Analysis of choroidal thickness in juvenile systemic lupus erythematosus and its correlation with laboratory tests.

BACKGROUND: The aim of this study is to investigate the alterations of choroidal thickness (CT) in juvenile systemic lupus erythematosus (JSLE) using enhanced depth imaging optical coherence tomography (EDI-OCT). We also aimed to assess whether CT parameters correlated with systemic health status in JSLE patients. METHODS: JSLE patients and age- and sex-matched healthy subjects were recruited. A detailed ophthalmological examination was applied to all participants. CT measurements were acquired in the macular region using EDI-OCT. Moreover, a spectrum of laboratory tests was examined to evaluate the systemic conditions, and the Th1/Th2/Th17/Treg cytokine profiles in the peripheral blood were also analyzed in JSLE group. RESULTS: A total of 45 JSLE patients with no visual impairment and 50 healthy individuals were enrolled in the study. CT values in the macular region were decreased in JSLE patients when compared with healthy controls, even adjusting for age, axial length and refraction. There were no significant correlations between CT and cumulative dose of hydroxychloroquine or duration of hydroxychloroquine use (all P > 0.05). The average macular, temporal and subfoveal CT in JSLE group was negatively correlated with IL-6 and IL-10 (all P < 0.05), but had no significant correlations with other laboratory results (all P > 0.05). CONCLUSIONS: JSLE patients without ocular involvement may have significant variations in choroidal thickness at the macular area. Choroidal alterations might be associated with the systemic cytokine profiles in JSLE.

Size-segregated particle number concentrations and outpatient-department visits for pediatric respiratory diseases in Shanghai, China.

BACKGROUND: Few studies have simultaneously explored which size of particles has the greatest impact on the risk for pediatric asthma, bronchitis and upper respiratory tract infections (URTIs). OBJECTIVES: To investigate the short-term association between size-segregated particle number concentrations (PNCs) and outpatient-department visits (ODVs) for major pediatric respiratory diseases. METHODS: Daily counts of pediatric ODVs for asthma, bronchitis and URTIs were obtained from 66 hospitals in Shanghai, China, from 2016 to 2018. Pollutant effects were estimated using Poisson generalized additive models combined with polynomial distributed lag models. We also fitted co-pollutant cumulative effects models included six criteria air pollutants and conducted stratifying analyses by gender, age, season and geographic distances. RESULTS: We identified a total of 430,103 patients with asthma, 1,547,013 patients with bronchitis, and 2,155,738 patients with URTIs from the hospitals. Effect estimates increased with decreasing particle size. Ultrafine particle (UFP) and PNCs of 0.10-0.40 µm particles (PNC0.10-0.40) were associated with increased ODVs for asthma, bronchitis and URTIs at cumulative lags up to 3d. Associations tended to appear stable after adjusting for criteria air pollutants. At the cumulative lag 0-2d, each interquartile range increase in UFP was associated with increased ODVs due to asthma (relative risk 1.21, 95% CI: 1.07, 1.38), bronchitis (1.20, 95% CI: 1.07, 1.34) and URTI (1.17, 95% CI: 1.06, 1.30), whereas the associations for PNC0.10-0.40 remained significant but attenuated in magnitude. CONCLUSIONS: UFP may be a leading contributor to the adverse respiratory effects of particulate air pollution and the effects increased with decreasing particle size.

Evaluation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in children and adults.

