Longitudinal Immune Cell Profiling in Patients With Early Systemic Lupus Erythematosus

Abstract

Objectives To investigate the immune cell profiles of patients with systemic lupus erythematosus (SLE), and to identify longitudinal changes in those profiles over time. Methods We employed mass cytometry with 3 different panels of 38–39 markers (an immunophenotyping panel, a T cell/monocyte panel, and a B cell panel) in cryopreserved peripheral blood mononuclear cells (PBMCs) from 9 patients with early SLE, 15 patients with established SLE, and 14 controls without autoimmune disease. We used machine learning–driven clustering, flow self‐organizing maps, and dimensional reduction with t‐distributed stochastic neighbor embedding to identify unique cell populations in early SLE and established SLE. We used mass cytometry data of PBMCs from 19 patients with early rheumatoid arthritis (RA) and 23 controls to compare levels of specific cell populations in early RA and SLE. For the 9 patients with early SLE, longitudinal mass cytometry analysis was applied to PBMCs at enrollment, 6 months after enrollment, and 1 year after enrollment. Serum samples were also assayed for 65 cytokines using Luminex multiplex assay, and associations between cell types and cytokines/chemokines were assessed. Results Levels of peripheral helper T cells, follicular helper T (Tfh) cells, and several Ki‐67+ proliferating subsets (ICOS+Ki‐67+ CD8 T cells, Ki‐67+ regulatory T cells, CD19intermediateKi‐67high plasmablasts, and PU.1highKi‐67high monocytes) were increased in patients with early SLE, with more prominent alterations than were seen in patients with early RA. Longitudinal mass cytometry and multiplex serum cytokine assays of samples from patients with early SLE revealed that levels of Tfh cells and CXCL10 had decreased 1 year after enrollment. Levels of CXCL13 were positively correlated with levels of several of the expanded cell populations in early SLE. Conclusion Two major helper T cell subsets and unique Ki‐67+ proliferating immune cell subsets were expanded in patients in the early phase of SLE, and the immunologic features characteristic of early SLE evolved over time.

Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R

“…The analysis revealed that cT FH cells were expanded in the early phase of lupus and decreased longitudinally, while a recently described cell type, namely, peripheral T helper cells (T PH ), remained elevated during the first year post-enrollment. Their hypothesis was that T FH -B cell interactions in lymphoid tissues may be important at the onset of the disease, which may then be changed to T PH -B cell interplay at the site of inflammation in time [ 45 ]. Interestingly, when they measured the correlation between serum chemokine levels and immune cells, CCL20 was strongly correlated with expanded cT FH cells.…”

A new insight into the impact of systemic lupus erythematosus on oocyte and embryo development as well as female fertility

“…Ovarian inflammation and damage induced by part of autoantibodies can also lead to decreased ovarian reserve (DOR) or premature ovarian failure (POF) ( 36 ). Meanwhile, there was much evidence of immune imbalance in patients with SLE, such as regulatory T cell dysfunction ( 37 ) and abnormal production of multiple cytokines ( 38 ) which contributed to decreased ovarian reserve. In addition, a study evaluated the lymphocyte subpopulation in SLE patients.…”

Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets

“…The role of CD8 + T cells in SLE is gaining interest. Their cell numbers are increased in early lupus and are present in the interstitium of kidneys from patients with nephritis 201 202. The contribution of IFN-I to mechanisms of lupus pathogenesis may involve both CD4 + and CD8 + T cells, with IFN-I-stimulated genes expressed in both subsets, Tfh support for pathogenic B cell responses dependent on IFN-I in a STAT4-dependent manner, and IFN-I promoting altered mitochondrial function and lupus-like functional impairment in CD8 + T cells 203 204.…”