gms | German Medical Science

45. Kongress der Deutschen Gesellschaft für Rheumatologie, 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

06.09. - 09.09.2017, Stuttgart

Different transcriptome profiles of CD4+CD8+ double-positive T-cells between granulomatosis with polyangiitis and healthy controls

Meeting Abstract

  • Anja Kerstein - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
  • Silke Schüler - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
  • Otavio Cabral-Marques - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
  • Juliane Fazio - Institut für Immunologie, Kiel
  • Robert Häsler - Institut für Molekularbiologie, Christian-Albrechts-Universität zu Kiel, Kiel
  • Silke Pitann - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
  • Antje Müller - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
  • Dieter Kabelitz - Institut für Immunologie, Kiel
  • Gabriela Riemekasten - Universität zu Lübeck, Klinik für Rheumatologie und Klinische Immunologie, Lübeck
  • Peter Lamprecht - Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Stuttgart, 06.-09.09.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocER.01

doi: 10.3205/17dgrh090, urn:nbn:de:0183-17dgrh0904

Published: September 4, 2017

© 2017 Kerstein et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background: We found increased frequencies of circulating CD4+CD8+ double-positive (DP) T-cells displaying markers of memory cell phenotype and function as well as innate features, activation and migratory potential in granulomatosis with polyangiitis (GPA). In contrast, only few circulating DP T-cells were found in healthy controls (HC). To investigate potential triggers and differences of DP T-cells, we compared the transcriptomic profile of CD4+ single-positive (SP), CD8+ SP and CD4+CD8+ DP T-cells in GPA and HC.

Methods: FACS-sorted SP and DP T-cells of GPA patients and HC (n=3 each) were subjected to transcriptional profiling using an Affymetrix Human Genome 2.0 microarray. Genes with a fold change < 2 or > 2 without overlap between GPA and HC were considered differently expressed genes (DEG). In order to categorize and integrate DEG to molecular interaction and reaction networks, GO functional enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery, the Kyoto Encyclopaedia of Genes and Genomes PATHWAY database and the Search Tool for the Retrieval of Interacting Genes/Proteins.

Results: By comparing the transcriptome profile of sorted T-cell populations from GPA to HC 418 DEG in CD4 SP, 359 DEG in CD8 SP, and 352 DEG in CD4CD8 DP T-cells were detected. Upregulated genes were grouped among several innate and inflammatory signaling pathways including toll-like receptor signaling, complement system and NOD-like receptor signaling both in SP and DP T-cells. DP T-cells displayed an even stronger up-regulation of several genes compared to SP T-cells in GPA.

Conclusion: Comparing transcriptome profiles of DP and SP T-cells in GPA to T-cells and HC disclosed potentially environmental factor-driven activation of innate immune pathways of DP T-cells in GPA. These findings suggest a link between autoimmune disease and infection-triggered pathology in GPA.