RESUMEN
OBJECTIVE: Disease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever attainment of a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score of ≥10, is an indicator for disease severity in SLE. METHODS: Using prospectively collected data, we assessed the association of HDAS with sociodemographic and disease characteristics and adverse clinical outcomes using logistic regression or generalised estimating equations. RESULTS: Of 286 patients with SLE, who were observed for a median (range) of 5.1 years (1-10.8 years), 43.7% experienced HDAS at least once during the observational period. Autoantibody positivity, particularly anti-dsDNA and anti-Sm positivity, were associated with increased likelihood of HDAS. Age ≥45 years at diagnosis was associated with reduced likelihood of HDAS (p=0.002). Patients with HDAS had higher Physician Global Assessment score (>1: OR 8.1, p<0.001) and were more likely to meet criteria for flare (mild/moderate flare: OR 4.4, p<0.001; severe flare: OR 17.2, p<0.001) at the time of experiencing HDAS. They were also more likely to have overall higher disease activity, as defined by time-adjusted mean SLEDAI-2K score in the highest quartile (OR 11.7, 95% CI 5.1 to 26.6; p>0.001), higher corticosteroid exposure (corticosteroid dose in highest quartile: OR 7.7, 95% CI 3.9 to 15.3; p<0.001) and damage accrual (OR 2.3, 95% CI 1.3 to 3.9; p=0.003) when compared with non-HDAS patients. CONCLUSIONS: HDAS is associated with more severe disease, as measured by higher disease activity across time, corticosteroid exposure and damage accrual. The occurrence of HDAS may be a useful prognostic marker in the management of SLE.
Asunto(s)
Corticoesteroides/uso terapéutico , Autoanticuerpos/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/fisiopatología , Anciano , Australia/epidemiología , Estudios de Casos y Controles , Costo de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Organ growth requires a careful balance between stem cell self-renewal and lineage commitment to ensure proper tissue expansion. The cellular and molecular mechanisms that mediate this balance are unresolved in most organs, including skeletal muscle. Here we identify a long-lived stem cell pool that mediates growth of the zebrafish myotome. This population exhibits extensive clonal drift, shifting from random deployment of stem cells during development to reliance on a small number of dominant clones to fuel the vast majority of muscle growth. This clonal drift requires Meox1, a homeobox protein that directly inhibits the cell-cycle checkpoint gene ccnb1. Meox1 initiates G2 cell-cycle arrest within muscle stem cells, and disrupting this G2 arrest causes premature lineage commitment and the resulting defects in muscle growth. These findings reveal that distinct regulatory mechanisms orchestrate stem cell dynamics during organ growth, beyond the G0/G1 cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.