Background/Purpose Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder which arises from both genetic and environmental factors that likely affect phenotypic and functional characteristics of multiple cell lineages. Further, almost all SLE individuals are antinuclear antibody positive (ANA+) although ANA positivity does not obligate autoimmune disease. The differences in cellular physiology between ANA+ healthy individuals and individuals that go on to develop SLE remains a critical goal in the understanding of SLE development. A comprehensive view of immune cell phenotypes in disease is often challenging to ascertain due to limits of assay parameters and proper visualization tools to display cellular hierarchy for high-dimensional data sets. Using mass cytometry, we visualize the expression of 33 cell surface markers through hierarchical clustering using spanning-tree progression analysis of density-normalized events (SPADE) to provide a comprehensive view of the immune system between ANA- and ANA+ healthy controls and ANA+ patients with SLE.

Methods Blood specimens and information on disease activity were collected from eight African American SLE patients. Patients were matched by age (±5 years), race, and gender to healthy individuals positive for ANA without classifiable lupus (ANA+, n=8) and ANA negative healthy controls (ANA-, n=8). Single-cell analysis of cell surface markers was completed by mass cytometry and cellular heterogeneity was analyzed using SPADE. Significant differences in cell population frequencies were determined using ANOVA and Wilcoxon rank test. Plasma samples isolated from patients at time of draw were analyzed for 51 cytokines using a multiplex immunoassay.

Results Compared to both ANA+ and ANA- healthy controls, SLE patients had lower frequencies of cytotoxic CD8+ T cells, regulatory CD4+ T cells and early progenitor cell populations (P<0.05). Significant differences in progenitor cells nodes were found in CD4 and CD8 negative CD3+ T cells and surface marker null progenitor cells. Concentrations of serum sCD40 ligand were significantly lower in patients with SLE compared with ANA+ and ANA- healthy controls (p<0.05). Interestingly, sCD40L production positively correlated with a decrease in regulatory CD4+ T cell populations (p<0.01). Further, IL-7 levels were lower in both ANA+ controls and SLE patients compared with ANA- healthy individuals (p<0.05).

Conclusion Our results indicate that early differences in progenitor cell populations may contribute to decreased levels of regulatory CD8+ and CD4+ T cells important for controlling systemic inflammation. Further, the decreased production of IL-7, which is important for the differentiation of hematopoietic stem cells into lymphoid progenitors, in SLE patients and ANA+ patients may contribute to early immune defects in progenitor lymphoid populations leading to loss of tolerance in autoimmunity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-systemic-lupus-erythematosus-and-healthy-anti-nuclear-antibody-positive-african-americans-reveals-distinct-differences-in-t-cell-and-progenitor-populations/