Dysregulation of Peripheral Blood B Cells and Natural Killer Cells Is Associated With Myocarditis in Idiopathic...

Idiopathic inflammatory myopathies (IIMs), or myositis, are a group of systemic autoimmune diseases leading to proximal muscle weakness. Myocarditis is a major cause of adverse outcomes. Yet, we know very little about the underlying immunologic processes that are driving myocarditis in the context of IIMs.

We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 12 individuals: myositis without myocarditis (n = 4), myositis with myocarditis (n = 4), and healthy controls (n = 4), to better understand the immunologic alterations characterizing this manifestation of the disease.

We found the most notable changes in B cells and natural killer (NK) cells of individuals with myositis with myocarditis compared to myocarditis alone. B cells showed 42 enriched pathways suggestive of increased DNA replication and repair, somatic hypermutation, and lymphocyte activation but a smaller proportion of memory B cells (β = -1.04, false discovery rate = 0.02), suggesting a greater activation of naive B cells in the periphery. NK cells, on the other hand, showed 223 enriched pathways suggestive of reduced proliferation but increased effector functions such as leukocyte degranulation, myeloid cell activation, and tumor necrosis factor secretion, suggesting that NK cells in patients with myositis with myocarditis are more activated but less proliferative than in myositis without myocarditis.

Together, these data suggest that B cells and NK cells may be playing important roles in mediating myocarditis pathogenesis in the context of IIMs.