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Abstract Number: 1711

CD14+ Monocytes Demonstrate a Unique Transcriptional Signature in Macrophage Activation Syndrome, Highlighting a Role for Interferons and Identifying Putative Hemophagocytes in Circulation

Susan Canny1, Hannah DeBerg2, Griffin Gessay2, Ailing Lu3, Mary Eckert4, Andrea La Bella5, Susan Shenoi6, Joyce Hui-Yuen7, Betsy Barnes8 and Jessica Hamerman2, 1Seattle Children's Hospital/University of Washington, Seattle, WA, 2Benaroya Research Institute, Seattle, WA, 3Feinstein Institutes for Medical Research, Manhasset, NY, 4Seattle Children's Hospital, Seattle, WA, 5Cohen Children's Medical Center, Queens, NY, 6Seattle Childrens Hospital, Mercer Island, WA, 7Division of Pediatric Rheumatology, Cohen Children's Medical Center, Lake Success, NY, 8Northwell Health, Manhasset, NY

Meeting: ACR Convergence 2023

Keywords: cytokines, Inflammation, macrophage activation syndrome

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Session Information

Date: Tuesday, November 14, 2023

Title: (1705–1712) Pediatric Rheumatology – Basic Science Poster

Session Type: Poster Session C

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

Background/Purpose: Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. MAS is characterized by a dysfunctional hyperinflammatory response in which there is abnormal activation of lymphocytes and phagocytes, leading to an overproduction of inflammatory cytokines and damage to host tissues. Circulating monocytes are highly responsive to their surrounding environment, are known to exhibit phenotypic and functional changes during inflammation, and can give rise to macrophages that phagocytose immune cells. However, monocytes and macrophages have not been well-studied in MAS. MAS is most commonly associated with systemic juvenile idiopathic arthritis (sJIA). At least 10% of sJIA patients will experience an overt episode of MAS with up to 50% exhibiting signs of subclinical inflammation.

Methods: We analyzed classical CD14+ monocytes from children with active MAS (6 subjects) compared to individuals with sJIA without MAS (4 subjects) and age/sex/race-matched healthy children (8 subjects) by flow cytometry and RNA sequencing (RNA-Seq). Seven MAS subjects and four age/sex/race-matched healthy controls were analyzed by single cell RNA sequencing (scRNA-Seq). Subjects with MAS were defined based on the 2016 classification criteria by Ravelli and colleagues as well as the ratio of ferritin to ESR.

Results: We found significant upregulation of CD16 surface expression during active MAS using flow cytometry (n=4-8 per group, p < 0.001). Our bulk RNA-Seq data show broad transcriptional changes in CD14+ monocytes from children with active MAS, including upregulation of RNase 2 (involved in processing RNAs for the innate immune sensor TLR8) and SLAMF7 (associated with monocyte/macrophage hyperinflammation in response to interferon gamma). scRNA-Seq analyses of myeloid cells from subjects with active MAS revealed a strong interferon signature in MAS monocytes with enrichment of interferon stimulated genes and alarmins. We identified hemoglobin transcripts in monocytes cells from MAS subjects by scRNA-Seq. Cells containing hemoglobin transcripts were also enriched for platelet associated genes (PF4, PPBP, GP9) and genes involved in motility, suggesting the detection of hemophagocytes in circulation.

Conclusion: These data confirm an important role for cytokines, specifically interferons, in driving gene expression in monocytes during MAS and suggest potential targets for future therapies. Together, our data show that CD14+ monocytes have a unique transcriptional signature in MAS and identify putative hemophagocytes in circulation during MAS.


Disclosures: S. Canny: None; H. DeBerg: None; G. Gessay: None; A. Lu: None; M. Eckert: None; A. La Bella: None; S. Shenoi: None; J. Hui-Yuen: None; B. Barnes: None; J. Hamerman: None.

To cite this abstract in AMA style:

Canny S, DeBerg H, Gessay G, Lu A, Eckert M, La Bella A, Shenoi S, Hui-Yuen J, Barnes B, Hamerman J. CD14+ Monocytes Demonstrate a Unique Transcriptional Signature in Macrophage Activation Syndrome, Highlighting a Role for Interferons and Identifying Putative Hemophagocytes in Circulation [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/cd14-monocytes-demonstrate-a-unique-transcriptional-signature-in-macrophage-activation-syndrome-highlighting-a-role-for-interferons-and-identifying-putative-hemophagocytes-in-circulation/. Accessed .
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