Is clonal haematopoiesis the missing link between lupus and cardiovascular disease?

Area of Science:

• Immunology
• Cardiovascular Medicine
• Hematology

Background:

• Systemic lupus erythematosus (SLE) is a significant independent risk factor for premature cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD).
• The pro-inflammatory immune phenotype associated with clonal hematopoiesis of indeterminate potential (CHIP), driven by myeloid cells, is also strongly linked to ASCVD.
• CHIP driver mutations are found enriched in hematopoietic stem and progenitor cells (HSPCs) within chronic inflammatory conditions like SLE.

Purpose of the Study:

• To explore the emerging role of CHIP in the relationship between SLE and ASCVD.
• To propose CHIP as a pathogenic nexus connecting SLE and ASCVD through a triangular inflammatory network.
• To aid in the early identification of high-risk individuals and guide therapeutic strategies targeting CHIP.

Main Methods:

• This is a review article, synthesizing existing research on SLE, CHIP, and ASCVD.
• The review examines the interplay of cellular and molecular inflammatory pathways in SLE and CHIP.
• It analyzes shared mechanisms of immune dysregulation contributing to accelerated CVD.

Main Results:

• SLE and CHIP may synergistically accelerate CVD through combined inflammatory pathways.
• CHIP could represent a convergence point for immune dysregulation in SLE patients, exacerbating cardiovascular risk.
• Understanding this nexus can refine risk stratification and therapeutic interventions.

Conclusions:

• CHIP emerges as a potential pathogenic nexus in the inflammatory network linking SLE and ASCVD.
• Identifying CHIP in SLE patients may allow for targeted therapies to mitigate ASCVD risk.
• Further research into this triangular inflammatory network is crucial for cardiovascular risk management in SLE.