Background/Purpose: Cell-bound complement activation products (CB-CAPs) have previously been shown to associate with SLE disease activity, but only a small fraction of total CB-CAPs has been examined. Leveraging mass cytometry, we have developed and validated a panel capable of comprehensively characterizing the types and quantities of CB-CAPs and complement receptors on human PBMCs. In this pilot study, we sought to characterize the types and amounts of CB-CAPs observed in flaring and inactive SLE and identify SLE patient stratifications based on CB-CAPs signatures.

Methods: Six paired PBMC samples from flaring and remission consented patients with 1997 ACR or 2012 SLICC classified SLE were obtained from the Washington University Lupus Clinic. Mass-tag barcoded PBMCs were stained using a validated set of 30 antibodies to cell surface markers, various CB-CAPs, and complement receptors. Stained PBMCs were run on a Helios-upgraded CyTOF2 mass cytometer, and data analyzed in Cytobank (viSNE, FlowSOM).

Results: We found that in flaring subjects, B cells possessed the greatest load of CB-CAPs compared to T cell and macrophages. Most CB-CAPs markers were absent in the paired remission samples. Evidence of classical, alternative, and common pathway activation was observed on these SLE B cells and can be categorized into six broad metaclusters. Five of the metaclusters possessed both classical and alternative pathway activation markers but differed in how completely the common pathway was activated, including 25% of B cells that did not activate C5 at all despite C3 activation. The fifth metacluster possessed only alternative and common pathway activation markers. B cell subsets of virtually every type could be found in each metacluster, with the exception of plasma cells which were devoid of any complement activation markers.

Conclusion: These data represent the first attempt to stratify SLE patients based off of CB-CAP signatures. B cells from flaring subjects broadly possess CB-CAPs, and all B cell subsets with exception of plasma cells are subject to complement activation. Subjects in remission were essentially devoid of CB-CAPs. We observed six distinct CB-CAPs signatures, with differences in the extent of classical, alternative, and common pathway activation defining these signatures. Our data may have important implications for how CB-CAPs biomarkers are best used in the clinic and clinical trials. Additionally, identification of CAPS signatures may inform investigators about which complement targets are best suited for specific individuals.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-cell-bound-complement-activation-signatures-are-observed-in-patients-with-systemic-lupus-erythematosus/