Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The pathogenesis of SLE involves disturbances to the homeostatic balance between the immune effector and regulatory system. The conventional mono-dimensional mechanistic interrogation of one cell type or molecule at a time is inadequate for a multifactorial disease such as lupus where multiple derangements contribute to disease causation and progression. The ability to scrutinise multiple components and both arms of the immune balance simultaneously is a critical unmet need. We hypothesise that abnormalities of different components within the immune-regulatory mechanism contributes to lupus pathogenesis. To address such unmet needs and hypotheses, we employed a multi-dimensional approach to study the immunome of jSLE patients. This approach may have immediate translational value of identifying immune cell subsets relevant for clinical prognostication and elucidation of mechanism to single out therapeutic targets.
Methods: Peripheral blood mononuclear cells from 14 jSLE patients out of a cohort of 58, stratified by clinical scoring (SLEDAI and SLE activity score) into active and inactive disease, were interrogated with multi-dimensional mass cytometry (Cytometry by time-of-flight). Active disease is defined as persistent activity/refractory to treatment, flare or new diagnosis of lupus. Analysis was performed using a machine learning custom software through an unbiased, unsupervised approach based on dimensional reductions followed by automated cell classification, clustering and visualisation.
Results: Significant immunome differences stratified by disease activity were found. In active disease, enrichment of a CD45RA+ (naive) CD38+ CD4+ cell population was observed; indicative of a potential novel T cell involvement in lupus flare. Concurrently, a counterintuitive increase in the natural regulatory T cell (CD25+ CD152+ Foxp3+) population in active disease was found. This observation likely underscores an ineffective attempt of the T regulatory system to overcompensate the inflammatory response. This is in contrast to a greater degree of B regulatory cells (CD19+ IL10+) expansion with inactive disease after CpG oligodeoxynucleotides challenge (inactive: 3.56%, interquartile range (IQR): 3.18% to 6.84%; active: 2.12%, IQR: 2.02% to 2.20%) (not significant, Mann Whitney u test). Significance of these changes will be determined with increasing sample size.
To cite this abstract in AMA style:Yeo JG, Arkachaisri T, Tan JHT, Leong JY, Das L, Bathi LDT, Chen P, Albani S. A Dichotomy of Regulatory Immunome Is Related to Disease Activity in Juvenile Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-dichotomy-of-regulatory-immunome-is-related-to-disease-activity-in-juvenile-systemic-lupus-erythematosus/. Accessed November 23, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-dichotomy-of-regulatory-immunome-is-related-to-disease-activity-in-juvenile-systemic-lupus-erythematosus/