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CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease

造血 干细胞 造血干细胞移植 骨髓 髓样
作者
Judith S. Hecker,Luise Hartmann,Jennifer Rivière,Michèle C. Buck,Mark van der Garde,Maja Rothenberg-Thurley,Luise Fischer,Susann Winter,Bianka Ksienzyk,Frank Ziemann,Maria Solovey,Martina Rauner,Elena Tsourdi,Katja Sockel,Marie Schneider,A.S. Kubasch,Martin Nolde,Dominikus Hausmann,Alexander C. Paulus,Jörg Lützner,A. Roth,Florian Bassermann,Karsten Spiekermann,Carsten Marr,Lorenz C. Hofbauer,Uwe Platzbecker,Klaus H. Metzeler,Katharina Götze
出处
期刊:Blood [American Society of Hematology]
卷期号:138 (18): 1727-1732 被引量:5
标识
DOI:10.1182/blood.2020010163
摘要

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 who were undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variant allele frequencies [VAFs] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF, 1% to 2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%), and ASXL1 (3.5%). CHIP is significantly associated with lower hemoglobin, higher mean corpuscular volume, previous or present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AIDs; multivariable adjusted odds ratio, 6.6; 95% confidence interval, 1.7-30; P = .0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for managing patients with OA and AIDs or mild anemia and question the use of hip bone-derived cells as healthy experimental controls.
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