Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Arends, Christopher Maximilian; Weiß, Marlene; Christen, Friederike; Eulenberg-Gustavus, Claudia; Rousselle, Anthony; Kettritz, Ralph; Eckardt, Kai‐Uwe; Chan, Willy; Hoyer, Kaja; Frick, Mareike; Bullinger, Lars; Bieringer, Markus; Schreiber, Adrian; Damm, Frédérik

doi:10.3324/haematol.2019.223305

Cited by 68 publications

(45 citation statements)

References 4 publications

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“…A small, retrospective study of 112 patients with anti-neutrophilic cytoplasmic autoantibody-associated vasculitis (AAV) reported a higher prevalence of CHIP, albeit compared with previously reported cohorts [62]. AAV patients with CHIP also presented with different organ manifestations compared with non-CHIP patients [62]. Epigenetic dysregulation driven by DNMT3A and TET2 mutations may contribute to these disease-modifying effects because there is an epigenetic basis to inappropriate expression of neutrophil granule proteins in human vasculitis [63].…”

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

“…It will be interesting to determine whether CHIP has a disease-modifying role in other conditions associated with neutrophils as effector cells. For example, there is some evidence that CHIP may influence the disease course of vasculitis [62], which is a disease of small blood vessel inflammation and is also mediated by neutrophils. A small, retrospective study of 112 patients with anti-neutrophilic cytoplasmic autoantibody-associated vasculitis (AAV) reported a higher prevalence of CHIP, albeit compared with previously reported cohorts [62].…”

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

“…For example, there is some evidence that CHIP may influence the disease course of vasculitis [62], which is a disease of small blood vessel inflammation and is also mediated by neutrophils. A small, retrospective study of 112 patients with anti-neutrophilic cytoplasmic autoantibody-associated vasculitis (AAV) reported a higher prevalence of CHIP, albeit compared with previously reported cohorts [62]. AAV patients with CHIP also presented with different organ manifestations compared with non-CHIP patients [62].…”

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

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Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Cook

Luo

Rauh

2020

Experimental Hematology

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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.

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Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

Section: Ch As a Consequence Of Inflammationmentioning

confidence: 99%

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Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Cook

Luo

Rauh

2020

Experimental Hematology

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“… 9 , 10 A clear pathogenic contribution of CH to other inflammatory diseases has not yet been formally established but it is an active area of research. 13 - 15 …”

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confidence: 99%

Clonal Hematopoiesis in Hospitalized Elderly Patients With COVID‐19

et al. 2020

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“…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]. The youngest participant with CHIP was 18 years old; however, the median age of patients with CHIP was higher than that of CHIPnegative patients (70.5 years compared with 63.0 years).…”

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

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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.

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Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Cited by 68 publications

References 4 publications

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity

Clonal Hematopoiesis in Hospitalized Elderly Patients With COVID‐19

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

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