Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, ß7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.

Corneal Langerhans cells in children with celiac disease.

Celiac disease (CeD) is a common small bowel enteropathy characterized by an altered adaptive immune system and increased mucosal antigen presenting cells. This study aims to establish if quantification of corneal Langerhans cells (LCs) using corneal confocal microscopy (CCM) could act as a surrogate marker for antigen presenting cell status and hence disease activity in children with CeD. Twenty children with stable CeD and 20 age-matched controls underwent CCM and quantification of central corneal total, mature and immature LC density. There was no difference in age (11.78 ± 1.7 vs. 12.83 ± 1.91; P = 0.077) or height (1.38 ± 0.14 vs. 1.44 ± 0.13; P = 0.125). BMI (18.81 ± 3.90 vs. 22.26 ± 5.47; P = 0.031) and 25 OHD levels (43.50 ± 13.36 vs. 59.77 ± 22.45; P = 0.014) were significantly lower in children with CeD compared to controls. The total (33.33(16.67-59.37) vs. 51.56(30.21-85.42); P = 0.343), immature (33.33(16.67-52.08) vs. 44.79(29.17-82.29); P = 0.752) and mature (1.56(0-5) vs. 1.56(1.04-8.33); P = 0.752) LC density did not differ between the CeD and control groups. However, immature (r = 0.535, P = 0.015), mature (r = 0.464, P = 0.039), and total (r = 0.548, P = 0.012) LC density correlated with age. Immature (r = 0.602, P = 0.038) and total (r = 0.637, P = 0.026) LC density also correlated with tissue transglutaminase antibody (Anti-TtG) levels assessed in 12/20 subjects with CeD. There was no difference in corneal LC density between children with CeD and controls. However, the correlation between corneal LC density and anti-TtG levels suggests a relationship with disease activity in CeD and requires further study.

Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease.

OBJECTIVES: The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. METHODS: This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. RESULTS: Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). CONCLUSION: Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.

Outcome associated with EPCAM founder mutation c.499dup in Qatar.

Tufting enteropathy (TE) is a rare autosomal recessive congenital enteropathy that usually requires long-term parenteral nutrition (PN). In the Arabic Peninsula, four distinct EPCAM mutations have been identified to cause TE. As consanguineous marriages are socially favored, pre-marital and pre-conception testing has become a critical disease prevention strategy. This study aimed to identify the pathogenic EPCAM mutations causing TE in Qatari families and determine possible genotype-phenotype correlations. Twenty-two TE patients from seven multiplex families with TE were identified. Blood samples were collected from patients and first-degree relatives. Exons of the gene were amplified and sequenced. Retrospective chart review and/or family interviews were conducted to determine phenotypic characteristics of the disease. Sequence analysis revealed a single, previously described c.499dup mutation in exon 5 of all families tested, suggesting a founder effect. Of the 18 patients whose full clinical information was available, three patients (17%) were off PN with a good quality of life, without intestinal transplantation, and one (6%) was receiving partial PN. Our patients with TE were severely stunted compared to a similar group of patients receiving long-term PN for short bowel syndrome, suggesting that this could possibly be due to TE rather than secondary to inadequate nutrition. Our study identified the EPCAM mutation c.499dup as the genetic defect causing TE in all the participant Qatari families. This finding should facilitate early diagnosis of TE and genetic counseling. Furthermore, it should aid in the prevention of TE through pre-marital screening, antenatal diagnosis, and pre-implantation genetic diagnosis.