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.
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 June 1, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-pathway-activation-in-t-follicular-helper-tfh-cell-subsets-in-human-myositis/