Background/Purpose: Systemic Juvenile Idiopathic Arthritis (sJIA) is a unique subtype of juvenile idiopathic arthritis with life threatening complications including macrophage activation syndrome and chronic lung disease. Chronic lung disease encompasses interstitial lung disease, pulmonary fibrosis, pulmonary arterial hypertension, and pulmonary alveolar proteinosis, and associated with poor prognosis. The immunopathogenesis of sJIA lung disease (sJIA-LD) is poorly understood but has been associated with unique lymphocyte activation signatures. Our objective was to define myeloid and lymphoid subsets from sJIA-LD patients using high-parameter flow cytometry, and to correlate differences with disease activity.

Methods: Peripheral blood mononuclear cells (PBMC) were obtained from the CARRA Registry sJIA-LD cohort, after informed consent and approval from the CARRA Biorepository. Controls were healthy control children enrolled at CCHMC after informed consent. Full spectrum flow cytometry using the Auora platform was utilized, and cell populations were identified using manual gating. Previously reported from our lab, a high parameter flow cytometry panel (28-parameters) was created to investigate myeloid and lymphoid cell subsets (Table 1). Graph Pad PRISM was used to visualize and analyze the data. Statistical analysis utilized unpaired two-tailed t-test or Mann-Whitney for data that was not normally distributed. Relationships between physician global assessment of lung disease (PGALD) and cell populations used simple linear regression.

Results: We examined samples from 35 sJIA-LD patients and 7 controls. There was no significant difference between the number of live singlet cells and percentage of CD45+ cells in patients compared to controls. Overall, sJIA-LD patients had a significant increase in circulating monocyte percentage compared to controls, but no difference in relative abundance of monocyte subpopulations. There was a significant positive correlation between monocyte percentage and PGALD score, where a higher monocyte percentage correlates with higher PGALD score (R2=0.2761, p< 0.0034). We also found a significant decrease in lymphocyte percentage, with lower percentages similarly correlating with a higher PGALD score (Fig. 1). The sJIA-LD patients had similar percentages of CD4+ cells compared to controls. Further subdivision of CD4+ T-cells revealed a significantly lower percentages of central memory T-cells, Th1 cells, and Th17.1 cells in patients compared to controls (Fig. 2). We did not find any significant differences between CD8+ cells and their subsets.

Conclusion: Our results demonstrate an increase in peripheral monocytes in SJIA-LD patients, the degree of expansion positively correlated with higher disease activity. We also find differences in circulating lymphocyte profile in sJIA-LD patient versus controls. The consequences of this decrease in Th1, Th17.1, and central memory T-cells is unknown. Our future work involves comparison with SJIA patients without lung disease, as well as unsupervised analysis and evaluation of activation markers – all in hopes to better understand disease pathogenesis and predictors of disease severity in sJIA-LD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-immune-phenotypes-in-systemic-juvenile-idiopathic-arthritis-associated-lung-disease-sjia-ld-using-high-parameter-flow-cytometry/