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

© 2021 by The American Society of Hematology..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:138

Enthalten in:

Blood - 138(2021), 18 vom: 04. Nov., Seite 1727-1732

Sprache:

Englisch

Beteiligte Personen:

Hecker, Judith S [VerfasserIn]
Hartmann, Luise [VerfasserIn]
Rivière, Jennifer [VerfasserIn]
Buck, Michèle C [VerfasserIn]
van der Garde, Mark [VerfasserIn]
Rothenberg-Thurley, Maja [VerfasserIn]
Fischer, Luise [VerfasserIn]
Winter, Susann [VerfasserIn]
Ksienzyk, Bianka [VerfasserIn]
Ziemann, Frank [VerfasserIn]
Solovey, Maria [VerfasserIn]
Rauner, Martina [VerfasserIn]
Tsourdi, Elena [VerfasserIn]
Sockel, Katja [VerfasserIn]
Schneider, Marie [VerfasserIn]
Kubasch, Anne S [VerfasserIn]
Nolde, Martin [VerfasserIn]
Hausmann, Dominikus [VerfasserIn]
Paulus, Alexander C [VerfasserIn]
Lützner, Jörg [VerfasserIn]
Roth, Andreas [VerfasserIn]
Bassermann, Florian [VerfasserIn]
Spiekermann, Karsten [VerfasserIn]
Marr, Carsten [VerfasserIn]
Hofbauer, Lorenz C [VerfasserIn]
Platzbecker, Uwe [VerfasserIn]
Metzeler, Klaus H [VerfasserIn]
Götze, Katharina S [VerfasserIn]

Links:

Volltext

Themen:

DNA Methyltransferase 3A
DNA-Binding Proteins
DNMT3A protein, human
Dioxygenases
EC 1.13.11.-
EC 2.1.1.37
Journal Article
Research Support, Non-U.S. Gov't
TET2 protein, human

Anmerkungen:

Date Completed 09.12.2021

Date Revised 14.12.2021

published: Print

Citation Status MEDLINE

doi:

10.1182/blood.2020010163

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM326865497