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Hecker, J.S.* ; Hartmann, L.* ; Riviere, J.* ; Buck, M.C.* ; van der Garde, M.* ; Rothenberg-Thurley, M.* ; Fischer, L.* ; Winter, S.* ; Ksienzyk, B.* ; Ziemann, F.* ; Solovey, M.* ; Rauner, M.* ; Tsourdi, E.* ; Sockel, K.* ; Schneider, M.* ; Kubasch, A.S.* ; Nolde, M.* ; Hausmann, D.* ; Paulus, A.C.* ; Lützner, J.* ; Roth, A.* ; Bassermann, F.* ; Spiekermann, K.* ; Marr, C. ; Hofbauer, L.C.* ; Platzbecker, U.* ; Metzeler, K.H.* ; Götze, K.S.*

CHIP & HIPs: Clonal hematopoiesis is common in hip arthroplasty patients and associates with autoimmune disease.

Blood 138, 1727-1732 (2021)
Postprint Research data DOI
Open Access Green
Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA). THA-derived hip bones serve as a major source of 'healthy' hematopoietic cells in experimental hematology. We prospectively investigated frequency and clinical associations of CH in 200 patients without known hematologic disease undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variants with allele frequencies [VAF] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF 1-2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%) and ASXL1 (3.5%). CHIP significantly associated with lower hemoglobin, higher mean corpuscular volume, prior/present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AID; multivariate adjusted odds ratio, 6.6; 95% confidence interval [1.7, 30]; p=0.0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for management of patients with OA and AID or mild anemia, and question use of hip bone-derived cells as 'healthy' experimental controls.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Risk
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 138, Issue: 18, Pages: 1727-1732 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place 2021 L St Nw, Suite 900, Washington, Dc 20036 Usa
Reviewing status Peer reviewed
Grants Deutsche Forschungsgemeinschaft
German Jose Carreras LeukaEuromiestiftung
Wilhelm Sander Stiftung
European Research Council (ERC) under the European Union's Horizon 2020 Marie Sklodowska-Curie Innovative Training Network
ERC under the European Union's Horizon 2020 Research and Innovation Programme
German Cancer Consortium joint funding program (DKTK CHOICE)