TY - JOUR
T1 - Cardiovascular risk in ANCA-associated vasculitis
T2 - Monocyte phenotyping reveals distinctive signatures between serological subsets
AU - Vegting, Yosta
AU - Hanford, Katie Ml
AU - Jongejan, Aldo
AU - Gajadin, Gayle Rs
AU - Versloot, Miranda
AU - van der Bom-Baylon, Nelly D
AU - Dekker, Tamara
AU - Penne, E Lars
AU - van der Heijden, Joost W
AU - Houben, Eline
AU - Bemelman, Frederike J
AU - Neele, Annette E
AU - Moerland, Perry D
AU - Vogt, Liffert
AU - Kroon, Jeffrey
AU - Hilhorst, Marc L
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/10
Y1 - 2024/10
N2 - BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.METHODS: A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.RESULTS: Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV.CONCLUSIONS: These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.
AB - BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.METHODS: A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.RESULTS: Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV.CONCLUSIONS: These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.
KW - ANCA-associated vasculitis
KW - Cardiovascular disease
KW - Leukocyte extravasation
KW - Macrophage
KW - Monocyte
UR - https://www.scopus.com/pages/publications/85201780817
U2 - 10.1016/j.atherosclerosis.2024.118559
DO - 10.1016/j.atherosclerosis.2024.118559
M3 - Article
C2 - 39186910
SN - 0021-9150
VL - 397
SP - 118559
JO - Atherosclerosis
JF - Atherosclerosis
M1 - 118559
ER -
