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Abstract Number: 93

Interferon Pathway Activation in T Follicular Helper (Tfh) Cell Subsets in Human Myositis

Amrutesh Puranik1, Mark Jensen 2, Regine Tipon 3, Yogita Ghodke-Puranik 3, Valeria Mezzano 4, Shanmugapriya Selvaraj 5, Theresa Wampler Muskardin 4, Cynthia Loomis 4, Ann Reed 6, Lauren Pachman 7 and Timothy Niewold 5, 1NYU Langone Health, New York, NY, 2Colton Center for Autoimmunity, NYU School of Medicine, New York, NY, 3Colton Center for Autoimmunity, NYU School of Medicine, New York, 4New York University Langone Health, New York, 5New York University Langone Health, New York, NY, 6Duke University School of Medicine, Durham, NC, 7Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: autoimmune diseases and interferons, dermatomyositis, juvenile dermatomyositis

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Session Information

Date: Sunday, November 10, 2019

Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: T and B cells come together in ectopic lymphoid aggregates in myositis, suggesting that local T:B cell interactions could play a role in disease.  T follicular helper cells are increased in circulation in patients with active myositis.  We studied circulating Tfh cells from myositis patients using single-cell RNA-sequencing and examined the proximity of Tfh cells to B cells in patient biopsies.

Methods: Tfh cells [CD3+CXCR5+PD-1+CXCR3neg and CD3+CXCR5+PD-1+CXCR3pos] cells were sorted from peripheral blood and subsets were identified by chemokine markers to designate Tfh1 and Tfh2/17 cell subsets.  RNA sequencing was performed on individual cells of (3 controls and 3 myositis patients) using Fluidigm C1 HT platform, and data were analyzed using a pseudo-temporal ordering using Monocle.  Biopsies were stained using the OPAL standardized sequential immunofluorescence method for PD-1, CXCR5, CD19, and CD4 in human muscle, and machine learning was used to map proximity of B cells to all T-cells compared with Tfh cells.

Results: We found various subsets within the Tfh pool, corresponding to Tfh1 and Tfh2/17 cells and some cells that looked to be transitioning between states.  Tfh2/17 were enriched in myositis patients vs. controls.  The Tfh2/17 cells demonstrated a type I interferon signature, while the Tfh1 cells had a type II interferon and proteasome signature.  In tissue, we demonstrate Tfh cells in close proximity to B cells in lymphoid aggregates.

Conclusion: Tfh cells are present in myositis biopsies juxtaposed to B cells, suggesting productive T:B interactions in the tissue.  Tfh subsets in blood from patients demonstrate distinct pathological signatures when compared to controls.


Disclosure: A. Puranik, None; M. Jensen, None; R. Tipon, None; Y. Ghodke-Puranik, None; V. Mezzano, None; S. Selvaraj, None; T. Wampler Muskardin, None; C. Loomis, None; A. Reed, None; L. Pachman, None; T. Niewold, None.

To cite this abstract in AMA style:

Puranik A, Jensen M, Tipon R, Ghodke-Puranik Y, Mezzano V, Selvaraj S, Wampler Muskardin T, Loomis C, Reed A, Pachman L, Niewold T. Interferon Pathway Activation in T Follicular Helper (Tfh) Cell Subsets in Human Myositis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/interferon-pathway-activation-in-t-follicular-helper-tfh-cell-subsets-in-human-myositis/. Accessed .
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