ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0715

High-Dimensional Analysis Reveals Abnormal B Cell Subsets Associated with Specific Changes to Circulating T and Myeloid Cell Populations in Patients with Idiopathic Inflammatory Myopathies

Erin Wilfong1, Todd Bartkowiak2, Katherine Vowell1, Camille Westlake1, Jonathan Irish2, Peggy Kendall3, Leslie Crofford1 and Rachel Bonami1, 1Vanderbilt University Medical Center, Nashville, TN, 2Vanderbilt University, Nashville, TN, 3Washington University in St. Louis, St. Louis, MO

Meeting: ACR Convergence 2021

Keywords:

Session Information

Date: Sunday, November 7, 2021

Title: Muscle Biology, Myositis & Myopathies Poster (0683–0722)

Session Type: Poster Session B

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

Background/Purpose: The idiopathic inflammatory myopathies (IIM) are a clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. This study aims to investigate the immunologic heterogeneity through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients and healthy controls.

Methods: We collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis in the inpatient or outpatient setting and 18 healthy controls. Immunophenotyping was performed using mass cytometry by time of flight (CyTOF) to simultaneously characterize B, T, and myeloid cell subsets. Data were analyzed using a combination of supervised biaxial gating and unsupervised clustering algorithms including t-distributed stochastic neighbor embedding (tSNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM).

Results: Patient demographics are shown in Table 1. We identified two distinct immune signatures amongst IIM patients (Figure 1). In one signature, increased CD19+CXCR4hiCCR7hi cells correlated with increased CD3+CXCR4hiCD38hi (Spearman r=0.62, p=0.009) and CD14+CD16-CXCR4+CD38+HLADR- (Spearman r=0.61, p=0.01) populations. Three out of five patients with a significant CD19+CXCR4hiCCR7hi island were critically ill with respiratory failure, a fourth was admitted with inability to swallow. In the second signature, increased CD19+CD21loCD11c+ cells correlated with an increased CD3+CD4+PD1+ (Spearman r=0.60, p=0.01) population. Of the six patients with a dominant CD19+CD21loCD11c+ island, four were Pm/Scl positive.

Conclusion: Based on circulating B cell phenotype, we identified two distinct immunologic signatures in IIM patients. Future work is needed to determine the significance of these immune signatures for clinical manifestations and treatment responses.

Disclosures: E. Wilfong, Boehringer-Ingelheim, 1, 5; T. Bartkowiak, None; K. Vowell, GSK, 3; C. Westlake, None; J. Irish, Incyte Corporation, 5, Janssen, 5, Pharmacyclics, 5, Kadmon, 5, Fluidigm, 12, Center of Excellence Agreement via Vanerbilt's Mass Cytometry Center of Excellence Core, Cytobank, 4, 11; P. Kendall, None; L. Crofford, Boehringer-Ingelheim, 5, UpToDate, 9; R. Bonami, Boehringer-Ingelheim, 5.

To cite this abstract in AMA style:

Wilfong E, Bartkowiak T, Vowell K, Westlake C, Irish J, Kendall P, Crofford L, Bonami R. High-Dimensional Analysis Reveals Abnormal B Cell Subsets Associated with Specific Changes to Circulating T and Myeloid Cell Populations in Patients with Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/high-dimensional-analysis-reveals-abnormal-b-cell-subsets-associated-with-specific-changes-to-circulating-t-and-myeloid-cell-populations-in-patients-with-idiopathic-inflammatory-myopathies/. Accessed .

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