Evaluation of Disease Activity of Systemic Lupus Erythematosus by D-dimer Combined with Red Blood Cell Distribution Width.

BACKGROUND: To investigate the value of D-dimer combined with red blood cell distribution width (RDW) in evaluating the disease activity of systemic lupus erythematosus (SLE). METHODS: A total of 105 SLE patients confirmed in our hospital from July 2018 to September 2020 were collected as the SLE group, and 60 healthy persons matched in age and gender during the same period were collected as the control group. According to the SLEDAI score, SLE patients were divided into SLE active group and SLE inactive group, and RDW and D-Dimer levels were detected. RESULTS: The level of RDW in the SLE active group [14.8 (13.4, 16.8)] was significantly higher than that in the SLE inactive group [13.4 (12.6, 14.37)] and control group [12.3 (12, 12.7)], with statistically significant differences (p < 0.05). The D-dimer level in the SLE active group was 1.36 (0.9, 2.25) mg/L, which was significantly higher than that in SLE inactive group [0.34 (0.22, 0.52)] mg/L and control group [0.15 (0.08, 0.19)] mg/L, with statistically significant differences (p < 0.05). Both RDW and D-dimer were positively correlated with the SLEDAI score (r = 0.393, p = 0.000), (r = 0.483, p = 0.000). The results of receiver operating characteristic curve showed that the area under the curve of RDW and D-Dimer alone was 0.875 and 0.954, respectively, while the area under the curve of RDW combined with D-Dimer was the largest, 0.984. CONCLUSIONS: The levels of RDW and D-dimer are closely related to the disease activity of SLE patients, and RDW combined with D-dimer is more valuable in assessing the disease activity of SLE patients.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

Gene Expression Analysis in Three Posttraumatic Stress Disorder Cohorts Implicates Inflammation and Innate Immunity Pathways and Uncovers Shared Genetic Risk With Major Depressive Disorder.

Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop following exposure to traumatic events. The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has collected over 20,000 multi-ethnic PTSD cases and controls and has identified both genetic and epigenetic factors associated with PTSD risk. To further investigate biological correlates of PTSD risk, we examined three PGC-PTSD cohorts comprising 977 subjects to identify differentially expressed genes among PTSD cases and controls. Whole blood gene expression was quantified with the HumanHT-12 v4 Expression BeadChip for 726 OEF/OIF veterans from the Veterans Affairs (VA) Mental Illness Research Education and Clinical Center (MIRECC), 155 samples from the Injury and Traumatic Stress (INTRuST) Clinical Consortium, and 96 Australian Vietnam War veterans. Differential gene expression analysis was performed in each cohort separately followed by meta-analysis. In the largest cohort, we performed co-expression analysis to identify modules of genes that are associated with PTSD and MDD. We then conducted expression quantitative trait loci (eQTL) analysis and assessed the presence of eQTL interactions involving PTSD and major depressive disorder (MDD). Finally, we utilized PTSD and MDD GWAS summary statistics to identify regions that colocalize with eQTLs. Although not surpassing correction for multiple testing, the most differentially expressed genes in meta-analysis were interleukin-1 beta (IL1B), a pro-inflammatory cytokine previously associated with PTSD, and integrin-linked kinase (ILK), which is highly expressed in brain and can rescue dysregulated hippocampal neurogenesis and memory deficits. Pathway analysis revealed enrichment of toll-like receptor (TLR) and interleukin-1 receptor genes, which are integral to cellular innate immune response. Co-expression analysis identified four modules of genes associated with PTSD, two of which are also associated with MDD, demonstrating common biological pathways underlying the two conditions. Lastly, we identified four genes (UBA7, HLA-F, HSPA1B, and RERE) with high probability of a shared causal eQTL variant with PTSD and/or MDD GWAS variants, thereby providing a potential mechanism by which the GWAS variant contributes to disease risk. In summary, we provide additional evidence for genes and pathways previously reported and identified plausible novel candidates for PTSD. These data provide further insight into genetic factors and pathways involved in PTSD, as well as potential regions of pleiotropy between PTSD and MDD.