OBJECTIVE: To evaluate the performance of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR-2019) classification criteria for systemic lupus erythematosus (SLE) compared with the ACR-1997 and Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) patients. METHODS: We conducted a retrospective study of SLE patients (221 children and 221 adults) and controls (214 children and 214 adults) with defined rheumatic diseases to establish each ACR-1997, SLICC-2012, and EULAR/ACR-2019 criterion fulfilled. Demographic, clinical, and laboratory features were evaluated through chart review. RESULTS: For cSLE, sensitivities of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria were 63.3%, 94.6%, and 98.2%, with specificities 99.5%, 98.6%, and 93.5%, respectively. For aSLE, sensitivities of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria were 72.9%, 96.8%, and 99.1%, with specificities 97.2%, 92.5%, and 90.2%, respectively. When including only ANA positive patients, receiver operating characteristics analysis demonstrated that the cutoff value for EULAR/ACR-2019 criteria in cSLE and aSLE patients was 13 (sensitivity, 92.2%; specificity, 93.1%) and 10 (sensitivity, 99.1%; specificity, 85.1%), respectively. Twelve cSLE patients and seven aSLE patients only met the EULAR/ACR-2019 criteria, among whom eleven and four cases had single organ involvement, respectively. CONCLUSION: The EULAR/ACR-2019 criteria showed similar sensitivity to cSLE and aSLE patients and was more sensitive than ACR-1997 and SLICC-2012 criteria, allowing earlier recognition of patients with single or major organ involvement. The adoption of a EULAR/ACR total score ≥ 13 in this study, instead of the initially proposed ≥ 10 points, could further improve the diagnostic performance of the EULAR/ACR-2019 criteria in cSLE. Key Points • Sensitivity of the EULAR/ACR-2019 criteria was high in both cSLE and aSLE patients. • The EULAR/ACR-2019 criteria allowed earlier recognition of patients with single or major organ damage. • The adoption of a EULAR/ACR total score ≥13 could further improve the diagnostic performance of the EULAR/ACR-2019 criteria in cSLE.

P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.

B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline novel or rare P2RY8 missense variants in lupus kindreds or the related antiphospholipid syndrome, including a "de novo" variant in a child with severe nephritis. All variants decreased protein expression, F-actin abundance, and GPCR-RhoA signaling, and those with stronger effects increased AKT and ERK activity and cell migration. Remarkably, P2RY8 was reduced in B cell subsets from some SLE patients lacking P2RY8 gene variants. Low P2RY8 correlated with lupus nephritis and increased age-associated B cells and plasma cells. By contrast, P2RY8 overexpression in cells and mice restrained plasma cell development and reinforced negative selection of DNA-reactive developing B cells. These findings uncover a role of P2RY8 in immunological tolerance and lupus pathogenesis.

Characteristics of childhood allergic diseases in outpatient and emergency departments in Shanghai, China, 2016-2018: a multicenter, retrospective study.

BACKGROUND: The prevalence of allergic diseases (ADs), such as asthma and allergic rhinitis (AR), is increasing worldwide in both adults and children. Although ADs are common and frequently coexist in outpatient care, city-level data regarding the characteristics of childhood AD remain limited in China. This study aimed to assess the profile and characteristics of ADs in the city of Shanghai. METHODS: A multicenter retrospective study was designed to collect routine administrative data from outpatient and emergency departments from 66 hospitals in Shanghai, China, from 2016 to 2018. Children with asthma, AR, allergic conjunctivitis (AC), and allergic skin diseases were investigated. Demographic characteristics, patients visit pattern, spectrum of diagnosis, and comorbidities were analyzed. RESULTS: A total of 2,376,150 outpatient and emergency visits for ADs were included in the period from 2016 to 2018. Allergic skin diseases accounted for 38.9%, followed by asthma (34.8%), AR (22.9%), and AC (3.3%), with a male predominance in all four diseases. Asthma and allergic skin diseases were most frequent in the 1 to < 4 years of age group, while AR and AC were more common in the 4 to < 7 years of age group. Asthma accounted for the greatest number of annual and emergency visits. The most frequent comorbidity of asthma was lower respiratory tract infection (LRTI) (49.3%), followed by AR (20.5%) and upper respiratory tract infection (14.1%). The most common comorbidities of AR were otitis media (23.4%), adenoid hypertrophy/obstructive sleep apnea (22.1%), followed by LRTI (12.1%), asthma (9.4%) and chronic pharyngitis (8.9%). CONCLUSIONS: Asthma and allergic skin diseases were the most common ADs in outpatient and emergency departments in the study period. Respiratory tract infection was the most common comorbidity of asthma in children. More attention should be devoted to the treatment of comorbidities to improve childhood AD outcomes with a better understanding of the characteristics of ADs in outpatient care.

Associations of fine particulate matter and constituents with pediatric emergency room visits for respiratory diseases in Shanghai, China.

