ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0994

Role of SLE Associated Cytokines in Generation of Mature Neutrophils

Neelakshi R. Jog, Julia Nguyen and Judith James, Oklahoma Medical Research Foundation, Oklahoma City, OK

Meeting: ACR Convergence 2021

Keywords: neutrophils, Systemic lupus erythematosus (SLE)

  • Tweet
  • Email
  • Print
Session Information

Date: Monday, November 8, 2021

Title: Innate Immunity Poster (0992–1006)

Session Type: Poster Session C

Session Time: 8:30AM-10:30AM

Background/Purpose: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoantibody production and periods of elevated disease activity. Recent studies indicate that along with dysfunctional adaptive immune responses, neutrophils are also important in disease pathogenesis. SLE patients have higher numbers of low-density granulocytes (LDGs) in peripheral blood that express neutrophil markers and are hyper-responsive to external stimuli. LDGs are suggested to be pathogenic in lupus. However, the mechanisms leading to increased LDGs in SLE patients are unclear.

Methods: Peripheral blood mononuclear cells from 19 SLE patients with varying disease activity and 11 controls were enriched by density gradient centrifugation. LDG numbers were determined by flow cytometry. Plasma cytokines were measured by xMAP assays. Induced pluripotent stem cells (iPSC) derived from adult peripheral blood CD34+ cells were differentiated into neutrophils using feeder-culture conditions. Cultures were supplemented with IL-13 at different stages of differentiation: day 7 (hemangioblasts-like cells to CD34+ hematopoietic stem cells (HSC)), day 12 (HSC into CD45+ hematopoietic cells), day 18 (CD45+ cells into neutrophil precursors), day 23 (maturation to segmented neutrophils).

Results: SLE patients with elevated disease activity had significantly higher frequency of immature LDGs as determined by surface marker expression (p=0.005). IL-13 levels were higher in SLE patients with elevated disease activity compared to low disease activity patients (p=0.01) and controls (p=0.006), and the levels correlated negatively with absolute neutrophil numbers (r = -0.4404, p= 0.0354). Our goal was to test whether abnormal timing and excessive IL-13 exposure of hematopoietic stem cells (HSC) leads to generation of immature neutrophils in SLE patients due to defective differentiation. The iPSC cultures were induced into neutrophilic differentiation. By day 23 of differentiation, presence of IL-13 reduced frequencies of neutrophilic cells. The presence of IL-13 did not inhibit early stages of neutrophil differentiation. However, the frequencies of more mature band and segmented cells was significantly reduced when exposed to IL-13 at day 7. In the cultures where IL-13 supplementation was started at day 18 and day 23, neutrophils were generated when allowed to differentiate for a longer duration (Fig 1). Thus, although delayed, maturation was restored with late IL-13 exposure. Although IL-13 inhibited neutrophilic differentiation, it did not affect the generation of CD34+ HSC or CD45+ cells.

Conclusion: Our data suggest that SLE patients may have dysregulated development of myeloid cells in the bone marrow due to the cytokine milieu during elevated disease activity. Abnormal timing and exposure to IL-13 may increase immature neutrophils in SLE patients, possibly by altering the differentiation potential of CD34+ HSC. The functional responses of these newly generated neutrophils may differ due to differences in the bone marrow transit time. The dysregulation of granulopoiesis therefore may generate neutrophils that further exacerbate autoimmune response.

Figure 1.
Early IL_13 exposure inhibits neutrophil differentiation. CD45+cells from day 23 of iPSC differentiation were allowed to mature into neutrophils additional 17 days. A. Flow cytometry was performed on day 9 (Day 23+9) and 17 (Day 23+17). Percent of mature neutrophils are shown. B. Giemsa staining on cytospins of differentiating cells. Days are the day of differentiation IL_13 supplementation was started.


Disclosures: N. Jog, None; J. Nguyen, None; J. James, Progentec Diagnostics, Inc., 2.

To cite this abstract in AMA style:

Jog N, Nguyen J, James J. Role of SLE Associated Cytokines in Generation of Mature Neutrophils [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/role-of-sle-associated-cytokines-in-generation-of-mature-neutrophils/. Accessed .
  • Tweet
  • Email
  • Print

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-sle-associated-cytokines-in-generation-of-mature-neutrophils/

Advanced Search

Your Favorites

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

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology