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High-dimensional immunophenotyping reveals immune cell aberrations in patients with undiagnosed inflammatory and autoimmune diseases
Alisa A. Mueller, … , James A. Lederer, Deepak A. Rao
Alisa A. Mueller, … , James A. Lederer, Deepak A. Rao
Published October 24, 2023
Citation Information: J Clin Invest. 2023;133(24):e169619. https://doi.org/10.1172/JCI169619.
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Research Letter Autoimmunity Inflammation Article has an altmetric score of 15

High-dimensional immunophenotyping reveals immune cell aberrations in patients with undiagnosed inflammatory and autoimmune diseases

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Abstract

Authors

Alisa A. Mueller, Takanori Sasaki, Joshua W. Keegan, Jennifer P. Nguyen, Alec Griffith, Alice M. Horisberger, Thomas Licata, Elizabeth Fieg, Ye Cao, Mehreen Elahee, Kathryne E. Marks, Daimon P. Simmons, Lauren C. Briere, Laurel A. Cobban, J. Carl Pallais, Frances A. High, Melissa A. Walker, Jenny J. Linnoila, Jeffrey A. Sparks, V. Michael Holers, Karen H. Costenbader, Undiagnosed Diseases Network, David A. Sweetser, Joel B. Krier, Joseph Loscalzo, James A. Lederer, Deepak A. Rao

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Figure 1

Mass cytometric profiling reveals outlier immune aberrations in undiagnosed patients and dysfunctional Treg expansion in a patient with inflammatory skin disease.

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Mass cytometric profiling reveals outlier immune aberrations in undiagno...
(A) UMAP of major immune cell populations identified in clustering analyses of mass cytometry T cell marker panel data. (B and C) For 16 UDN and 142 comparator patients, the cluster frequency as a proportion of total PBMCs (B) or the indicated cell populations (C). Red, clusters with an outlier. (D) UMAP of outlier cluster (arrow) from UDN no. 1. (E and F) Bar chart (E) and biaxial gating plot (F) showing frequency of the outlier cluster as a proportion of total T cells for UDN no. 1. (G) Photographs depicting alopecia and erythroderma in UDN no. 1. (H) H&E and immunofluorescence microscopy of skin biopsies from UDN no. 1; green, CD25; red, FoxP3. Scale bar, 50 µm. (I) UMAP of scRNA-Seq data of CD4+ T cell populations from patients with RA (n=28) and UDN no. 1 (top). UMAP of CD4+ T cell population for UDN no. 1 alone at 3 time points (bottom). Arrows indicate Tregs. (J) Top pathways enriched in Tregs from UDN no. 1 compared to patients with RA (n=28). (K) Quantification of suppression of CD4+ T cell proliferation by Tregs from controls (n=3), patients with RA (n=3), and UDN no. 1. Mean and SD are shown. (L) Violin plots illustrating IFN signaling and activation scores in Tregs from UDN no. 1 at enrollment, after CTLA4-Ig therapy, and after JAK inhibitor therapy.

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