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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)

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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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