ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 75

Microglia-Specific Transcriptional Signatures Correlate with Behavioral Deficits in ‘Neuropsychiatric Symptoms of Systemic Lupus Erythematosus’

Hadijat Makinde1, Elise Mike 2, Chaim Putterman 3, Deborah Winter 4 and Carla Cuda 5, 1Northwestern University, Chicago, IL, 2Albert Einstein College of Medicine, Bronx, NY, 3Albert Einstein College of Medicine, New York, NY, 4Northwestern University Feinberg School of Medicine, Division of Rheumatology, Chicago, 5Northwestern University Feinberg School of Medicine, Division of Rheumatology, Chicago, IL

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: innate immunity, Macrophage, neurologic involvement and animal models, Systemic lupus erythematosus (SLE)

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Sunday, November 10, 2019

Session Title: SLE – Animal Models Poster

Session Type: Poster Session (Sunday)

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

Background/Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome affecting multiple organs, including the brain. More than 50% of patients experience neuropsychiatric symptoms of SLE (NPSLE) that often occur early in disease and go undiagnosed. Despite the devastating impact of NPSLE on health-related quality of life, underlying disease mechanisms are unknown. Microglia are the resident innate immune cells of the brain; accumulating evidence points to microglia as drivers of neurological conditions ranging from neurodevelopmental (autism) to neurodegenerative (Alzheimer’s disease, chronic pain) disorders. The recently discovered disease-associated microglia (DAM) subset is enriched for lipid metabolism pathways and phagocytosis-related functions. The vast majority of investigations into microglia, particularly DAM, have occurred in neurodegenerative disease models of Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis. However, very few studies have examined microglia, particularly DAM, in the context of NPSLE. Here, we probed microglia from two NPSLE-prone mouse strains at the transcriptional level to potentially correlate gene signatures with behavioral deficits.

Methods: Mice with caspase 8 flanked by loxP sites (Casp8fl/fl, WT) were bred to mice expressing Cre under the CD11c gene promoter to generate CReCOM (Caspase-8 Removed CD11c-specific Overactive MyD88) mice. B6.Sle1.Sle3 mice were derived from the introgression of 2 NZM2410-derived susceptibility loci onto non-autoimmune C57BL/6 (B6) mice. 3-4 month old WT and CReCOM mice underwent behavioral testing. Microglia were sorted from mice following behavioral tasks and from 10-12 month old WT, CReCOM, B6 and B6.Sle1.Sle3 mice for RNA-seq analysis (n=4/group).

Results: CReCOM mice develop an inflammatory disease reminiscent of human SLE and exhibit significant impairment in spatial memory, contextual associative learning, startle response and motor coordination, similar to patients with NPSLE. Likewise, the recently validated B6.Sle1Sle3 NPSLE model exhibits depression-like behavior and significant impairment in spatial and recognition memory, symptoms detected in NPSLE patients. Of the significantly upregulated genes (DESeq2, p< 0.05, fold change in expression >1.5) observed in CReCOM (256) and B6.Sle1.Sle3 (214) microglia compared to their respective controls, a common 18-gene ‘NPSLE signature’ is shared (p< 2.54×10-4) and enriched for genes associated with lipid metabolism, scavenger receptor activity and downregulating inflammatory responses and cell chemotaxis processes. NPSLE microglia are also enriched for genes associated with the DAM subset. Moreover, microglial expression of ‘NPSLE’ and ‘DAM’ signatures significantly correlate with the severity of behavioral deficits in CReCOM mice.

Conclusion: The discovery of our novel ‘NPSLE signature’, as well as enrichment of the ‘DAM signature’, represents the first to connect microglia-specific transcriptional signatures with clinical outcomes in NPSLE-like disease. In future studies, we will assess the penetrance of these signatures to further interrogate how defective microglial function may incite NPSLE.


Disclosure: H. Makinde, None; E. Mike, None; C. Putterman, Equillium, 5, Equillium, Inc, 2, 5, Exagen, 2; D. Winter, None; C. Cuda, None.

To cite this abstract in AMA style:

Makinde H, Mike E, Putterman C, Winter D, Cuda C. Microglia-Specific Transcriptional Signatures Correlate with Behavioral Deficits in ‘Neuropsychiatric Symptoms of Systemic Lupus Erythematosus’ [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/microglia-specific-transcriptional-signatures-correlate-with-behavioral-deficits-in-neuropsychiatric-symptoms-of-systemic-lupus-erythematosus/. Accessed April 17, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/microglia-specific-transcriptional-signatures-correlate-with-behavioral-deficits-in-neuropsychiatric-symptoms-of-systemic-lupus-erythematosus/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.