Project description:Despite the increasing number of patients suffering from tick-borne diseases, including tick-borne encephalitis (TBE) and Lyme disease, the mechanisms of development of these diseases and their effects on human body are still unknown. Moreover, the increasing number of cases of co-infections of these diseases additionally hampers the correct diagnosis and the application of effective therapy. Therefore, the aim of this study was to evaluate the changes in proteomic profile of human plasma induced by the development of TBE and to compare it with changes in TBE patients co-infected with other tick-borne pathogens. The results obtained by proteomic analysis using nanoLC-QExactive/MS showed that the most highly elevated groups of proteins in the plasma of TBE patients with co-infection were involved in the pro-inflammatory response and protein degradation, while the antioxidant proteins and factors responsible for protein biosynthesis were mainly down regulated. The main proteins, which expression differentiated patients with TBE from co-infected patients, such as AP-1, fumarylacetoacetase, serpin, annexin, or carbonic anhydrase 2, are involved in TBE virulence or antibacterial responses. These results were accompanied by the enhanced GSH- and 4-HNE-protein adducts formation, observed in TBE and co-infected patients on higher level than in the case of only TBE patients. In conclusion, the differences in the proteomic profiles between patients with TBE and co-infected indicate that the mechanisms of development of these diseases are diverse and, consequently, require different treatment, what is particularly important for further research, including the development of novel diagnostics tools.
Project description:Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. To date, chronic Dengue infections have not been previously reported. While investigating the etiology of central nervous system (CNS) disease in a patient presenting with progressive dementia, we elucidated a chronic dengue infection within the CNS. Comprehensive viral immune responses in both serum and cerebrospinal fluid (CSF) were profiled by a phage-display assay (VirScan). Enrichment of Dengue viral antibodies were detected in the CSF as compared to the serum. No virus was detected in serum or CSF, but post-mortem analysis confirmed Dengue virus in the brain by quantitative polymerase chain reaction (PCR), immunohistochemistry, RNAscope and sequencing. Dengue virus was detectable by PCR and sequencing from brain biopsy tissue collected 33 months ante-mortem, confirming a chronic infection. Comprehensive antibody profiling assays can aid in the diagnosis of encephalitis of unknown etiologies. Our findings suggest that Dengue virus infections may persist in the CNS and should be considered in patients with progressive dementia in endemic regions or with relevant travel history.
Project description:Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a nervous autoimmune disorder discovered in the recent more than fifteen years. To understand potential involvement of epigenetic mechanisms in pathogenesis of anti-NMDAR encephalitis, we initiated a study to compare the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNA (mRNAs) in patients of anti-NMDAR encephalitis and healthy controls. Methods: 11 patients who were diagnosed with anti-NMDAR encephalitis were enrolled in our observational studies. Total RNA was extracted from patients’ plasma and the expression levels of lncRNAs and mRNAswere determined. Differential expression analysis via RNA sequencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as a co-expression network of lncRNA-mRNA were performed in 5 patients and 5 healthy controls to evaluate potential the changes in expression patterns. The expression levels of certain lncRNAs and mRNAs were further validated in 11patients and 11 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). Results: It was found that a total of 83 lncRNAs and 2345 mRNAs were differentially expressed in five patients with anti-NMDAR encephalitis compared with five healthy controls. Of those lncRNAs, 63 were upregulated and 20 downregulated, while 1509 mRNAs were upregulated and 836 downregulated. GO and KEGG pathway analyses showed that a wide range of biological functions were perturbed during acute anti-NMDAR encephalitis. Differentially expressed genes were found to be involved in autoimmune, B cell signaling, neuroinflammation, or synaptic plasticity. qRT-PCR was conducted in 11 patients and 11healthy controls to further confirm the levels of six lncRNAs and four mRNAs, and the results were found to be consistent with those by RNA sequencing. The co-expression networks of lncRNA-mRNA were performed in some meaningful KEGG analyses, including chemokine signaling pathway, Long-term potentiation, B cell receptor signaling pathway and MAPK signaling pathway. Conclusions: Taken together, these findings suggest the involvement of a number of molecular pathways in anti-NMDAR encephalitis, some of which could serve as potential biomarkers to assist in diagnosis, treatment and prognosis.
Project description:Purpose of reviewArbovirus (arthropod-borne virus) infections are increasingly important causes of neurologic disease in the United States through both endemic transmission and travel-associated infections. This article reviews the major arbovirus infections that can cause neurologic disease likely to be encountered in the United States.Recent findingsWest Nile virus continues to be an important cause of epidemic encephalitis, while emerging arbovirus infections such as dengue and chikungunya have rapidly expanded their geographic distribution. As emerging arboviruses expand in new geographic regions, neurologic abnormalities are reported in new patient populations.SummaryEmerging arbovirus infections are increasingly important causes of neurologic disease throughout the world and in the United States. While no US Food and Drug Administration (FDA)-approved therapy is yet available for these infections, prompt recognition and diagnosis from the consulting neurologist will ensure appropriate supportive care for the patient.
Project description:Background: The diagnosis and monitoring of Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis typically rely on clinical manifestations and the detecting of anti-NMDAR antibodies. However, several studies have found that anti-NMDAR IgG in serum is not entirely specific and can be detected in about 3% of healthy individuals. Objective: To identify novel biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: We enrolled 9 patients with anti-NMDAR encephalitis and categorized them into an acute-phase group and a stable-phase group based on the duration of illness and disease severity. The clinical severity of the patients was assessed using the modified Rankin Scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). Then, we isolated exosomal miRNAs from plasma samples and analysed the differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using RT-qPCR. Furthermore, we conducted correlation analyses between miRNAs and clinical severity. Finally, we performed the functional pathways analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We have found that exosomal miR-432-5p, miR-4433b-5p and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at different stages of the disease. The expressions of miR-432-5p and miR-4433b-5p were negatively correlated with both the mRS and the CASE. We further identified that the pathways involved in rhythmic processes and neuroinflammation, as well as glutamatergic signaling, play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicates that exosomal miR-432-5p, miR-4433b-5p and miR-599 were highly correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. We further identified the pathways play significant roles in anti-NMDAR encephalitis. By modulating the functions of these crucial pathways, we can potentially uncover novel therapeutic targets and improve patient outcomes.
Project description:Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria. Thirty-five genes were identified that best discriminate patients with influenza A virus infection from patients with either E coli or S pneumoniae infection. These genes classified with 95% accuracy (35 of 37 samples) an independent set of patients with either influenza A, E coli, or S pneumoniae infection. A different signature discriminated patients with E coli versus S aureus infections with 85% accuracy (34 of 40). Furthermore, distinctive gene expression patterns were observed in patients presenting with respiratory infections of different etiologies. Thus, microarray analyses of patient peripheral blood leukocytes might assist in the differential diagnosis of infectious diseases. Keywords: expression analysis