Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder that arises from genetic and environmental factors. Thus, patients with different ancestral backgrounds display differences in clinical presentation and severity that are likely a result of variation in cell physiology. Prior to SLE diagnosis, most SLE patients transition from anti-nuclear antibody negative (ANA-) to anti-nuclear antibody positive (ANA+), however, ANA positivity does not obligate autoimmune disease. Understanding differences in immune cell physiology between ANA+ healthy individuals and individuals that go on to clinical SLE remains a critical goal in the understanding of SLE etiology and is likely to vary by ethnicity.
Methods: Blood specimens and information on disease activity were collected from 56 European American (EA) and 38 African American (AA) individuals classified as either ANA- healthy controls, ANA+ healthy individuals or SLE patients. SLE patients were matched by age (±5 years), race, and gender to an ANA+ and ANA- healthy control. Single-cell analysis of cell surface markers was completed by mass cytometry on PBMCs and cellular heterogeneity was visualized using viSNE. Further, phospho-specific flow cytometry was used to measure basal levels of pERK, pPLCγ2 and p38 and expression following CD3/CD28 (TCR) and anti-IgG and IgM (BCR) stimulation.
Results: Compared to ANA- controls, EA ANA+ individuals had a higher frequency of myeloid cells (p=0.048), specifically myeloid derived suppressor-like cells (CD33+CD11b+HLA-DR–CD14±) were higher in ANA+ individuals (p=0.037) compared to SLE patients. Further, EA SLE patients had an increased frequency of CD14+CD33– activated monocytes compared to healthy controls (p<.05), which positively correlated with SLEDAI disease activity (p=0.040). EA effector T cells had elevated basal levels of p38 and pERK (p<0.005) in ANA+ individuals compared to ANA- controls. However, following TCR stimulation, the fold change of pERK and p38 in effector CD4+ T cells was significantly decreased in ANA+ individuals and remained the same in SLE patients compared to ANA- controls (p<0.05). Interestingly, AA SLE patients and ANA+ individuals had no myeloid cell differences, but did have variations in B cell and CD4+ T cell subsets. Decreased frequencies of transitional B cells (CD27–CD38+CD24+) were observed in AA SLE patients compared to both healthy controls (p=.007). In addition, CD4+CD27+ T cells were elevated in AA SLE patients compared to controls (p<0.05). AA SLE patients had higher basal expression of p38 and pERK in myeloid cell subsets. Following BCR stimulation, ANA+ AA individuals had increased fold change in myeloid cell pERK compared to ANA- controls (p=0.026), however, B cell pERK expression following BCR stimulation was decreased in SLE patients compared to ANA+ individuals (p=.0225).
Conclusion: Our results indicate that early differences in myeloid cell subsets of European Americans and lymphocyte subsets of African Americans may contribute to loss of tolerance and systemic inflammation in autoimmunity. Further, differences in cell signaling in SLE patients and ANA+ individuals may enhance these defects.
To cite this abstract in AMA style:Slight-Webb S, Lu R, Maecker HT, Utz PJ, Guthridge JM, James JA. Divergent Phenotypic Patterns Between Systemic Lupus Erythematosus and Healthy Anti-Nuclear Antibody Positive Individuals Reveal Distinct Differences in B Cell and Myeloid Populations Among Ethnicities [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/divergent-phenotypic-patterns-between-systemic-lupus-erythematosus-and-healthy-anti-nuclear-antibody-positive-individuals-reveal-distinct-differences-in-b-cell-and-myeloid-populations-among-ethnicitie/. Accessed November 11, 2019.
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