Immunoprofiling is useful for predicting prognosis in various malignancies and provides targets for immunotherapy. Quantitative multispectral imaging system, which allows simultaneous detection of multiple immune markers, is a novel method for examining the tumor immune environment. We compared the expression levels of various surface markers in immune cells between colitis-associated cancer (CAC) and sporadic colorectal cancer (CRC) and evaluated the clinical usefulness of immunoprofiling in CRC. Tumor specimens from 24 CAC patients and 48 sporadic CRC patients, matched by age, sex, and tumor location to CAC, were included in the analysis. The expression levels of CD3, CD8, Foxp3, and programmed death-ligand 1 (PD-L1) in immune cells at the invasive margins of tumor tissues were evaluated by quantitative multispectral imaging. The CAC group had significantly less levels of cells expressing CD3, CD8, Foxp3, or PD-L1 (all,
p
< 0.01). In the CAC group, patients whose immune cells had high expression of CD3
+
and CD8
+
had better overall survival. The immune profiling patterns of CAC patients were significantly distinct from those of sporadic CRC patients, suggesting that CAC and sporadic CRC have distinct disease phenotypes. Immunoprofiling can be helpful for evaluation of clinical prognosis in CAC.
The study subjects were recruited from child-care centers and kindergartens located in Daedeok-gu, Daejeon between August and September 2018. A total of 411 preschoolers aged 3~6 years were included in the data analyses. A questionnaire of NQ-P, which consisted of 14 checklist items on dietary behaviors, was completed by the parents or guardians of the study subjects. The NQ-P scores and its three factors, including "balance", "moderation", and "environment" factors, were calculated according to sex, age, and weight status. Differences in the NQ-P scores and their factors according to sex, age, and weight status were tested using a student's t-test. Results: The mean NQ-P score of the total subjects was 58.5 ± 9.2, which was within the medium-low grade. The NQ-P score was 58.5 ± 9.4 in boys and 58.6 ± 9.0 in girls (p = 0.955). The NQ-P score was similar regardless of the age groups (57.8 ± 9.4 in 3~4 years vs. 59.2 ± 9.0 in 5~6 years, p = 0.124), whereas subjects aged 5~6 years showed a significantly higher scores of environment factors than those aged 3~4 years (67.9 ± 16.8 vs. 61.7 ± 17.3). The mean score of the moderation factor was lower in the overweight/obese children compared to the non-overweight/obese children (46.6 ± 13.3 vs. 51.0 ± 16.2, p = 0.012). Compared to children aged 3~4 years, children aged 5~6 years had higher intakes of vegetable dishes and processed meat. The overweight/obese group showed a higher consumption of processed beverages than the non-overweight/obese group.
Conclusion:The current study indicates that the dietary behaviors of preschoolers residing in Daejeon need to be improved. These findings suggest that nutrition education or health interventions targeting young children is necessary for improving their nutritional health status.
Background and Aims
Mutations in XIAP can lead to the development of treatment-refractory severe paediatric Crohn's disease [CD], for which hematopoietic stem cell transplantation is the primary therapeutic option. Herein, the interpretation of variants of uncertain significance [VUS] in XIAP must be scrutinized.
Methods
Targeted next-generation sequencing was performed for 33 male paediatric patients with refractory CD admitted at a tertiary referral hospital. To obtain functional data, biomolecular cell assays and supercomputing molecular dynamics simulations were performed.
Results
Nine unrelated male patients harboured hemizygous XIAP variants. Four known pathogenic variants and one novel pathogenic variant [p.Lys168Serfs*12] were identified in five patients, and two novel VUSs [p.Gly205del and p.Pro260Ser] and one known VUS [p.Glu350del] were identified in the remaining four. Among children with VUSs, only the subject with p.Gly205del exhibited defective NOD2 signalling. Using molecular dynamics simulation, we determined that the altered backbone torsional energy of C203 in XIAP of p.G205del was ~2 kcal/mol, suggesting loss of zinc binding in the mutant XIAP protein and poor coordination between the mutant XIAP and RIP2 proteins. Elevated auto-ubiquitination of zinc-depleted p.G205del XIAP protein resulted in XIAP protein deficiency.
Conclusion
A high prevalence of XIAP deficiency was noted among children with refractory CD. Advanced functional studies decreased the subjectivity in the case-level interpretation of XIAP VUSs and directed consideration of hematopoietic stem cell transplantation.
Woo-Jung Songhttps://orcid.org/0000-0002-4630-9922 Tae-Bum Kim https://orcid.org/0000-0001-5663-0640 R E FE R E N C E S 1. Schatz M, Rosenwasser L. The allergic asthma phenotype. J Allergy Clin Immunol Pract. 2014;2:645-648; quiz 649. 2. Romanet-Manent S, Charpin D, Magnan A, Lanteaume A, Vervloet D. Allergic vs nonallergic asthma: what makes the difference? Allergy. 2002;57:607-613. 3. Zissler UM, Esser-von Bieren J, Jakwerth CA, Chaker AM, Schmidt-Weber CB. Current and future biomarkers in allergic asthma. Allergy. 2016;71:475-494. 4. Virchow JC Jr, Kroegel C, Walker C, Matthys H. Cellular and immunological markers of allergic and intrinsic bronchial asthma. Lung. 1994;172:313-334. 5. Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138:700-710. 6. Ali H. Mas-related G protein coupled receptor-X2: a potential new target for modulating mast cell-mediated allergic and inflammatory diseases. J Immunobiol. 2016;1:115. 7. Tatemoto K, Nozaki Y, Tsuda R, et al. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun. 2006;349:1322-1328. 8. Kim TB, Park CS, Bae YJ, Cho YS, Moon HB. Factors associated withseverity and exacerbation of asthma: a baseline analysis of the cohort for reality and evolution of adult asthma in
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