BACKGROUND: Although ambient fine particulate matter (PM2.5) has been associated with adverse respiratory outcomes in children, few studies have examined PM2.5 constituents with respiratory diseases in children in China. OBJECTIVES: To investigate the associations of short-term exposure to PM2.5 and its constituents with pediatric emergency room visits (ERVs) for respiratory diseases in Shanghai, China. METHODS: We collected daily concentrations of PM2.5 and its constituents in urban Shanghai from January 1, 2016, to December 31, 2018. Daily pediatric ERVs for four major respiratory diseases, including upper respiratory tract infection, bronchitis, pneumonia, and asthma, were obtained from 66 hospitals in Shanghai during the same period. Associations of exposure to daily PM2.5 and constituents with respiratory ERVs were estimated using the over-dispersed generalized additive models. RESULT: Short-term exposure to PM2.5 and its constituents were associated with increased pediatric ERVs for respiratory diseases. Specifically, an interquartile range increase in the 3-day average PM2.5 level (31 µg/m3) was associated with 1.86% (95%CI: 0.52, 3.22), 1.53% (95%CI: 0.01, 3.08), 1.90% (95%CI: 0.30, 3.52), and 2.67% (95%CI: 0.70, 4.68) increase of upper respiratory tract infection, bronchitis, pneumonia, and asthma ERVs, respectively. As for PM2.5 constituents, we found organic carbon, ammonium, nitrate, selenium, and zinc were associated with higher risk of respiratory ERVs in the single constituent and the constituent-PM2.5 models. CONCLUSION: Short-term exposure to PM2.5 was associated with increased pediatric ERVs for respiratory diseases. Constituents related to anthropogenic combustion and traffic might be the dominant contributors of the observed associations.

Ultrafine particulate air pollution and pediatric emergency-department visits for main respiratory diseases in Shanghai, China.

BACKGROUND: Few studies have explored the short-term effects of ultrafine particles (UFPs, particles < 0.1 µm) air pollution on the exacerbations of pediatric respiratory diseases. OBJECTIVES: We aimed to evaluate short-term association between UFP and emergency-department visits (EDVs) for main pediatric respiratory diseases. METHODS: We collected daily data on UFP and pediatric EDVs for main respiratory diseases [asthma, pneumonia, bronchitis and upper respiratory tract infections (URTI)] from 66 hospitals in Shanghai, China from 2016 to 2018. Generalized additive models combined with polynomial distributed lag models were applied to explore the associations between UFP level and pediatric EDVs for respiratory diseases. We fitted two-pollutant models with criteria air pollutants and performed stratified analyses by gender and age. RESULTS: UFP was associated with increased EDVs for all respiratory diseases in cumulative lags up to 2 d and 3 d. The greatest risk was found at cumulative lags (0-2 d) for all respiratory diseases. At cumulative lags (0-2 d), an interquartile range increase in concentrations of UFP (1800 particles/cm3) was associated with relative risks of EDVs due to asthma [1.35, 95% confidence interval (CI): 1.14-1.59], pneumonia (1.20, 95% CI: 1.04-1.38), bronchitis (1.17, 95% CI: 1.03-1.33) and URTI (1.14, 95% CI: 1.02-1.28). These associations were almost unchanged when controlling for criteria air pollutants, and there was no threshold below which the associations were not present. There were stronger associations in children aged 0-13 years. CONCLUSIONS: Short-term exposure to UFP may independently increase the risks of EDVs for asthma, pneumonia, bronchitis and URTI exacerbations among children.

Associations of short-term exposure to air pollution and emergency department visits for pediatric asthma in Shanghai, China.

There is limited evidence regarding the relationship between air pollution and pediatric asthma in developing countries. This study aimed to investigate the association between short-term exposure to ambient air pollutants and pediatric asthma emergency department (ED) visits in Shanghai, China. We collected data on six criteria air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and daily ED visits for pediatric asthma patients from 66 hospitals in Shanghai from 2016 to 2018. The generalized additive model combined with polynomial distributed lag model was applied to explore the associations. We fitted two-pollutant models and stratified the analyses by sex, age, and season. In total, we identified 108,817 emergency department visits for pediatric asthma. A 10 µg/m3 increase in the concentrations of PM2.5, NO2, SO2, and O3 was significantly associated with increased risks of pediatric asthma ED visits, with relative risk of pediatric asthma of 1.011 [95% confidence interval (CI): 1.002, 1.021], 1.030 (95%CI: 1.017, 1.043), 1.106 (95%CI: 1.041, 1.174), and 1.009 (95%CI: 1.001, 1.017), respectively. The associations of NO2 remained robust in the two-pollutant models. There were stronger associations for older children (6-18 years) and in warm seasons. The concentration-response curves for pediatric asthma and PM2.5, NO2, SO2, and O3 were steeper at lower and moderate concentrations but became flatter at higher concentrations. This analysis provided evidence that short-term exposure to air pollutants (PM2.5, NO2, SO2, and O3) could increase the risk of asthma exacerbations among children, and health benefits would be gained from improved air quality.

Temperature changes between neighboring days and childhood asthma: a seasonal analysis in Shanghai, China.

Few evidences are available about the impact of temperature variation on childhood asthma in different seasons. This study aimed to assess the influence of temperature changes between neighboring days (TCN) on the exacerbation of asthma among children. Daily outpatient visits for childhood asthma (DOVCA) were collected from 17 main hospitals in Shanghai, China, from 2016 to 2018. A quasi-Poisson regression combined with distributed lagged nonlinear models was employed to estimate the association between TCN and asthma visits in cool or warm seasons, after controlling for short- and long-term trends, day of week, holidays, daily mean temperature, daily mean relative humidity, and air pollutants. The TCN varied from - 9.6 to 6.7 °C. The relationship between TCN and DOVCA greatly varied by season. In warm seasons, positive TCN (temperature rise) was associated with higher risks of asthma outpatient visits and negative TCN (temperature drop) was associated with lower risks; the associations were present on lag 1 day and lasted for 2 weeks; the cumulative relative risk of childhood asthma over 0 to 14 days was 1.98 (95% confidence interval: 1.42, 2.76) and 0.31 (95% confidence intervals: 0.21, 0.44) comparing a TCN of 2.5 °C (5th percentile) and - 3.2 °C (95th percentile) with 0 °C, respectively. In cool seasons, neither negative nor positive TCN showed significant risks. In conclusion, temperature rise might increase the risk of childhood asthma exacerbation and temperature drop might decrease the risks in warm seasons. There were no statistically significant influences in cool seasons.

Lignin catabolic pathways reveal unique characteristics of dye-decolorizing peroxidases in Pseudomonas putida.

Lignin is one of the largest carbon reservoirs in the environment, playing an important role in the global carbon cycle. However, lignin degradation in bacteria, especially non-model organisms, has not been well characterized either enzymatically or genetically. Here, a lignin-degrading bacterial strain, Pseudomonas putida A514, was used as the research model. Genomic and proteomic analyses suggested that two B subfamily dye-decolorizing peroxidases (DypBs) were prominent in lignin depolymerization, while the classic O2 -dependent ring cleavage strategy was utilized in central pathways to catabolize lignin-derived aromatic compounds that were funnelled by peripheral pathways. These enzymes, together with a range of transporters, sequential and expression-dose dependent regulation and stress response systems coordinated for lignin metabolism. Catalytic assays indicated these DypBs show unique Mn2+ independent lignin depolymerization activity, while Mn2+ oxidation activity is absent. Furthermore, a high synergy between DypB enzymes and A514 cells was observed to promote cell growth (5 × 1012 cfus/ml) and lignin degradation (27%). This suggested DypBs are competitive lignin biocatalysts and pinpointed limited extracellular secretion capacity as the rate-limiting factor in bacterial lignin degradation. DypB production was, therefore, optimized in recombinant strains and a 14,141-fold increase in DypB activity (56,565 U/l) was achieved, providing novel insights for lignin bioconversion.

Melatonin Enhances Proliferation and Modulates Differentiation of Neural Stem Cells Via Autophagy in Hyperglycemia.

Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes. Moreover, Mel enhanced NSCs proliferation and self-renewal in HG with decreasing autophagy and activated mTOR signaling. Consistently, inhibition of autophagy by 3-Methyladenine (3-Ma) could assist Mel effects above, and induction of autophagy by Rapamycin (Rapa) could diminish Mel effects. Remarkably, HG induced premature differentiation of NSCs into neurons (Map2 positive cells) and astrocytes (GFAP positive cells). Furthermore, Mel diminished HG-induced premature differentiation and assisted NSCs in HG differentiation as that in normal condition. Coincidentally, inhibiting of NSCs autophagy by 3-Ma assisted Mel to modulate differentiation. However, increasing NSCs autophagy by Rapa disturbed the Mel effects and retarded NSCs differentiation. These findings suggested that Mel supplementation could contribute to mimicking normal NSCs proliferation and differentiation in fetal central nervous system by inhibiting autophagy in the context of gestational diabetes. Stem Cells 2019;37:504-515.

Identification of differentially expressed genes associated with asthma in children based on the bioanalysis of the regulatory network.

Asthma, the most common chronic respiratory tract disease in children, is characterized by allergy, recurring airway obstruction and bronchospasm. The aim of the present study was to screen critical differentially expressed genes (DEGs) involved in asthma in children. Gene expression in different tissues was compared between asthmatic children and healthy control subjects in order to identify DEGs associated with asthma. Protein­protein interaction (PPI) networks were constructed for the DEGs and weighted gene co­expression network analysis methods were used to further determine the functional modules associated with DEGs in different tissue samples. In addition, the gene co­expression network was constructed. Gene Ontology function analysis and pathway analysis were conducted to identify critical DEGs. The results identified numerous DEGs from the different tissue samples, including 1,662 DEGs from nasal­epithelium tissue samples, 572 DEGs from peripheral blood (PB) samples and 146 DEGs from PB mononuclear cells samples. In the PPI network, F­box only protein 6 (FBXO6), histone deacetylase 1 (HDAC1) and amyloid ß precursor protein (APP) were hub genes and served an important role in the process of asthma. In addition, proliferating cell nuclear antigen (PCNA), integrin α­4 (ITGA4), catenin α­1 (CTNNA1), nuclear factor­κB1 (NF­κB1) and mechanistic target of rapamycin (MTOR) may be critical DEGs involved in the progression of asthma in children. These results suggested that FBXO6, HDAC1 and APP may interact with PCNA, ITGA4, CTNNA1, NF­κB1 and mTOR in the progression of asthma in children.

DNA induction of MDM2 promotes proliferation of human renal mesangial cells and alters peripheral B cells subsets in pediatric systemic lupus erythematosus.

The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC). We also proved that elevated apoptotic and necrotic CD4+T cells were the main cause for increased plasma levels of cfDNA in pSLE. Additionally, upon DNA transfection MDM2 increased while P53 and P21 decreased in human renal mesangial cells (HRMC), with concomitant increase in proliferation rate and proportion of cells in S phase, as demonstrated by cell proliferation assay and cell cycle analysis. However, MDM2 inhibition reversed the trend. Furthermore, percentage of switched memory B cells decreased and proportion of double negative B cells increased upon blockage of MDM2 in PBMC. In summary, our study provided the first evidence that DNA induction of MDM2 promotes proliferation of HRMC and alters peripheral B cells subsets in pSLE. Thus our study has not only elucidated the pathogenesis of MDM2 in pediatric LN but also provided a novel target for drug development. In conclusion, our data suggested that apoptosis, cfDNA and MDM2 could form a pathological axis in SLE, especially in pSLE.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

BACKGROUND: Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). METHODS: The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1ß, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. RESULTS: Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. CONCLUSIONS: Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Changes of Treg and Th17 cells as well as cytokines in children with acute bronchitis.

