MICEPAP Trial
Ontology highlight
ABSTRACT: The purpose of this study is to (1) compare a technically improved assay with an existing assay used to measure serum anti-GM-CSF antibodies in stored serum samples previously obtained from patients diagnosed with either primary, secondary, congenital or idiopathic pulmonary alveolar proteinosis (PAP), other chronic diseases or disease-free, healthy individuals; (2) determine the prevalence and levels of anti-GM-CSF autoantibodies and (3) define the breadth of the autoimmune antibody responses in primary PAP patients from the United States, Japan, Australia, and Europe using previously collected serum samples; and (4) using a chart review approach, compare the clinical, radiologic and laboratory features of primary PAP patients to determine if differences exist among patients in these globally geographically distributed regions.
SECONDARY ACCESSION(S): PRJNA377202PRJNA377201
REPOSITORIES: dbGaP
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2021-03-25 | MSV000087099 | MassIVE
Project description:COVID-19 patients frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single cell RNA-seq and cytokine analyses of CSF and blood from COVID-19 patients with neurological symptoms, we find compartmentalized, CNS specific T cell activation and B cell responses. All COVID-19 cases had CSF anti-SARS-CoV-2 antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are found only during brain infection, and are not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from a COVID-19 patient, and find that these mAbs target both anti-viral and anti-neural antigens including one mAb that reacted to both spike protein and neural tissue. Overall, CSF IgG from 5/7 patients contains anti-neural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of COVID-19 patients and suggests a role for autoimmunity in neurologic sequelae of COVID-19.
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Project description:Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
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2022-09-02 | MTBLS863 | MetaboLights
Project description:Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. Unlike phospholipase A2 receptor or thrombospondin type 1 domain containing 7A-associated membranous nephropathy, where known antibodies can be detected within sera by indirect immunofluorescence and/or enzyme-linked immunosorbent assay, it is not possible to monitor disease activity in membranous lupus nephritis where the target autoantigens are mostly unknown. Determination of the target autoantigen has diagnostic significance, informs prognosis, and allows for non-invasive monitoring of disease activity in serum. We utilized mass spectrometry for antigen discovery of laser capture microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue IgG immunoprecipitation studies from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1-associated membranous neuropathy was 5.7% of cases of membranous lupus nephritis. NCAM1 co-localizes with IgG within glomerular immune deposits. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring of the disease. We propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.
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Project description:Animals: Specific pathogen-free male Wistar-Kyoto rats weighing 300 to 350 g (Charles River Japan, Kanagawa, Japan) were used. Experiments were performed according to institutional guidelines. Anti-GBM GN: GBM antigen for the rats was prepared as described previously(1,2). Five albino rabbits were immunized subcutaneously with GBM antigen emulsified with Freund's complete adjuvant (Difco Laboratories, Detroit, MI, USA). A booster was given three times every two weeks using the same antigen. Four days after the final booster, the rabbits were bled from the carotid artery under anesthesia. Anti-GBM sera were heat-decomplemented for 30 min at 56 degrees Celsius and absorbed with freshly harvested rat erythrocytes. Rats were divided into several groups, each of which consisted of 4 to 8 rats. The rats assigned to the GN groups were injected in the dorsal tail vein with 3 ml/kg of anti-GBM serum diluted ten-fold with saline under ether anesthesia. The day of the anti-GBM serum injection was defined as day 0. The rats assigned to the control groups were injected intravenously with the same volume of non-immune rabbit control serum, for comparison with the anti-GBM GN rats. The general condition and body weight of the rats was observed over the course of the experiments. Drug Treatment: Prednisolone (Shionogi Pharmaceutical, Osaka, Japan) was administered orally at 1 mg/kg body weight twice a day from day 14 of anti-GBM serum injection until sacrifice. cDNA microarray analysis: NCH_RAT_SLK array contains about 3000 distinct cDNAs from a normalized rat kidney cDNA library. cDNAs were spotted on the slide glass with MAS coated surface (Matsunami, Osaka, Japan) and irradiate UV for cross-linking. Non-spotted surface was blocked with succinic anhydride. Total RNA was prepared from each renal cortex by a guanidinium isothiocyanate method using ISOGEN reagent (Nippon Gene, Tokyo, Japan), and mRNA was prepared by using Oligotex-dT30 (Takara, Shiga, Japan), according to the manufacturer's instructions. We hybridized labeled target DNAs on the cDNA microarrays with overnight incubation at 65 degrees Celsius. Hybridization images were scanned using a GenePix 4000A