AQP1 and SLC4A10 as candidate genes for primary open-angle glaucoma.

PURPOSE: Recent evidence supports the role of reduced cerebrospinal fluid (CSF) pressure in the pathogenesis of primary open-angle glaucoma (POAG). We investigated the association of variants in two candidate genes that are important in CSF production, aquaporin 1 (AQP1) and solute carrier family 4, sodium bicarbonate transporter, member 10 (SLC4A10), with POAG in the Caucasian population. METHODS: POAG subjects (n=382) met the criteria of glaucomatous optic neuropathy with consistent visual field loss. Intraocular pressure was not used as an inclusion criterion. Control subjects (n=363) did not meet any of the inclusion criteria and had no family history of glaucoma. Eleven tagging single nucleotide polymorphisms (SNPs) for AQP1 and SLC4A10 were genotyped in the POAG and control subjects, using allelic discrimination assays. Genotype frequencies were compared between the POAG and control subjects, using logistic regression adjusted for gender. RESULTS: There was no statistically significant difference in genotype frequencies between POAG and control subjects for any of the tested SNPs in AQP1 and SLC4A10 (p>0.05). CONCLUSIONS: There was no association between common sequence variants in the AQP1 or SLC4A10 genes and POAG in the Caucasian population. This is the first study to investigate the association between these two candidate genes and increased risk for POAG.

CCL22 recruits CD4-positive CD25-positive regulatory T cells into malignant pleural effusion.

PURPOSE: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory T cells infiltrating into the pleural space. EXPERIMENTAL DESIGN: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed. RESULTS: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space. CONCLUSIONS: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.

CCL22 is involved in the recruitment of CD4+CD25 high T cells into tuberculous pleural effusions.

BACKGROUND AND OBJECTIVE: CD4(+)CD25(high) regulatory T cells are increased in tuberculous pleural effusions (TPE). However, the mechanism by which CD4(+)CD25(high) T cells infiltrate into the pleural cavity is unknown. The aim of this study was to investigate whether the chemokines CCL22 and CCL17 are present in TPE, and the chemoattractant activity of these chemokines for infiltration of CD4(+)CD25(high) T cells into the pleural space. METHODS: The concentrations of CCL22 and CCL17 were measured in pleural effusions from 33 patients with tuberculous pleurisy, 21 patients with pleural bacterial infections and 18 patients with transudative pleural effusions. T lymphocyte subsets in pleural effusions were assessed by flow cytometry. Pleural effusion cells were analysed for the expression of CCL22. The chemoattractant activity of CCL22 for CD4(+)CD25(high) T cells was assessed in vitro. RESULTS: The frequency of CD4(+)CD25(high) T cells was significantly higher in TPE than in blood. High concentrations of CCL22 were detected in tuberculous effusions, but not in bacterial effusions or transudates. Macrophages and T cells in TPE expressed CCL22. Tuberculous pleural fluid was chemotactic for CD4(+)CD25(high) T cells in vitro, and anti-CCL22 antibody partly inhibited this chemotactic activity. CONCLUSIONS: CCL22 appeared to be increased in TPE compared with bacterial pleural effusions or transudates. CCL22 may be responsible for the infiltration of CD4(+)CD25(high) T cells into the pleural space of patients with tuberculous pleurisy.

An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci.

BACKGROUND: Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD). METHODS: In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72). RESULTS: The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 × 10-6, padj = 0.042). CONCLUSIONS: The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.

Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis.

BACKGROUND: Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a meta-analysis to determine the accuracy of ADA measurements in the diagnosis of tuberculous pleurisy. METHODS: After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of ADA concentration in the diagnosis of pleural effusion were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS: Sixty-three studies met our inclusion criteria. The summary estimates for ADA in the diagnosis of tuberculous pleurisy in the studies included were sensitivity 0.92 (95% confidence interval 0.90-0.93), specificity 0.90 (95% confidence interval 0.89-0.91), positive likelihood ratio 9.03 (95% confidence interval 7.19-11.35), negative likelihood ratio 0.10 (95% confidence interval 0.07-0.14), and diagnostic odds ratio 110.08 (95% confidence interval 69.96-173.20). CONCLUSIONS: ADA determination is a relative sensitive and specific test for the diagnosis of tuberculous pleurisy. Measurement of ADA in pleural effusion is thus likely to be a useful diagnostic tool for tuberculous pleurisy. The results of ADA assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Diagnostic value of carcinoembryonic antigen in malignant pleural effusion: a meta-analysis.