The present study aimed to investigate changes of T-regulatory (Treg) and T-helper (Th)17 cells as well as cytokines in peripheral blood of children with acute bronchitis, and to explore the roles of these cells in the pathogenesis of acute bronchitis. A total of 126 children who had presented at Renji Hospital (Shanghai, China) with acute bronchitis were selected as the observation group and 30 healthy children were selected as the control group. Th17/Tregs in the peripheral blood of the children of the observation group and the control group was detected by flow cytometry. The levels of cytokines interleukin (IL)-17, IL-22, IL-10 and transforming growth factor (TGF)-ß in peripheral blood serum were detected by ELISA. Compared with those in the control group, Treg cells, the Treg/Th17 ratio as well as serum IL-10 and TGF-ß levels were significantly decreased in the observation group (P<0.05), while Th17 cells as well as serum levels of IL-17 and IL-22 were significantly increased (P<0.05). In conclusion, Treg/Th17 and the expression of associated cytokines lost their balance in children with acute bronchitis, suggesting that Treg and Th17 cells as well as their cytokines may be involved in the pathogenesis of acute bronchitis. It may be of certain guiding significance to detect Treg/Th17 and levels of serum cytokines in peripheral blood for clinical treatment.

Atopy in children with juvenile systemic lupus erythematosus is associated with severe disease.

The influence of co-existing atopy on the prognosis of juvenile systemic lupus erythematosus (JSLE) was assessed in this study. Patients diagnosed with JSLE between October 2005 and April 2016 were enrolled in a prospective study and followed up for 2 years. Management of patients was evaluated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score and laboratory variables. Eighty JSLE patients were enrolled at diagnosis and divided into those with (n = 35) and without (n = 45) atopy. When compared with the non-atopic group, atopic patients showed higher SLEDAI-2K score at disease onset (16.09 vs. 11.18), higher erythrocyte sedimentation rate (52.89 vs. 38.27 mm/h), higher percentage of total B-cells (25.85 vs. 19.51%), lower percentage (7.26 vs. 9.03%) and cytotoxicity (9.92 vs. 11.32%) of natural killer cells, and lower complement C3 (0.51 vs. 0.69 g/L) (all p<0.05). At 1, 3, 6, 12, 18, and 24 months, JSLE patients with atopy reached higher SLEDAI-2K score and lower ΔSLEDAI-2K improvement rate (at 1 month, 8.34 vs. 4.71 and 43.63 vs. 57.95%, respectively; at 3 months, 8.57 vs. 2.62 and 48.39 vs. 75.10%, respectively; at 6 months, 6.91 vs. 2.38 and 53.59 vs. 77.26%, respectively; at 12 months, 4.71 vs. 1.80 and 69.54 vs. 84.10%, respectively; at 18 months, 4.66 vs. 2.02 and 68.14 vs. 82.93%, respectively; at 24 months, 8.57 vs. 2.62 and 70.00 vs. 81.88%, respectively; all p<0.05). During the 24 months of follow-up, the total number of disease flares was higher in JSLE patients with co-existing atopy (3.77 vs. 1.51, p<0.05), and the atopic group needed much more time to reach the stable condition of the disease (6.88 vs. 4.65 months, p<0.05). JSLE patients combined with co-existing atopy had more severe disease at diagnosis and poorer outcomes than JSLE patients without atopy.

[Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus].

OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups. RESULTS: The AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.

Identification of potential peripheral blood diagnostic biomarkers for patients with juvenile idiopathic arthritis by bioinformatics analysis.

Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming children health. However, there is still lack of effective biomarkers for diagnosis JIA at early onset. We aim to construct a classification model to predict JIA disease. The peripheral blood gene expression profile data of JIA were downloaded from GEO database. We compared and analyzed differentially expressed genes (DEGs) between different JIA samples through Pearson's correlation coefficient method and unsupervised clustering analysis. Diagnostic model were constructed based on the deviation pathway through bioinformatics method. Eighteen specific correlated DEGs were obtained, but the correlations altered in different disease states. Although most JIA and control samples were clustered by unsupervised clustering analysis, respectively, a few JIA samples could not be clustered well. Four co-expression networks were next constructed with gene connections dynamically altered under variable conditions. Eight signaling pathways were significantly enriched including B/T cell receptor, ErbB and MAPK signaling pathways. The deviation scores of pathways were calculated. Applying these eight signaling pathways as feature to construct a classification model could predict JIA disease with high accuracies. Our data provide some light into pathogenic mechanism of JIA, the specific gene sets and the related signaling pathways may be potential biomarkers for diagnosis or therapeutic targets of JIA.