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Poster Session B

Systemic lupus erythematosus (SLE)

Session: (0899–0933) SLE – Etiology & Pathogenesis Poster

0924: Distinct Cell-Bound Complement Activation Products Associate with Disease Activity and Immune Transcriptional Signatures in SLE

Monday, November 13, 2023
9:00 AM – 11:00 AM PT
Location: Poster Hall
On Demand In Person

    Abstract Poster Presenter(s)

  • Alfred Kim, MD, PhD (he/him/his)

    Washington University School of Medicine
    St. Louis, MO, United States

    Disclosure(s): ANI Pharmaceuticals: Consultant (Terminated, July 31, 2022); AstraZeneca: Consultant (Ongoing), Grant/Research Support (Ongoing); Aurinia Pharmaceuticals: Consultant (Ongoing); Exagen Diagnostics: Consultant (Ongoing), Speaker/Honoraria (includes speakers bureau, symposia, and expert witness) (Ongoing); GlaxoSmithKlein(GSK): Consultant (Ongoing), Grant/Research Support (Ongoing), Speaker/Honoraria (includes speakers bureau, symposia, and expert witness) (Ongoing); Kypha Inc: Consultant (Ongoing), Intellectual Property/Patents (Ongoing); Novartis: Grant/Research Support (Ongoing); Pfizer: Consultant (Terminated, April 30, 2022)

Gabriel Arguelles, Lynne Mitchell, Dennis Hourcade, John Atkinson, Elisha Roberson and Alfred Kim, Washington University School of Medicine, St. Louis, MO

Background/Purpose: Complement plays a central role in SLE, generating an array of bioactive soluble and cell-bound complement activation products (CB-CAPs) during disease activity. Data are lacking though detailing the types, quantities, and impacts of the numerous CB-CAP on SLE immune cells, especially with respect to disease activity. We applied a mass cytometry (MC) panel that can detect over 20 CB-CAPs and complement receptors to PBMCs from paired flare and remission samples from 6 patients with classified SLE. Furthermore, we analyzed single-cell transcriptional profiles on flaring samples using antibodies to the most prevalent CB-CAPs using cellular indexing of transcriptomes and epitopes (CITE)-seq.

Methods: Adults with ACR- or SLICC-classified SLE (n=6) were consented for PBMC collection at Washington University School of Medicine. Isolated PBMCs were subjected to single cell MC and CITE-seq (n=3). MC data analysis was performed with Cytobank. CITE-seq data analyses was performed with Seuret, gProfileR, and Comprehensive Multi-omics Platform for Biological InterpretatiOn (COMPBIO).

Results: We found the highest frequency of C4d, C3d, C5, and Bb deposition on B cells compared to T cells and monocytes during SLE flares (Fig 1). During disease remission, low levels of all CB-CAPs were observed in these cells. Compared to controls, transitional B cells from flaring patients with SLE had high levels of C5 and Bb with little C4d or C3d (Fig 2). CD11c+ B cells from flaring patients also had elevated Bb deposition compared to controls. CITE-seq transcriptional profiling identified Bb- and C3d-bearing CD11c+ B cells possessing a type I interferon signature, with Bb-bearing B cells further possessing a TNF/NF-κB transcriptional signature.

Conclusion: A high level of CB-CAP deposition was observed in B cells obtained from flaring subjects with a SLE, which was absent during disease remission. The types of CB-CAPs found on PBMCs were not uniform between cell types, potentially opening a previously undescribed heterogeneity in SLE. Additional heterogeneity was observed in the transcriptional profiles associated with specific CB-CAPs on B cells. These pilot data demonstrate the feasibility of the MC complement panel on human samples, and the potential insights CITE-seq has using CB-CAPs in discovering novel mechanisms of complement activation and regulation.


Fig 1. Mass cytometry of CB-CAP deposition on PBMCs from paired flaring and remission patients with SLE, along with matched controls.


Fig 2. Mass cytometry of of CB-CAP deposition on B cell subsets from flaring patients with SLE versus matched controls.


G. Arguelles: None; L. Mitchell: None; D. Hourcade: None; J. Atkinson: Alexion Pharmaceuticals, 2, Alnylam Pharmaceuticals, 2, Celldex Therapeutics, 2, Genentech, 2, Idera Pharmaceuticals, 2, Kereos Inc, 2; E. Roberson: None; A. Kim: ANI Pharmaceuticals, 2, AstraZeneca, 2, 5, Aurinia Pharmaceuticals, 2, Exagen Diagnostics, 2, 6, GlaxoSmithKlein(GSK), 2, 5, 6, Kypha Inc, 2, 10, Novartis, 5, Pfizer, 2.