of pediatric patients with Crohn's disease, and to evaluate referring clinicians' subjective assessment of reports. METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 25 pediatric subjects (15 male, 10 female; mean age = 14 years [range: 9-18 years]) with Crohn's disease imaged with MRE. Three radiologists independently interpreted all examinations using both NSR and SR, separated by 4 weeks. Reports were assessed for documentation of the presence or absence of 15 key reporting features. A total of 30 reports (15 NSR [5 per reader] and 15 SR [5 per reader]) were randomly selected for review by 3 referring physicians, who subjectively evaluated the reports independently. RESULTS: NSR documented the presence or absence of 7.7 ± 2.5 key features, whereas SR documented 14.0 ± 0.8 features (P < 0.001). SR resulted in increased documentation of 12 of 15 features including stricture (P < 0.001), fistula (P < 0.001), fluid collection (P = 0.003), and perianal disease (P < 0.001). Referring physicians preferred SR regarding ease of information extraction, clarity of anatomy, and ability to identify disease phenotype (P < 0.01 for each). CONCLUSION: The use of structured reporting in describing pediatric Crohn's disease, MRE resulted in significantly increased reporting of key features. Referring clinicians also demonstrated a subjective preference for SR.