MD-PhD Student Duke-NUS Medical School/Translational Immunology Institute Singapore, Singapore
Abstract Text: Systemic lupus erythematosus (SLE) is an autoimmune disease with unpredictable disease course due to alternating remissions and flares. Mechanistic insights are required for better assessment. To achieve this, SLE is best interrogated with a multi-parametric, holistic approach such as mass cytometry (CyTOF).
Peripheral blood mononuclear cells (PBMCs) from 26 SLE subjects (41 samples, median age 39.5years) and 27 age-matched subjects underwent CyTOF. Data was analysed and visualised using our laboratory-designed machine learning tool.
An activated CD8+CXCR3+CLA+ T-cell subset (CD8+CD45RA+CD38+CLA+CXCR3+) was enriched in SLE (median: 0.19%,interquartile range: 0.13-0.35% of CD45+ PBMCs) versus healthy (0.08%,0.05-0.09%; p< 0.0001). CXCR3 and cutaneous lymphocyte-associated antigen (CLA) are involved in skin-homing, with CLA function enhanced in inflammatory dermatoses. This suggests the importance of skin involvement in SLE immunopathogenesis even if skin manifestations are absent. Further analysis of the CD3+ cell compartment revealed unchanged natural T-regulatory cells (TREGS) between healthy and disease while some TREG-like populations (FoxP3+CD25-) are significantly increased in disease, highlighting a deranged TREG-driven immunoregulatory response. Thirdly, an activated CD8+BAFF+ T-cell subset (CD8+CD45RA+iCOS+ BAFF+) is enriched in SLE (0.975%,0.433-1.53%) versus healthy (0.28%,0.1-0.49%; p< 0.0001). B-cell activating factor (BAFF) supports autoreactive B cell survival in autoimmune disease; an anti-BAFF drug (belimumab) is FDA-approved for SLE. Despite increasing use of belimumab, not all patients respond equally, so BAFF inhibition alone may not adequately alter disease activity. Studying these cell subset interactions in detail to identify pathological pathways may facilitate improvements in current SLE theragnostics.
With a multi-parametric unbiased approach, we identified immune subsets of immunopathogenic importance for further studies.