BACKGROUND AND OBJECTIVE: Conventional tests are not always helpful in making a diagnosis of malignant pleural effusion (MPE). Many studies have investigated the utility of pleural carcinoembryonic antigen (CEA) in the early diagnosis of MPE. The present meta-analysis determined the accuracy of CEA measurement in the diagnosis of MPE. METHODS: A systematic review of English language studies was conducted and data on the accuracy of pleural CEA concentrations in the diagnosis of MPE were pooled using random effects models. Receiver operating characteristic curves were used to summarize the overall test performance. RESULTS: Forty-five studies met the inclusion criteria for the meta-analysis. The summary estimates for CEA in the diagnosis of MPE were: sensitivity 0.54 (95% CI: 0.52-0.55), specificity 0.94 (95% CI: 0.93-0.95), positive likelihood ratio 9.52 (95% CI: 6.97-13.01), negative likelihood ratio 0.49 (95% CI: 0.44-0.54) and diagnostic odds ratio 22.5 (95% CI: 15.6-32.5). Analysis of a subset of 11 studies which examined the value of pleural CEA in ruling out a diagnosis of malignant mesothelioma found that the sensitivity and specificity of a CEA level exceeding cut-off values were 0.97 (95% CI: 0.93-0.99) and 0.60 (95% CI: 0.55-0.65), respectively. CONCLUSIONS: Measurement of pleural CEA is likely to be a useful diagnostic tool for confirming MPE, and is also helpful in the differential diagnosis between malignant pleural mesothelioma and metastatic lung cancer. The results of CEA assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Expression of soluble triggering receptor expression on myeloid cells-1 in pleural effusion.

BACKGROUND: Triggering receptors expressed on myeloid cells (TREM) proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 (sTREM-1) in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations. METHODS: Pleural fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate). The concentrations of sTREM-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA). RESULTS: The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups (all P < 0.001). An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-alpha and IL-1beta. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia. CONCLUSIONS: Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.

CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion.

BACKGROUND: Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens. This study was conducted to analyze whether the CD4+CD25+ regulatory T cells exist and function normally in tuberculous pleural effusion. METHODS: The percentages of CD4+CD25+ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry. The expression of forkhead transcription factor Foxp3 was also examined. CD4+CD25+ and CD4+CD25(-) T cells from pleural effusion and blood were isolated, and were cultured to observe the effects of CD4+CD25+ T cells on proliferation response of CD4+CD25(-) T cells in vitro. RESULTS: There were increased numbers of CD4+CD25+ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects, and these cells demonstrated a constitutive high-level expression of Foxp3. Moreover, CD4+CD25+ T cells mediated potent inhibition of proliferation response of CD4+CD25(-) T cells. CONCLUSION: The increased CD4+CD25+ T cells in tuberculous pleural effusion express a high level of Foxp3 transcription factor, while potently suppressing the proliferation of CD4+CD25(-) T cells.

Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis.

BACKGROUND: Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-gamma measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-gamma measurements in the diagnosis of tuberculous pleurisy. METHODS: After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-gamma concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS: Twenty-two studies met our inclusion criteria. The summary estimates for IFN-gamma in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2). CONCLUSIONS: IFN-gamma determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-gamma levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-gamma assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Increase in concentration of soluble CD86 after segmental allergen challenge in patients with allergic asthma.

