Autoimmune rheumatologic diseases

Poster

A Dual Immune Regulatory Mechanism Is Associated with Quiescent Disease in Juvenile Systemic Lupus Erythematosus

Friday, June 16
6:15 PM - 7:30 PM

Introduction:
Systemic Lupus Erythematosus (SLE) is a multi-factorial autoimmune disease and the conventional investigative approach involving one cell type at a time is inadequate for its study. The ability to interrogate different immune cell types simultaneously is a critical unmet need. We hypothesise that abnormalities within the immune-regulatory mechanism contributes to lupus pathogenesis. To address such unmet needs and hypotheses, we employed a multi-dimensional approach using mass cytometry to study the immunome of juvenile SLE (jSLE) patients.ÂÂ


Methods:
Peripheral blood mononuclear cells from 12 jSLE patients stratified clinically into active and inactive disease, were interrogated with mass cytometry and subsequent analysis done using an unbiased, unsupervised machine learning approach with dimensional reductions followed by automated cell classification, clustering and visualisation.ÂÂ


Results:
A statistically significant enrichment of T and B regulatory cells with high CXCR5 expression were found in inactive jSLE patients. CXCR5 is important as it can direct these regulatory cells to the lymph node germinal centre, a critical lupus related microenvironment. Secondly, distinct B cell differences exist with an absence of the IL10 secreting B regulatory cells and a lower expression of CD32B (an inhibitory immune receptor) associated with active disease.ÂÂ


Conclusion:
A dual regulatory mechanism, involving both the T and B regulatory cells, is significantly associated with lupus inactivity. In addition, dichotomisation of the B cells into two distinct signatures with the different disease states were also found, underpinning its potential for its utilisation as a predictor of clinical fate or future therapeutic target.ÂÂ

Joo Guan Yeo

SingHealth Translational Immunology and Inflammation Centre

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    Jing Yao Leong

    Research fellow
    SingHealth Translational Immunology and Inflammation Centre

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      Thaschawee Arkachaisri

      Senior Consultant and Head of Rheumatology and Immunology Service
      KK Women’s and Children’s Hospital and Duke-NUS Graduate Medical School Singapore

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        Xuesi Sim

        Student
        Singapore Polytechnic

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          Justin Tan

          Consultant, Rheumatology and Immunology Service
          KK Women’s and Children’s Hospital

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            Lena Das

            Consultant, Rheumatology and Immunology Service
            KK Women's and Children's Hospital

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              Loshinidevi D/O Thana Bathi

              SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

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                Phyllis Chen

                SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

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                  Salvatore Albani

                  Director
                  SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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                    A Dual Immune Regulatory Mechanism Is Associated with Quiescent Disease in Juvenile Systemic Lupus Erythematosus



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