Diagnostic and clinical significance of Crohn’s disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA:New anti-MZGP2 ELISA in Crohn’s

The recent identification of the pancreas major zymogen granule membrane glycoprotein 2 (MZGP2) as the major autoantigen of pancreatic autoantibody (PAB) has led to the appreciation of anti-MZGP2 antibodies as specific markers of Crohn’s disease (CrD). We have recently developed new, robust, highly sensitive and specific IgA and IgG anti-MZGP2 antibody ELISAs and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date for anti-MZGP2 antibodies. In contrast to currently available anti-MZGP2 ELISAs, the new QUANTA Lite® MZGP2 ELISA (INOVA Diagnostics, San Diego, CA) utilizes the eukaryotically-expressed specific isoform 4 of human GP2 UniProtKB: P55259. A total of 832 sera were studied including 617 consecutive IBD patients (323 CrD and 294 UC) under regular follow-up in a tertiary centre, 112 patients with various diseases, and 103 healthy blood donors. The new ELISA’s calculated AUC was 0.5968, 95% CI (0.5552, 0.6383) for IgA anti-MZGP2 [CD vs non-CD (UC plus controls)] and 0.6236, 95% CI (0.5813, 0.6659) for IgG anti-MZGP2. The sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and the specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 was 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75% (70, 80) and specificity of 84% (79, 89). Of clinical relevance, IgA anti- MZGP2 antibodies were more prevalent in patients with early disease onset (Montreal classification A1, p=0.011), while patients with localised colonic disease were less likely to be IgG anti-MZGP2 positive. Anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement and stricture formation. Patients with longer disease duration were more likely to have IgG anti-MZGP2 or IgA ASCA antibodies. In conclusion, the new IgA and IgG anti-MZGP2 antibody ELISAs allow accurate autoantibody determination, and can be used as a tool to study the clinical significance and utility of these autoantibodies in patients with IBD

At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension

Hypertension affects 1–5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12 years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review

Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials

Current health status and medical therapy of patients with pediatric-onset inflammatory bowel disease: A survey-based analysis on 1280 patients aged 10-25 years focusing on differences by age of onset.

OBJECTIVE: There are inconsistent reports on age-related differences in inflammatory bowel disease (IBD). On the basis of patient information, we describe the clinical presentation and therapy in relation to age at diagnosis in longstanding pediatric IBD. PATIENTS AND METHODS: Two surveys were conducted in children and young adults (age: 10-25 years) by pretested postal questionnaires. The main analyses are descriptive, showing proportions and distributions per grouped age of diagnosis. Exploratory logistic regression was used to identify sociodemographic and disease-related factors associated with prognosis. Recent disease course, use of biological therapy, and resecting surgery were chosen as indicators of disease severity. Patients with a diagnosis in infancy (<2 years of age) are presented as a case series. RESULTS: Information of 1280 cases was available [804 Crohn's disease (CD), 382 ulcerative colitis (UC), 94 IBD not specified] (response: 44.6 and 49.6%). Stable remission during the preceding year was reported by 675 (56.7%) patients; 825 (60.9%) patients reported feeling currenty well. Anti-tumor necrosis factor therapy was reported by 33% of CD patients and 9.3% of UC patients, immunomodulation in 82.1 and 63.2%, and corticosteroids by 78.4 and 76.1%, respectively (ever use). Age at diagnosis was not associated with indicators of severe disease. Diagnosis in infancy was reported by 37 patients. CONCLUSION: Our data do not support age at diagnosis-related differences in prognosis in pediatric-onset IBD

Randomized controlled clinical trial of all-ceramic single-tooth implant reconstructions using modified zirconia abutments: results at 5 years after loading

The objective of this trial study was to assess whether submucosal veneering of internally connected zirconia abutments influences clinical, radiographic, and technical outcomes of single-tooth implant-borne reconstructions at 5 years after loading. A total of 20 patients with 20 single-tooth implants in the anterior or premolar area of the maxilla or mandible were included. The implants were randomly restored with fixed single-tooth reconstructions using either pink-veneered customized zirconia abutments (test group = 10) or nonveneered customized zirconia abutments (control group = 10). All reconstructions were adhesively cemented with all-ceramic crowns. Follow-up examinations were performed at baseline (7 to 10 days after crown insertion) and at 1, 3, and 5 years after loading, at which points the following were assessed: periodontal parameters such as probing depth (PD), bleeding on probing (BOP), and marginal bone levels, as well as technical outcomes using the modified United States Public Health Service (USPHS) criteria. Statistical comparisons were based on the Wilcoxon-Mann-Whitney test. Sixteen patients attended the 5-year follow-up. At 5 years, the implant survival rate was 100% and the prosthetic survival rate was 94.1% (one abutment fracture in the test group). Veneering of the submucosal part of zirconia abutments resulted in significantly higher mean PD values: 3.6 ± 0.4 mm (test group) and 3.0 ± 0.5 mm (control group), P = .042. Marginal bone levels at 5 years and changes up to 5 years were not significantly different between groups (P > .05). One crown exhibited an abutment fracture and two crowns a minor chipping (17.6% overall technical complication rate). Limited by a small sample size, veneering of the submucosal part of internally connected zirconia abutments led to outcomes that were less favorable biologically (PD, BOP, and KM), but similar to nonveneered abutments radiographically and technically