Background/purposeEndothelium is a key element in the regulation of vascular homeostasis and its alteration can lead to the development of vascular diseases. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with potential extensive vascular lesions, involving skin vessels, renal glomeruli, cardiovascular system, brain, lung alveoli, gastrointestinal tract vessels and more. We aimed to assess endothelial dysregulation related biomarkers in pediatric-onset SLE (pSLE) patient serum and elucidate its correlation with their clinical features, laboratory parameters, and the overall disease activity.MethodsDisease activities were evaluated by SLE disease activity index (SLEDAI). Patient characteristics were obtained by retrospective chart review. Six biomarkers associated with endothelial dysregulation, including Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie2, Vascular endothelial growth factor (VEGF), thrombomodulin, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) were tested through enzyme-linked immunosorbent assay (ELISA) measurement.ResultsThis study comprised 118 pSLE patients. Data from 40 age-matched healthy controls were also obtained. The mean diagnostic age was 13 ± 4.12 years-old and 90.7% are females. Serum levels of VEGF, Tie2, thrombomodulin were significantly higher while serum ADAMTS13 was lower in active pSLE patients when compared to those with inactive diseases (all p < 0.05). In organ specific association, serum thrombomodulin level was higher in pSLE patient with renal involvement, and serum ADAMTS13 levels was negatively associated with neurological involvement (p < 0.05). A cutoff of thrombomodulin at 3333.6 pg/ml best correlated renal involvement. (AUC = 0.752, p < 0.01).ConclusionEndothelial dysregulation associating proteins seems to be potent biomarkers for pSLE activity as well as organ involvement in pSLE patients. These biomarkers may be beneficial in understanding of the vascular pathogenesis and disease monitoring.

Background: Some studies have shown associations of maternal age at delivery with asthma and food allergy in offspring. However, the relationship between maternal age at delivery and allergic rhinitis is largely unclear. This study aimed to investigate the association between maternal age at delivery and allergic rhinitis in a population sample of Asian children, and to explore potential effect modifiers.Methods: A total of 1344 singleton-birth children (763 boys, 56.8%; mean age, 6.4 years) participating in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort were evaluated by a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and interviewed by pediatricians. Allergic sensitization was determined by using Phadiatop Infant. Multiple logistic regression models with covariates adjustment were performed to investigate the association of maternal age at delivery with allergic rhinitis and allergic sensitization in offspring.Results: Among 1344 study children, 793 (59%) had physician-diagnosed allergic rhinitis.Advanced maternal age at delivery (!40 years) was significantly associated with increased odds of allergic rhinitis (adjusted odds ratio [AOR] ¼ 4.58, 95% confidence interval [CI]: 1.90-11.03) and allergic sensitization (AOR ¼ 2.86, 95% CI: 1.13-7.22) in offspring. A sex-stratified analysis revealed that the association of advanced maternal age with allergic rhinitis was statistically significant only in female offspring (AOR ¼ 7.02, 95% CI: 1.89-26.14). Stratified analyses by birth order or environmental tobacco smoke exposure during pregnancy did not reveal any significant differences. Conclusion:Advanced maternal age at delivery was associated with increased risk of allergic rhinitis in Asian children, probably more pronounced among girls.

Background Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5. Case presentation Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy. Conclusions Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.

BackgroundPatients with T cell deficiency &lt;10% of normal proliferation are indicated to receive immune reconstruction by hematopoietic stem cell transplantation (HSCT). This study aimed to investigate whether non-radioactive assays can be used to quantitatively detect the lymphocyte proliferation &lt;10% of normal as radioactive [3H]-thymidine.”MethodsRadioactive [3H]-thymidine, non-radioactive carboxyfluorescein diacetate succinimidyl ester (CFSE), and Ki-67 protein expressions were used to measure the lymphocyte proliferation as calculated using the stimulation index (SI), subtraction percentage, and proliferation index (FlowJo software). Normal references were established for comparison in the absence of parallel healthy controls.ResultsNormal ranges of mitogen-stimulated lymphocyte proliferation were established as a SI of 15–267 (CSFE 47–92%, Ki-67 42–79%) with phytohemagglutinin (PHA) 5 μg/ml stimulation; 19–139 (CFSE 62–83%, 45–74% Ki-67) with concanavalin-A (ConA) 5 μg/ml stimulation; 7–53 (CFSE 6–23%, Ki-67 10–24%) with pokeweed mitogen (PWM) 0.1 ug/ml stimulation; 3–28 (CFSE 4–10%, Ki-67 5–14%) with candida 10 ug/ml stimulation; and 2–27 (CFSE 6–41%, Ki-67 6–30%) with bacille Calmette-Guerin (BCG) 0.02 ng/ml stimulation. The normalized CFSE-proliferation index was between 2.1 and 3.0. Although there was no significant correlation between these three assays in the healthy controls, the SI value for &lt;10% [3H]-thymidine proliferation in those with T cell deficiency was compatible with CFSE- and Ki-67-stained lymphocyte percentages, and validated in patients with IL2RG, RAG1, and ZAP70 mutations. When calculating [3H]-thymidine &lt;10% of normal lymphocyte proliferation, the threshold of parallel controls was more reliable than previously established normal references.ConclusionThe large quantitative value of radioactive [3H]-thymidine was more easily recognizable than that for non-radioactive CFSE and Ki-67. Even though the correlation was not significant, those identified to have &lt;10% of normal proliferation by [3H]-thymidine could be consistently detected by CFSE and Ki-67, and consequently indicated for HSCT.