Artikel
Bone marrow and blood monocytes from rheumatoid arthritis patients show premature transcriptomes and reveal incremental inflammatory activation from bone marrow to blood and joint
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Autoren
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Biljana Smiljanovic
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Till Sörensen
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Marc Bonin
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Bruno Stuhlmüller
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Andreas Radbruch
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Gerd-Rüdiger Burmester
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Wlodzimierz Maslinski
- Institute of Rheumatology - Poland, Warsaw
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Andreas Grützkau
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Thomas Häupl
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
| Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Most biologics for rheumatoid arthritis (RA) target processes involved in monocyte activation. To determine when, where and how monocytes become involved in pathogenesis of RA, we analysed monocytes from bone marrow, blood and synovial fluid by gene-expression profiling and cytometry, and compared their activation patterns with osteoarthritis (OA).
Methods: CD14+ cells purified from bone marrow and blood of RA and OA patients undergoing hip replacement surgery were profiled with GeneChip microarrays. Function of differentially expressed genes was investigated by gene ontology, ingenuity pathway analysis and 70 different reference transcriptomes of healthy bone marrow progenitors and various stages of activated and differentiated monocytes. Cytometry was applied for profiling of monocyte subsets: CD14+CD16-, CD14+CD16+ and CD14dimCD16+ in bone marrow, blood and synovial fluid samples.
Results: In RA monocytes, increased expression of progenitor related transcripts was dominant both in bone marrow and blood, indicating elevated monocytopoiesis, premature release into circulation and probably faster migration from blood into tissue. In OA, bone marrow monocytes were characterized with transcripts related to maturation and blood monocytes with increased patterns of CD14+CD16+ subset when compared to RA, suggesting longer retention periods in OA in both compartments. In addition, patterns associated with TNF and LPS stimulation were more extensive in RA blood than bone marrow monocytes.
Cytometric patterns of monocyte subsets from RA and OA patients were comparable in bone marrow with no or marginal expression of CD16 but revealed significantly lower levels of CD14dimCD16+ differentiated subset in RA blood. In contrast, RA synovial fluid monocyte subsets revealed all high levels of CD16 expression and three different levels of CD14 (high, medium or low) with CD14high as the prominent population.
Conclusion: In RA, monocytopoiesis is increased with premature release into circulation. Cytometry confirmed transcriptome data and suggests that CD16 expression on monocytes relates to differentiation after release from bone marrow with highest levels in inflamed tissue. Reduced levels of CD16+ monocytes in RA blood samples indicate either preferential chemotaxis or relate to a shorter period of circulation relative to differentiation. These data demonstrate the important role of monocytes in RA and indicate their diagnostic value as biosensors.