scanner (Axon Instruments, Union City, CA), and the signal intensities were quantified with GenePix Pro 3.0 software (Axon Instruments). Data analysis was performed(3,4). In brief, quantified signal intensities were converted by taking logarithms in base two. Using transformed data derived from each pair of competitive hybridization images, we drew scatter diagrams to compare sample signal intensities with those derived from controls, and executed regression analysis. The given residuals explain logarithmic gene expression ratios. Therefore, we selected genes whose average residuals were more than 1 or less than â1, i.e. they represented a two-fold difference in expression level. References 1. Yamada, M., Sasaki, R., Sato, N., Suzuki, M., Tamura, M., Matsushita, T., Kurumatani, H.Amelioration by beraprost sodium, a prostacyclin analogue, of established renal dysfunction in rat glomerulonephritis model. Eur. J. Pharmacol. 449, 167-176 (2002). 2. Krakower, C.A., Nicholes, B.K., Greenspon, S.A. Proteinuria and the fragility of normal and diseased glomerular basement membrane. Proc. Soc. Exp. Biol. Med. 159, 324-334 (1978). 3. Katsuma, S., Shiojima, S., Hirasawa, A., Suzuki, Y., Takagaki, K., Murai, M., Kaminishi, Y., Hada, Y., Koba, M., Muso, E., Miyawaki, S., Ohgi, T., Yano, J., Tsujimoto, G. Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF-EDG5 cascade. Pharmacogenomics J. 1, 211-217 (2001). 4. Dong, G., Loukinova, E., Chen, Z., Gangi, L., Chanturita, T.I., Liu, E.T., Van Waes, C. Molecular profiling of transformed and metastatic murine squamous carcinoma cells by differential display and cDNA microarray reveals altered expression of multiple genes related to growth, apoptosis, angiogenesis, and the NF-kappaB signal pathway. Cancer Res. 61, 4797-4808 (2001).
2010-06-05 | E-GEOD-1262 | biostudies-arrayexpress
Project description:CD34+ hematopoietic stem and progenitor cells were isolated immunomagnetically from patients with multiple myeloma during chemotherapy and G-CSF-induced mobilization. Patients received either unconjugated G-CSF (n=9) or polyethylenglykol (PEG)-conjugated G-CSF (n=7). From each patient only one sample was analyzed. Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays according to manufacturer's instructions. Following quality control and normalization 9 samples of G-CSF-mobilized CD34+ cells were compared with 7 samples of PEG-G-CSF-mobilized cells were compared by significance analysis of microarrays (SAM). The aim was to figure out transcriptional differences resulting from various pharmacokinetics of the same drug (G-CSF: fluctuating serum levels; PEG-G-CSF: continously high serum levels). Peripheral blood stem and progenitor cells (PBSC) are widely used for autologous and allogeneic hematopoietic stem cell transplantation. PBSC can be mobilized into the peripheral blood using cytokines, cytotoxic chemotherapy or a combination of both. Granulocyte colony stimulating factor (G-CSF) has become the most commonly administered cytokine for PBSC mobilization because of its high potency and lack of serious toxicity. Recently, a modified form of recombinant human G-CSF has been introduced. This new compound is pegylated G-CSF (Peg-G-CSF) which possesses a substantially longer half-life than the unconjugated drug because of its reduced renal excretion and therefore provides the basis for continuous G-CSF serum-levels after a single injection. The use of Peg-G-CSF in patients who had received a cytotoxic chemotherapy was accompanied by mobilization kinetics different from those observed in patients who had received unconjugated G-CSF. In particular, more rapid leukocyte recovery and occurrence of CD34-positive cells in the peripheral blood was seen. These findings are presumably related to the more even and continuously high serum level of G-CSF maintained by Peg-G-CSF. Using microarray technology and functional assays, we examined whether pegylation of G-CSF and its different pharmacokinetics results in addition to an earlier leucocyte recovery in transcriptional and functional changes in CD34+ cells obtained from patients who had received either G-CSF or Peg-G-CSF following a standard cytotoxic chemotherapy for PBSC mobilisation. CD34+ hematopoietic stem and progenitor cells were isolated immunomagnetically from patients with multiple myeloma during chemotherapy and G-CSF-induced mobilization. Patients received either unconjugated G-CSF (n=9) or polyethylenglykol (PEG)-conjugated G-CSF (n=7). Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays. Following quality control and normalization differentially expressed genes were identified by significance analysis of microarrays (SAM). Comparing both groups 339 genes were significantly differentially expressed (q value <5%; fold change > 1.2). Peg-G-CSF-mobilized CD34+ cells showed an expression pattern of more early progenitor cells as early stem cell markers such as HOX genes were higher expressed and differentiation-associated genes were lower expressed in comparison with G-CSF-mobilized cells. Moreover, Peg-G-CSF-mobilized CD34+ cells had a greater expression level of cell-cycle-promoting genes suggesting a greater cycle activity of these cells. In conclusion, despite the similar active drug component different pharmacokinetics of Peg-G-CSF and G-CSF result in distinct molecular phenotypes reflecting different functional characteristics.
2007-10-26 | E-GEOD-4688 | biostudies-arrayexpress