Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells

Namita A Goyal; Gérald Coulis; Jorge Duarte; Philip K Farahat; Ali H Mannaa; Jonathan Cauchii; Tyler Irani; Nadia Araujo; Leo Wang; Marie Wencel; Vivian Li; Lishi Zhang; Steven A Greenberg; Tahseen Mozaffar; S Armando Villalta

doi:10.1212/WNL.0000000000200013

Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells

Neurology. 2022 Mar 29;98(13):e1374-e1383. doi: 10.1212/WNL.0000000000200013. Epub 2022 Feb 7.

Authors

Affiliations

¹ Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA.
² Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA. [email protected].

Abstract

Background and objectives: To evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1⁺) within the T and natural killer (NK) cell compartments.

Methods: Blood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1-4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56.

Results: We found that a population of KLRG1⁺ Tem and TemRA were expanded in both the CD4⁺ and CD8⁺ T-cell subpopulations in patients with IBM. KLRG1 expression in CD8⁺ T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56⁺CD8⁺ T cells. The frequency of KLRG1⁺ total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8⁺ T-cell differentiation.

Discussion: Our findings reveal that the selective expansion of blood KLRG1⁺ T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

CD8-Positive T-Lymphocytes*
Humans
Immunologic Memory
Immunophenotyping
Killer Cells, Natural / metabolism
Leukocytes, Mononuclear
Myositis, Inclusion Body*

Abstract

Publication types

MeSH terms

Grants and funding