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Abstract Number: 2975

Using Immune and Metabolic Phenotyping to Understand the Immunopathogenesis of Juvenile-Onset SLE and Stratify Patient Groups

George Robinson1, Marsilio Adriani1, Ines Pineda Torra2, Yiannis Ioannou3 and Elizabeth Jury4, 1Centre for Rheumatoloy Research, University College London, London, United Kingdom, 2Centre for Clinical Pharmacology, University College London, London, United Kingdom, 3Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom, 4Division of Medicine, Centre for Rheumatology Research, University College London, London, United Kingdom

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: juvenile SLE, metabolism and phenotypes

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Session Information

Date: Wednesday, November 8, 2017

Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis II

Session Type: ACR Concurrent Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose:

Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder characterized by immune cell dysregulation, chronic inflammation and increased cardiovascular risk. Disease onset dominates mid-puberty and the female to male ratio is 4.5:1, suggesting a hormonal importance in disease pathogenesis. JSLE patients have more aggressive disease, more major organ involvement and increased standardised mortality ratios compared to patients with adult-onset SLE yet research into JSLE is uncommon. Our previous findings show that defects in immune cell lipid metabolism contribute to disease pathogenesis in adult-onset SLE. However, in JSLE little is known about the immune profile or whether abnormal lipid metabolism also contributes to pathogenesis. Here we performed in depth immune and metabolic profiling in a cohort of JSLE patients and age and gender matched healthy donors (HCs).

Methods:

Flow cytometry was carried out using two 15-colour panels to immune-phenotype peripheral blood mononuclear cells from 39 healthy donors (HCs, 17 male, 22 female, mean age 18) and 35 JSLE patients (12 male, 23 female, mean age 19). Data was analysed by cluster and phenotype–phenotype correlation. Flow cytometry was also used to measure functional and metabolic marker expression on immune cell subsets. Data was correlated with clinical assessments of disease.

Results:

Patients with JSLE were characterised by increased naïve and decreased memory B-cell and T-cell subsets and increased monocyte frequency (p=0.0013) compared to HCs. Furthermore, phenotype-phenotype correlation analysis identified differential associations between naïve and memory immune cell subtypes when comparing the HC and JSLE cohorts.

CD4+ and CD8+ T-cells from JSLE patients had elevated membrane lipid raft (p=0.0185, p=0.0087) and glucose transport receptor (GLUT-1) (p=0.0205, p=0.0017) expression suggesting that they were more metabolically active. Metabolic defects were also found in monocytes and plasmacytoid dendritic cells. The expression of these metabolic markers on different subsets correlated with cell frequency suggesting a role of cell metabolism in driving the JSLE phenotype. Furthermore the metabolic immune-phenotype in JSLE correlated positively with disease activity, erythrocyte sedimentation rate and dsDNA titre and negatively with complement protein C3 supporting the hypothesis that altered metabolism is associated with JSLE development and severity.

Unsupervised hierarchical cluster analysis of patient clinical data revealed that JSLE patients in this cohort could be stratified into 5 groups each with a unique clinical identity mainly associated with disease activity markers and the presence of anti-cardiolipin antibodies. Each group had a unique immune-phenotype and metabolic profile.

Conclusion:

Differences in the metabolic profiles of immune cell subsets in JSLE contribute to disease pathogenesis and severity. Cellular metabolic regulators may therefore have therapeutic benefit for JSLE patients. Defining these patient groups further may help to determine the therapeutic benefit of these and other therapeutics and allow for the treatment patients in a more effective and personalised manner.


Disclosure: G. Robinson, None; M. Adriani, None; I. Pineda Torra, None; Y. Ioannou, None; E. Jury, None.

To cite this abstract in AMA style:

Robinson G, Adriani M, Pineda Torra I, Ioannou Y, Jury E. Using Immune and Metabolic Phenotyping to Understand the Immunopathogenesis of Juvenile-Onset SLE and Stratify Patient Groups [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/using-immune-and-metabolic-phenotyping-to-understand-the-immunopathogenesis-of-juvenile-onset-sle-and-stratify-patient-groups/. Accessed August 12, 2022.
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