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

Abstract

Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities

“…However, the efficacy of L-T4 supplementation among euthyroid women applied to prevent miscarriage and preterm birth induced by HT in recent research is inconsistent ( Figure 1 B ). Notably, with the extended exploration of HT in recent years, an abnormally activated proinflammatory state of the immune system is found in these patients 14 , 17 , 18 , 33 - 35 . Therefore, these findings enrich our knowledge of HT-related miscarriage, especially in euthyroid women.…”

“…Although HT is regarded as one of organspecific autoimmune diseases (ADs), numerous clinical studies have confirmed that similar to other ADs, HT plays a vital role in women's miscarriage and even RM [9][10][11][12][13]. With the development of cellular and molecular immunology, accumulating studies have found that not only hypothyroidism but also immune system disorders [14] caused by HT conditions are involved in the pathogenesis of…”

“…Although HT is regarded as one of organ-specific autoimmune diseases (ADs), numerous clinical studies have confirmed that similar to other ADs, HT plays a vital role in women's miscarriage and even RM 9 - 13 . With the development of cellular and molecular immunology, accumulating studies have found that not only hypothyroidism but also immune system disorders 14 caused by HT conditions are involved in the pathogenesis of adverse pregnancy outcomes 15 - 18 . During a healthy pregnancy, the upregulation of regulatory T (Treg) cells and T-helper type 2 (Th2) cells represent a major maternal adaptation that helps with embryo implantation and the maintenance of pregnancy 19 - 21 .…”

The prospects of single‐cell analysis in autoimmunity

“…Furthermore, the power of mass cytometry has recently been applied to dissect immune dysfunction in a pilot study including patients with different endocrine autoimmune disorders. 58 Diverging immunological mechanisms in a single autoimmune disease is common and needs to be characterized precisely for better understanding of disease pathogenesis. Recent studies have used CyTOF to characterize the immune system in autoimmune T1D, 59 SLE 60 and RA, 61,62 but very few studies have focused on autoimmune endocrine diseases.…”

“…Viral infections have indeed been suggested to take part in the pathogenesis of autoimmune disease, 14 highlighting the importance of studying early changes during viral infections. Furthermore, the power of mass cytometry has recently been applied to dissect immune dysfunction in a pilot study including patients with different endocrine autoimmune disorders 58 . Diverging immunological mechanisms in a single autoimmune disease is common and needs to be characterized precisely for better understanding of disease pathogenesis.…”