Clonal hematopoiesis in patients with rheumatoid arthritis

Savola, Paula; Lundgren, Sofie; Keränen, Mikko; Almusa, Henrikki; Ellonen, Pekka; Leirisalo‐Repo, Marjatta; Kelkka, Tiina; Mustjoki, Satu

doi:10.1038/s41408-018-0107-2

Cited by 74 publications

(51 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It seems reasonable to expect chronic inflammatory conditions to be enriched for CHIP. Although CHIP was not enriched in patients with rheumatoid arthritis [45], their ongoing treatments may have confounded its detection (i.e., suppressed potential clones).…”

Section: Potential Interventions To Mitigate Chip Risk and Its Comorbmentioning

confidence: 97%

“…Several chronic inflammatory conditions (e.g., 439patient cohort of treated aplastic anemia [44], a 187patient cohort of ulcerative colitis [39]), but not all (e. g., 59-patient cohort of treated rheumatoid arthritis [45]) have been reported to be enriched for CHIP. Often the reported rate of CHIP in such studies is compared with previously published rates, rather than the rate of a control group.…”

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Cook

Luo

Rauh

2020

Experimental Hematology

View full text Add to dashboard Cite

Clonal hematopoiesis (CH) of indeterminate potential (CHIP), defined as the presence of a somatic mutation in the peripheral blood at a variant allele frequency (VAF) ≥2%, affects at least 10% of individuals older than 65, but low-VAF clones can be detected in 95% of individuals older than 50. CHIP associates with a wide range of comorbidities from atherosclerosis to pulmonary disease. A growing body of evidence, primarily from studies involving Tet2-knockout and stem cell transplant models of CH, suggest that dysregulated inflammation contributes to clonal expansion and associated comorbidities. Mutant leukocytes from animal models contribute to an inflammatory milieu that may confer a selective advantage to the clone, thus perpetuating a cycle of inflammation and expansion. Although it is unclear whether inflammation or expansion sets this cycle in motion, some evidence suggests that inflammation from infections or pre-existing comorbidities initiates this cycle. The pro-inflammatory phenotypes of macrophages from mutant clones and their contributions to disease are well characterized in murine models, but have not yet been confirmed in humans. Furthermore, the roles of other cell types that can carry mutations of CHIP are not fully understood. We propose a rationale for further investigation of neutrophils, other granulocytes and T, B, and NK cells as they may play a role in CHIP-associated comorbidities. As the understanding of CH has advanced, potential interventions, especially those targeting aberrant inflammation, have been proposed. We are hopeful that as studies continue to unravel the complex links between CHIP, inflammation, and leukocyte dysfunction, CHIP-related comorbidities may be more effectively managed.

show abstract

Section: Potential Interventions To Mitigate Chip Risk and Its Comorbmentioning

confidence: 97%

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Cook

Luo

Rauh

2020

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…However, direct evidence demonstrating this is lacking. A recent study suggested patients with rheumatoid arthritis, a chronic inflammatory autoimmune disease, had no increased incidence of CHIP [14]. But as this patient cohort was relatively small, we sequenced 187 patients with ulcerative colitis (UC), an inflammatory bowel disease characterized by infiltration of T-cells in the colon and overproduction of pro-inflammatory cytokines such as TNFα and IFNγ, to evaluate the role of inflammation in CHIP.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory cytokines promote clonal hematopoiesis with specific mutations in ulcerative colitis patients

Zhang

Nix

Gregory

et al. 2019

Experimental Hematology

View full text Add to dashboard Cite

“…One study of 59 patients with RA (mean age: 54.7 years) identified CHIP clones in 17% of participants, with a prevalence of 25% in patients older than 70. They note that this is not significantly different from the incidence of CHIP in the general population and found mutations in DNMT3A, TET2, and ASXL1 to be the most common [115]. A slightly larger study of 112 patients with antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune vasculitis aged 18 to 84 identified CHIP in 30.4% of subjects-a prevalence much higher than that of an age-matched cohort [116].…”

Section: Inflammatory Stress and Chipmentioning

confidence: 94%

Clones assemble! The clonal complexity of blood during ontogeny and disease

Ganuza

Hall

Obeng

et al. 2020

Experimental Hematology

View full text Add to dashboard Cite

Hematopoietic stem and progenitor cells (HSPCs) govern the daily expansion and turnover of billions of specialized blood cells. Given their clinical utility, much effort has been made toward understanding the dynamics of hematopoietic production from this pool of stem cells. An understanding of hematopoietic stem cell clonal dynamics during blood ontogeny could yield important insights into hematopoietic regulation, especially during aging and repeated exposure to hematopoietic stress-insults that may predispose individuals to the development of hematopoietic disease. Here, we review the current state of research regarding the clonal complexity of the hematopoietic system during embryogenesis, adulthood, and hematologic disease.

show abstract

Clonal hematopoiesis in patients with rheumatoid arthritis

Cited by 74 publications

References 15 publications

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Inflammatory cytokines promote clonal hematopoiesis with specific mutations in ulcerative colitis patients

Clones assemble! The clonal complexity of blood during ontogeny and disease

Contact Info

Product

Resources

About