STUDY OBJECTIVE: To investigate the effects of segmental allergen challenge on the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic asthma. METHODS: BAL fluid and peripheral blood were collected at baseline, 24 h after segmental saline solution or allergen challenge by fiberoptic bronchoscopy and venepuncture, respectively, from 10 patients with allergic asthma. Total and differential cell counts in BAL fluid were performed, and sCD86 levels in both BAL fluid and serum were measured by enzyme-linked immunosorbent assay. RESULTS: In allergic asthmatics, there was no significant increase in BAL sCD86 concentrations after saline solution challenge (median, 2.0 IU/L; 25th to 75th percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2 IU/L; 25th to 75th percentiles, 0 to 3.6 IU/mL; p = 0.735); however, sCD86 concentrations were significantly elevated after allergen challenge (median, 8.1 IU/L; 25th to 75th percentiles, 4.4 to 17.0 IU/mL; p < 0.001). The concentrations of sCD86 in BAL fluid after allergen challenge exceeded levels that could be accounted for passive transudation from the circulation, based on the magnitude of increases in BAL albumin concentrations. CONCLUSIONS: These data indicate that allergen challenge results in a significant local accumulation of sCD86 within the airways, and that the local release of sCD86 may play a role in allergen-induced inflammatory processes in the asthmatic airways.

[Determination and significance of interleukin-16 in tuberculous and malignant pleural effusion].

OBJECTIVE: Interleukin-16 (IL-16) is a chemoattractant of CD4+ lymphocytes, and it has been implicated in the pathogenesis of various inflammatory diseases. The aim of the present study was to measure IL-16 in pleural effusions caused by tuberculosis and malignancy and its relationship with cell and differential counts as well as lymphocyte subsets. METHODS: Pleural effusion and venous blood samples were collected from 32 patients with tuberculous pleuritis and 30 lung cancer patients with malignant effusion. Analysis of pleural effusion for total leukocytes and cell differentials of leukocytes was performed. Three-color flow cytometry was performed to determine T lymphocyte subsets in cell pellets of pleural effusion. The concentration of IL-16 in cell-free supernatants of pleural effusion and sera was measured by a sandwich enzyme-linked immunosorbent assay. RESULTS: In all the studied patients, the level of IL-16 was significantly higher in pleural effusion than in serum. The levels of IL-16 were significantly higher in tuberculous than in malignant effusions. In pleural effusion, positive correlations were found between the IL-16 levels and total cell counts, lymphocytes, CD3+ T cells, as well as CD4+ T cells. CONCLUSIONS: Compared to malignant pleural effusion, IL-16 appeared to be increased in tuberculous pleural effusion. The pleural effusion IL-16 levels were positively related to the numbers of CD4+ T cells, suggesting that IL-16 might be capable of inducing CD4+ T cell infiltration into pleural space.

[CD4+CD25+ T lymphocytes in peripheral blood from patients with asthma].

OBJECTIVE: To explore whether regulatory CD(4)(+)CD(25)(+) cells exist in patients with atopic asthma. METHODS: The numbers of peripheral blood CD(4)(+)CD(25)(+) cells in peripheral blood of atopic asthmatics and healthy nonatopic subjects were determined using flow cytometry. CD(4)(+)CD(25)(+) and CD(4)(+)CD(25)(-) cells from atopic asthmatics and normal donors were isolated, and were cultured to observe the effects of CD(4)(+)CD(25)(+) cells on proliferation response as well as Th1/Th2 cytokine production of CD(4)(+)CD(25)(-) cells in vitro. RESULTS: A significant increase in CD(4)(+)CD(25)(+) cell numbers was shown in atopic asthmatic patients during acute exacerbation [(14.9 +/- 1.8)%, P < 0.01], but not in patients with stable asthma [(11.8 +/- 0.7)%] and normal subjects [(11.2 +/- 0.8)%, P > 0.05]. The mean inhibition values of the proliferation response of CD(4)(+)CD(25)(-) cells by CD(4)(+)CD(25)(+) cells from normal controls [(72 +/- 8)%] and asthmatics [(74 +/- 9)%] were similar (P > 0.05). There was no difference in inhibitory effects on both Th1 and Th2 cytokine production of CD(4)(+)CD(25)(-) cells by CD(4)(+)CD(25)(+) cells in the two groups. CONCLUSION: Although CD(4)(+)CD(25)(+) cells increase in atopic asthma during exacerbation, these regulatory T cells appear to function normally with regard to their suppressive activities.

