Transcriptomic signatures of classical monocytes reveal pro-inflammatory modules and heterogeneity in polyarticular juvenile idiopathic arthritis.

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.

Incidence and prevalence of alopecia areata in the Australian primary care setting: A retrospective analysis of electronic health record data.

BACKGROUND: Alopecia areata (AA) is a common immune-mediated non-scarring hair loss, with a worldwide incidence between 0.57% and 3.8%. The incidence and prevalence of AA in the Australian general population have not been previously reported. OBJECTIVE: To describe the incidence and prevalence of AA in Australia using primary care data. A secondary objective was to identify common demographic characteristics, comorbidities and treatment patterns among Australians living with AA. METHODS: We analysed electronic health record data captured from a national clinical practice management software over a 10-year index period between 2011 and 2020 calendar years, inclusive. The incidence of new-onset AA and the prevalence of active records with AA were estimated. Differences in incidence by sociodemographic groups, and patterns of treatment were also evaluated. RESULTS: There were 976 incident AA records. The incidence of new-onset AA in the total study cohort was 0.278 per 1000 person-years (95% CI 0.26-0.295). By age, the incidence was highest in the 19- to 34-year-old age bracket (0.503 per 1000 person-years: 95% CI 0.453-0.554). AA incidence was lower among females than males (IRR 0.763, p < 0.001, 95% CI 0.673-0.865). Among active records, 520 were prevalent AA records. AA point prevalence at 31/12/2020 was 0.13% (1.26 per 1000 persons; 95% CI 1.15-1.37). CONCLUSION: This is the first study to describe the epidemiology (incidence and point prevalence) and management of AA in the Australian primary health-care population through large-scale database analysis. Incidence and prevalence findings were consistent with earlier estimates from other regions.