Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Systemic Lupus Erythematosus (SLE) is a multi-factorial disease and the conventional oligo-dimensional investigative approach involving one or a few cell subsets at a time is inadequate for its study. We hypothesize that multiple immunological abnormalities contribute to lupus pathogenesis and hence, a comprehensive holistic interrogative strategy is required. To address these issues, we employ a multi-dimensional, deep immunophenotyping approach using mass cytometry to unravel the pathogenic mechanism underpinning childhood onset SLE (cSLE).
Peripheral blood mononuclear cells from 14 cSLE patients and 14 healthy paediatric controls, were stained with 37 immune phenotypic markers for mass cytometry. Subsequent analysis of the data was done with dimensional reductions followed by automated cell classification, clustering and visualization using an in-house customized machine learning software (MARVis: Multi-dimensional Automated Reduction and Visualization). Unique nodes representing immune subsets enriched in cSLE patients were statistically evaluated with reference to the healthy cohort and the association with lupus disease activity determined (Mann Whitney U Test, p < 0.05).
A statistically significant enrichment of a memory IL10 positive B cell subset (CD19+CD27+) with CD11c+CD25+HLA-DR+CD40hiCD86hi was found in the SLE cohort. This cell population was significantly associated with an inactive lupus disease state, suggestive of an immunoregulatory function. In the healthy cohort, a reciprocal increase in the transitional/naive B cell population negative for CD11c, CD25, CD40 and CD86 was found.
Secondly, a significant enrichment of the memory regulatory T cell population (CD4+CD45RO+CD25+Foxp3+) was present in the diseased cohort, especially during disease inactivity, with some of these cells being positive for CXCR5, a homing chemokine receptor to the lymph node germinal centre. Expression of CXCR5 is mechanistically relevant and signifies a potential regulatory role of these cells as the lymph node is an important lupus related microenvironment.
A holistic multi-dimensional approach was able to distill the immunoregulatory components of the cSLE immunome. The identification of a novel regulatory B cell subset, typified by the presence of IL10, with phenotypic markers for antigen presentation (HLA-DR, CD86) and T-B cell interaction (CD25, CD40) suggests its potential regulatory role during direct cell-to-cell interaction. In addition, the concomitant increase in the memory regulatory T cell subset suggests at least a dual regulatory mechanism responsible for quiescent disease. Further mechanistic study of these subsets is necessary and have the dual translational potential of being used as a predictor of clinical fate and identification of new therapeutic targets.
To cite this abstract in AMA style:Yeo JG, Arkachaisri T, Das L, Tan JHT, Leong JY, Tan YJA, Lai L, Bathi LDT, Chen P, Lee SCE, Book YX, Albani S. A Novel Regulatory Antigen Presenting B Cell and Memory Regulatory T Cell Subsets Are Enriched during the Quiescent Phase of Childhood Onset Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/a-novel-regulatory-antigen-presenting-b-cell-and-memory-regulatory-t-cell-subsets-are-enriched-during-the-quiescent-phase-of-childhood-onset-systemic-lupus-erythematosus/. Accessed May 20, 2018.
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