Fecal calprotectin, MMP-9, and human beta-defensin-2 levels in pediatric inflammatory bowel disease

Purpose

Fecal MMP-9 and human beta-defensin-2 (HBD-2) levels, potential markers of intestinal inflammation, are insufficiently explored in pediatric inflammatory bowel disease (IBD). The aim was to study fecal MMP-9 and HBD-2 in pediatric IBD to compare their performance to calprotectin and to study whether they would provide additional value in categorizing patients according to their disease subtype.

Methods

Fecal calprotectin, MMP-9, and HBD-2 levels were measured with ELISA in 110 pediatric patients with IBD (Crohn’s disease, n?=?68; ulcerative colitis (UC), n?=?27; unclassified, n?=?15; median age, 14). To compare the performance of the fecal markers, the area under the receiver operating characteristics curve (±95 % CI) was used. In addition, the best cut-off values of each measure to differentiate IBD patients and controls (n?=?27 presenting with diarrhea, abdominal pain, and/or anemia) were derived by maximizing sensitivity and specificity.

Results

Of the fecal markers studied, calprotectin performed best for separation of IBD and non-IBD patients with the area under curve (AUC) of 0.944 (95 % CI, 0.907 to 0.981). For MMP-9, AUC was 0.837 (95 % CI, 0.766 to 0.909), the levels being significantly higher in active IBD and in UC compared with Crohn’s disease (p?=?0.0013), but categorization of these patient groups did not take place. HBD-2 did not categorize any of the studied groups.

Conclusions

Calprotectin was the best fecal marker in pediatric IBD, but MMP-9 showed almost comparable performance in UC, suggesting applicability as a surrogate marker of inflammation. Fecal HBD-2 did not bring information to the disease characteristics of pediatric IBD patients.     

Inflammatory bowel disease: A survey of the epidemiology in Asia

Inflammatory bowel disease (IBD) has long been considered a disease that affects predominantly a Western population. The incidence and prevalence rates from Asian populations are much lower in comparison. More recent data, however, have shown significantly higher rates in Asians and time trend studies have shown an increase in the incidence of ulcerative colitis (UC) and a similar but lower rise in Crohn's disease (CD). The epidemiological changes that are taking place mirror that of the Western experience seen 50 years previously and seem to occur in parallel with the rapid socioeconomic development taking place in Asia. It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South‐East Asia have higher rates compared to Chinese and Malays. While there is host genetic predisposition, environmental factor(s) may be responsible for this difference. Migrant studies of South Asians in the UK, where second‐generation immigrants have assumed incidence rates as high as the indigenous whites and Asian Jews who develop high incidence rates comparable to Jews from Europe or North America in Israel point to the role of environmental factors. It is unclear which specific factors are responsible. Studies have suggested a change in diet to a more Westernized one may underlie this epidemiological change in the Asian population. It is likely that there are racial groups amongst Asians who are more susceptible to IBD and who will demonstrate a higher frequency of IBD when exposed to putative environmental factors.     

Potentiating Functional Antigen-specific CD8+ T Cell Immunity by a Novel PD1 Isoform-based Fusion DNA Vaccine

Understanding and identifying new ways of mounting an effective CD8⁺ T cell immune response is important for eliminating infectious pathogens. Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking this PD1/PD-L pathway could functionally rescue the “exhausted” T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Here, we identified a new isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells (PBMCs). Δ42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. We utilized Δ42PD1 as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen to immunize mice, which elicited a significantly enhanced level of anti-p24 IgG1/IgG2a antibody titers, and important p24-specific and tetramer⁺CD8⁺ T cells responses that lasted for ≥7.5 months. Furthermore, p24-specific CD8⁺ T cells remain functionally improved in proliferative and cytolytic capacities. Importantly, the enhanced antigen-specific immunity protected mice against pathogenic viral challenge and tumor growth. Thus, this newly identified PD1 variant (Δ42PD1) amplifies the generation of antigen-specific CD8⁺ T cell immunity when used in a DNA vaccine.     

Evaluation of three substitutes for Percoll in sperm isolation by density gradient centrifugation

Silane-coated silica particle solutions (ISolate(TM) and PureSperm)TM)) and iodixanol (OptiPrep(TM)) were compared to polyvinylpyrrolidone (PVP)-coated silica particles (Percoll(TM)) in their efficacy to recover spermatozoa by gradient centrifugation for use in assisted reproductive procedures. Efficacy was assessed in terms of percentages of sperm recovery, sperm vitality and motility, normal sperm morphology and normal sperm chromatin condensation. No significant difference was found in the recovery of spermatozoa for men with both normal sperm counts and oligozoospermia, between PVP-coated and silane-coated particle solutions. Iodixanol had significantly lower sperm recovery compared to the other products. Sperm vitality, progressive motility, normal morphology and normal chromatin condensation did not differ significantly between any of the sperm isolation products.      

Emergence of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae during the years 2000 and 2004 in Helsinki,Finland

The molecular epidemiology of 33 Escherichia coli and 81 Klebsiella pneumoniae extended-spectrum β-lactamase-producing health-care-associated and community-acquired isolates collected in the Helsinki district during 2000–2004 was investigated. Clonality studies, antimicrobial susceptibility and genotyping of the isolates were performed. Newly emerging CTX-M-producing E. coli and bla_SHV-12-producing K. pneumoniae isolates were detected. Clonal clusters of both species persisted throughout the study period.