Background/Purpose: The pathogenesis of systemic sclerosis is not well understood. The key differences between immune cell compartments in scleroderma with and without interstitial lung disease remains unclear. We aimed to evaluate whether distinct immune cell subsets in peripheral blood are enriched or reduced in scleroderma patients with interstitial lung disease as compared to scleroderma without interstitial lung disease and healthy controls.

Methods: Peripheral blood was collected from scleroderma patients with or without interstitial lung disease who met the 2013 ACR scleroderma classification criteria, and matched healthy donors. We used a 38-parameter mass cytometry by time-of-flight panel to characterize lymphocyte and myeloid subsets. Dimensionality reduction algorithm t-distributed stochastic neighbor embedding (t-SNE) followed by supervised gating was performed to distinguish immune cell subsets. The p values were calculated using Kruskal-Wallis H test and Mann-Whitney + FDR for multiple test correction, as appropriate, using Cytobank platform.

Results: We identified decreased frequencies in CD4+ T cells in peripheral blood of scleroderma patients with interstitial lung disease (n=24, 28.01 ± 6.534%) as compared to healthy donors (n=18, 38.99 ± 6.76%, p=0.00012). CD8+ T cells were reduced in frequencies in scleroderma patients without interstitial lung disease (n=16, 14.97 ± 7.496%) versus healthy donors (22.45 ± 5.937%, p=0.01774). Proportions of B cells were lower in scleroderma patients with interstitial lung disease (6.404 ± 4.294%) compared to without interstitial lung disease (10.64 ± 5.331%, p=0.04529) and healthy donors (10.47 ± 4.579%, p=0.02010). Scleroderma patients with interstitial lung disease (4.371 ± 2.125%) were determined to have higher proportions of dendritic cells compared to without interstitial lung disease (2.766 ± 1.291%, p= 0.02611) and healthy donors (1.897 ± 0.802%, p=0.00011). We also found increased frequencies of non-classical monocytes in scleroderma patients with interstitial lung disease (4.082 ± 2.194%) versus healthy donors (1.811 ± 0.7086%, p=0.00011) as well as higher proportions of classical monocytes in scleroderma with (18.75 ± 7.098, p=0.00011) or without interstitial lung disease (18.55 ± 7.281%, p=0.00091) compared to healthy donors (9.254 ± 3.368%).

Conclusion: Patients with scleroderma-interstitial lung disease have distinct immune cell profile compared to healthy control donors. B cell and dendritic cell compartments appear to distinctly correlate with the presence or absence of interstitial lung disease in systemic sclerosis. Further work to investigate these populations may elucidate putative disease biomarkers or therapeutic drugs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-immune-cell-subsets-in-systemic-sclerosis-related-interstitial-lung-disease/