Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene Expression Signature Shared in Autoimmune Diseases Not in Unaffected Family Members

ABSTRACT: Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile reflects family resemblance rather than the actual presence of an autoimmune disease. Here we wanted to identify that portion of this gene expression pattern that is independent of family resemblance and determine if it is a product of disease duration, disease onset, or other factors. By increasing the number of autoimmune samples in our analysis and employing supervised clustering algorithms, we identified 100 genes whose expression profiles are shared in individuals with various autoimmune diseases but are not shared by first-degree relatives of individuals with autoimmune disease or by controls. Individuals with early disease (1 yr after onset) and established disease (10 yr after onset) exhibit a near identical expression pattern suggesting that this unique profile reflects disease onset rather than disease duration. supervised gene expression profiling were performed to a cohort sample pool: control individuals(8), unaffected family members of autoimmune diseases patients (8), and individuals with autoimmune diseases (54). we try to identify a gene expression signatures that were exclusively associated with autoimmune diseases but not infulenced by genetic components

ORGANISM(S): Homo sapiens

SUBMITTER: Zheng Liu

PROVIDER: E-GEOD-3447 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of gene expression signatures in autoimmune disease without the influence of familial resemblance.

Liu Zheng Z Maas Kevin K Aune Thomas M TM

Human molecular genetics 20051221 3

Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile is a property of familial resemblance rather than autoimmune disease. Here, we wanted to identify the portion of this gene expression profile that is independent of familial resemblance and determi ...[more]

PMID: 16371420

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Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5M-NM-<g/kg/day) and 4 MS patients (2 female) mobilized by G-CSF (5M-NM-<g/kg/day) plus Cyclophosphamide (Cy, 4g/m2). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human 4x44K Design Array (Agilent-Technologies).

Dataset Information

Gene Expression Signature Shared in Autoimmune Diseases Not in Unaffected Family Members

Publications

Identification of gene expression signatures in autoimmune disease without the influence of familial resemblance.

Similar Datasets

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