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The region on chromosome 6 encoding the major histocompatibility complex (MHC) is associated with a number of autoimmune and infectious diseases. Primary susceptibility to many of these has been localized to a region containing the human leukocyte antigen (HLA)-DR and -DQ genes. A recent study of sarcoidosis has provided evidence of an independent effect, associated with a truncating single nucleotide polymorphism (SNP) of a nearby gene, BTNL2. This gene may encode an immune receptor involved in costimulation. Sarcoidosis, tuberculoid leprosy, tuberculosis (TB) and Crohn’s disease all have similar immunological features, including a Th1 response with granuloma formation. In addition mycobacteria have been identified or suggested to be causative pathogens in such conditions. We genotyped the truncating BTNL2 SNP in 92 TB and 72 leprosy families from Brazil and carried out family-based association studies. We could not find evidence of overtransmission of the truncating allele in TB. There was an association with susceptibility to leprosy ( P = 0.04), however, this is most likely due to linkage disequilibrium with HLA-DR. We also genotyped 476 UK Caucasian cases of Crohn’s disease with 760 geographically matched controls and found no evidence of a disease association. We conclude that the truncating BTNL2 SNP is not important in this group of Th1 dominated granulomatous diseases. [ABSTRACT FROM AUTHOR]

The prevalence of inflammatory bowel disease (IBD) is higher in these patient groups.[[1]] We describe two patients who developed acute life-threatening colitis following subcutaneous secukinumab. GLO:DF2/01apr20:ced14149-fig-0001.jpg PHOTO (COLOR): Deep ulceration in the rectum on flexible sigmoidoscopy, demonstrating acute severe colitis (patient 1). gl Patient 2 was a 38-year-old man who commenced secukinumab 150 mg monthly for severe AS in May 2013, following secondary loss of response to adalimumab. A trial of secukinumab for IBD unexpectedly showed worse outcomes in the active treatment arm.[[1]] In the pivotal AS secukinumab trials, five patients treated with secukinumab developed either I de novo i colitis or exacerbations of existing colitis.[[3]] In conclusion, we report two patients with acute severe colitis following secukinumab therapy, with life-threatening complications requiring hospitalization. [Extracted from the article]

Background and aims: Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G-207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci. Methods: A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA. Results: OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p=0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D' 0.79 and 0.88, and r²=0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale. Conclusions: The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD. [ABSTRACT FROM AUTHOR]

Background: The deployment of self expanding enteral stents via endoscopic and fluoroscopic guidance has emerged as effective treatment of large bowel obstruction in both the acute and elective setting. Methods: 20 consecutive patients (10 male), with a median age of 72 years were studied between 1997 and 2002 on an intention to treat basis. All patients had symptomatic large bowel strictures. Results: 26 procedures were performed on 20 patients. A total of 15 stents were inserted with successful placement on the first attempt in 13 procedures. One patient was stented on the second occasion and one patient was stented on the fourth occasion. In 5 patients (6 procedures) a wire could not be passed due to complete occlusion of the lumen or due to the position of the carcinoma which prevented viewing 'en face". The remainder of the failures were due to poor preparation of the colon, or the stenosis being too lax to be amenable to stenting. The cause of the stenosis was malignant in 19 cases with the sites being rectosigmoid (45%), sigmoid colon (40%), splenic flexure (10%), transverse colon (5%). Symptoms improved in all patients successfully stented but in one patient there was distal migration of the stent 3 days later. In the others good palliation was obtained with a median symptom free survival of 7 months. 14 patients died in follow up due to causes unrelated to stent insertion. Conclusion: Colonic stents have an important place in the management of large bowel obstruction and palliation of colonic carcinoma and should be available in any district general hospital. [ABSTRACT FROM AUTHOR]