New serological markers in pediatric patients with inflammatory bowel disease

The spectrum of serological markers associated with inflammatory bowel disease (IBD) is rapidly growing. Due to frequently delayed or missed diagnoses, the application of non-invasive diagnostic tests for IBD, as well as differentiation between ulcerative colitis (UC) and Crohn’s disease (CD), would be useful in the pediatric population. In addition, the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody (pANCA) improved the sensitivity of serological markers in pediatric patients with CD and UC. Some studies suggested that age-associated differences in the patterns of antibodies may be present, particularly in the youngest children. In CD, most patients develop stricturing or perforating complications, and a significant number of patients undergo surgery during the disease course. Based on recent knowledge, serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery. Pediatric UC is characterized by extensive colitis and a high rate of colectomy. In patients with UC, high levels of anti-CBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis. Thus, serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression. In conclusion, identification of patients at an increased risk of rapid disease progression is of great interest, as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD, and reduce complications and hospitalizations.

Suspected SARS-CoV-2 infection with fever and coronary heart disease:A case report

BACKGROUND The coronavirus disease 2019(COVID-19)is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Suspected cases accounted for a large proportion in the early stage of the COVID-19 outbreak.The deviation of the nucleic acid test by throat swab(the current gold standard of COVID-19)caused by variation in sampling techniques and reagent kits and coupled with nonspecific clinical manifestations make confirmation of the suspected cases difficult.Proper management of the suspected cases of COVID-19 is crucial for disease control.CASE SUMMARY A 65-year-old male presented with fever,lymphopenia,and chest computed tomography(CT)images similar to COVID-19 after percutaneous coronary intervention.The patient was diagnosed as having bacterial pneumonia with cardiogenic pulmonary edema instead of COVID-19.This was based on four negative results for throat swab detection of SARS-CoV-2 nucleic acid using reverse transcriptase-polymerase chain reaction assay and one negative result for serological antibody of SARS-CoV-2 with the serological assay.Additionally,the distribution of ground-glass opacities and thickened blood vessels from the CT images differed from COVID-19 features,which further supported the exclusion of COVID-19.CONCLUSION Distinguishing COVID-19 patients from those with bacterial pneumonia with cardiogenic pulmonary edema can be difficult.Therefore,it requires serious identification.

Tissue transglutaminase levels above 100 U/mL and celiac disease:A prospective study

AIM:To investigate whether a tissue-transglutaminase antibody(tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease(CD).METHODS:Children suspected of having CD were prospectively included in our study between March 2009 and September 2011.All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study.Anti-endomysium antibodies(EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus(EUROIMMUN,Luebeck,Germany).Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase(ELiA Celikey IgA kit Phadia AB,Uppsala,Sweden).The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber.Marsh Ⅱ and Ⅲ lesions were considered to be diagnostic for the disease.The positive predictive values(PPVs),negative predictive values(NPVs),sensitivity and specificity of EMA and tTGA along with their 95% CI(for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD.RESULTS:A total of 183 children were included in the study.A total of 70(38.3%) were male,while 113(61.7%) were female.The age range was between 1.0 and 17.6 years,and the mean age was 6.2 years.One hundred twenty(65.6%) patients had a small intestinal biopsy diagnostic for the disease;3 patients had a Marsh Ⅱ lesion,and 117 patients had a Marsh Ⅲ lesion.Of the patients without CD,only 4 patients had a MarshⅠlesion.Of the 183 patients,136 patients were positive for EMA,of whom 20 did not have CD,yielding a PPV for EMA of 85%(95% CI:78%-90%) and a corresponding specificity of 68%(95% CI:55%-79%).The NPV and specificity for EMA were 91%(95% CI:79%-97%) and 97%(95% CI:91%-99%),respectively.Increased levels of tTGA were found in 130 patients,although only 116 patients truly had histological evidence of the disease.The PPV for tTGA was 89%(95% CI:82%-94%),and the corresponding specificity was 78%(95% CI:65%-87%).The NPV and sensitivity were 92%(95% CI:81%-98%) and 97%(95% CI:91%-99%),respectively.A tTGA level ≥ 100 U/mL was found in 87(47.5%) patients,all of whom were also positive for EMA.In all these 87 patients,epithelial lesions confirming CD were found,giving a PPV of 100%(95%CI:95%-100%).The corresponding specificity for this cutoff value was also 100%(95% CI:93%-100%).Within this group,a total of 83 patients had symptoms,at least gastrointestinal and/or growth retardation.Three patients were asymptomatic but were screened because they belonged to a group at risk for CD(diabetes mellitus type 1 or positive family history).The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding.CONCLUSION:This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.

Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health worldwide.As the humoral immune response plays essential roles in disease occurrence and development,understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease.In this review,we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARSCoV-2-specific humoral immunity and the critical role of this immunity in vaccine development.Notably,serological antibody testing based on the humoral immune response can guide public health measures and control strategies;however,it is not recommended for population surveys in areas with very low prevalence.Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection,whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults.The correlations between antibody(especially neutralizing antibody)titers and protection against SARS-CoV-2 reinfection should be further examined.In addition,the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.