Effects of antigen presentation of eosinophils on lung Th1/Th2 imbalance.

BACKGROUND: Antigen-loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2-type cytokine production in the draining lymph nodes. The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues. METHODS: Airway EOSs were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these EOSs were then cocultured with CD4+ cells isolated from sensitized mice in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines. RESULTS: Airway EOSs functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate lung CD4+ lymphocytes to produce interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma, production during the in vitro culture that was also CD80- and CD86-dependent. CONCLUSION: EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells in the lungs.

A SAGE study of apolipoprotein E3/3, E3/4 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.

APOE4 allele is a major risk factor for late-onset Alzheimer disease (AD). The mechanism of action of APOE in AD remains unclear. To study the effects of APOE alleles on gene expression in AD, we have analyzed the gene transcription patterns of human hippocampus from APOE3/3, APOE3/4, APOE4/4 AD patients and normal control using Serial Analysis of Gene Expression (SAGE). Using SAGE, we found gene expression patterns in hippocampus of APOE3/4 and APOE4/4 AD patients differ substantially from those of APOE3/3 AD patients. APOE3/4 and APOE4/4 allele expression may activate similar genes or gene pools with associated functions. APOE4 AD alleles activate multiple tumor suppressors, tumor inducers and negative regulator of cell growth or repressors that may lead to increased cell arrest, senescence and apoptosis. In contrast, there is decreased expression of large clusters of genes associated with synaptic plasticity, synaptic vesicle docking and fusing and axonal/neuronal outgrowth. In addition, reduction of neurotransmitter receptors and Ca2+ homeostasis, disruption of multiple signal transduction pathways, loss of cell protection, and perhaps most notably, mitochondrial oxidative phosphorylation/energy metabolism are associated with APOE3/4 and APOE4/4 AD alleles. These findings may help define the mechanisms that APOE4 contribute that increase risk for AD and identify new candidate genes conferring susceptibility to AD.

Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.

Apolipoprotein E4 (APOE4) allele is a major risk factor for late-onset familial and sporadic Alzheimer disease (AD). The mechanism of action of APOE in the etiology of AD remains unclear. Using gene expression (microarray) analysis of human hippocampus from APOE3/3 AD and APOE4/4 AD cases, we found different gene transcription patterns between APOE4/4 and APOE3/3 AD cases. The expression of APOE4/4 alleles, in comparison to APOE3/3, is associated with upregulation of multiple gene transcripts encoding cell growth suppresser or arrest, signal transduction, myelinogenesis, cell adhesion and migration, heavy metal metabolism and detoxification. Whereas the APOE4 gene expression is associated with downregulation of gene transcripts involved in mitochondrial oxidative phosphorylation and energy metabolism, synaptic vesicle docking and fusing, and synaptic plasticity compared to APOE3. These mechanisms may contribute increased risk for AD and for cognitive dysfunction in AD patients who carry the APOE4 allele(s).

Effects of allergen inhalation and oral glucocorticoid on concentrations of serum-soluble CD86 in allergic asthmatics.

The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum soluble CD86 in patients with allergic asthma. Our results showed that the serum soluble CD86 concentrations in the dual responder group increased from 491.8 +/- 15.4 IU/ml before allergen inhalation to 603.8 +/- 19.3 IU/ml 24 h after allergen inhalation. In the isolated early responders, there was no significant increase in serum soluble CD86 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum soluble CD86 concentrations after 2 weeks of glucocorticoid therapy (448.3 +/- 15.1 IU/ml) compared with baseline values (532.7 +/- 12.3 IU/ml), whereas there was no significant difference in the placebo group. This study has demonstrated that serum soluble CD86 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCD86 concentrations were downregulated by prednisolone therapy.