title: Differential expression of T-cell genes in blood and bone marrow between ITP patients and controls.
abstract: Primary immune thrombocytopenia (ITP) is an autoimmune disease characterised by premature platelet destruction in spleen, liver and bone marrow and a diminished production of platelets. T-cells are important in all forms of autoimmunity including ITP; however, very little is known about T-cells in organs where platelets are destroyed. Our aim was to investigate differences in gene expression in peripheral blood-derived T-cells and bone marrow-derived T-cells between ITP patients and controls. T-cells and subsequent RNA were isolated from blood and bone marrow from chronic ITP patients and healthy controls followed by DNA microarray analysis. There were 1554 differentially expressed genes in peripheral blood-derived T-cells and 976 in bone marrow-derived T-cells between ITP patients and controls and three genes were verified with real-time PCR. Using Gene Ontology functional enrichment analysis we found that genes involved in growth, development, migration, chemotaxis, adhesion and apoptosis were enriched in bone marrow-derived T-cells in ITP. Immune-related genes involved in T-helper cell differentiation, T-cell chemotaxis, migration, immunoglobulin-mediated immune response and classical and alternative pathway complement activation were also enriched in bone marrow-derived T-cells in ITP. Only 213 T-cell genes were differentially expressed in both blood and bone marrow between ITP patients and controls. In conclusion, our findings show that genes involved in major pathophysiologic pathways in ITP such as T-helper cell differentiation, autoantibody response and complement activation are altered in bone marrow-derived T-cells in ITP patients compared with controls. This further supports the concept that bone marrow is an important compartment in ITP.
authors.affiliation: Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Vita Stråket 12, SE-413 45 Gothenburg, Sweden. margareta.jernas@medic.gu.se
authors.forename: Margareta
authors.initials: M
authors.lastname: Jernås
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.forename: Hans
authors.initials: H
authors.lastname: Wadenvik
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics*; D001853:Bone Marrow / Q000276:immunology*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D003167:Complement Activation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D012313:RNA / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D012313:RNA