Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome

Abstract

Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune‐cells in 169 patients with these SADs and 44 healty controls (HC) using mass‐cytometry and assessed the diagnostic value of these results. Alterations in the frequency of immune‐cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56hi NK‐cells in SSc and IgM+ Bcells in pSS, were disease specific; only a reduced frequency of plasmacytoid dendritic cells was common between all SADs Strikingly, hierarchical clustering of SSc patients identified 4 clusters associated with different clinical phenotypes, and 9 of the 12 cell subset‐alterations in SSc were also present during the preclinical‐phase of the disease. Additionally, we found a strong association between the use of prednisone and alterations in B‐cell subsets. Although differences in immune‐cell frequencies between these SADs are apparent, the discriminative value thereof is too low for diagnostic purposes. Within each disease, mass cytometry analyses revealed distinct patterns between endophenotypes. Given the lack of tools enabling early diagnosis of SSc, our results justify further research into the value of cellular phenotyping as a diagnostic aid.

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

“…Additionally, a linear increase in activated CD56 bright NK cells with SSc progression from early to definite SSc was demonstrated following TLR1/2 stimulation, highlighting the contribution of NK cells to SSc onset (95). NK cells secrete cytokines such as TNF-α, IL-6, and macrophage inflammatory protein (MIP)-1α and crosstalk with other immune cell types including DCs in response to TLR stimulation, thereby aggravating inflammation (96). Although the number of circulating NK cells is preserved in SSc, the cells show an unusual phenotype with decreased expression of chemokine receptors [CX3C chemokine receptor (CX3CR)1 and CXCR4], NKG2D, and CD69 (92).…”

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

“…Mass cytometry is a high-dimensional single-cell technology that enables simultaneous characterization of the immune system, which has yielded novel information about T1D (18)(19)(20), systemic lupus erythematous (21) and rheumatoid arthritis (22). A limited number of studies have used this approach to compare different diseases in parallel (23,24), but none have focused on immunological features in patients with autoimmune endocrine diseases. In our study, we used mass cytometry to perform a deep characterization and simultaneous comparison of PBMC from patients with T1D, HT, GD, and AD.…”

Novel Technologies in Studying Brain Immune Response

“…Thus, if few cells are isolated by FACS, SCRB-seq, MARS-seq, or Smartseq2 protocols may be desirable. [57], and systemic autoimmune diseases [58], deepening our understanding of cell biology and human diseases. Recently, this leading technology has been applied to characterize the brain immune system.…”