EULAR Rheumatology Open Special Issue titled 'VSI: ATT2026': the role of clonal haematopoiesis in immunological and rheumatological diseases.

Somatic mutations progressively accumulate in all tissues with age. Although most of these acquired mutations have no consequences on the cell's phenotype, some may occur in genetic regions that provide a small growth, survival, or self-renewal advantage to the mutant cells. These 'driver' gene mutations will lead to the clonal expansion of mutant cells. When clonal expansions occur in the blood system, they are referred to as 'clonal haematopoiesis' or 'clonal haematopoiesis of indeterminate potential' to distinguish these cellular expansions from overt haematological disease. The incidence of detectable clonal haematopoiesis increases with age, with relatively large clones detected using standard next-generation sequencing occurring in >10% of the population by 70 years of age. However, with the advent of error-corrected DNA sequencing, more recent studies have shown that smaller clones can be detected in most individuals by middle age and that this condition is an inevitable consequence of ageing. Emerging evidence reveals that the expansion of these mutant clones drives a systemic inflammatory state, significantly impacting the pathogenesis, severity, and therapeutic response across a spectrum of cardiovascular and autoimmune diseases. Additional clinical and experimental studies are warranted to address outstanding questions regarding disease causality, clinically relevant clone sizes, and driver gene-specific effects in these conditions.