Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis

Abstract

ObjectiveTo study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM).MethodsEvaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR.ResultsWe defined 3 aDM subgroups—classic (containing occasional B cells without clusters), B-cell–rich, and follicle-like aDM—further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature.ConclusionThese data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon–related immunity.

NanoString technology distinguishes anti‐TIF‐1γ+ from anti‐Mi‐2+ dermatomyositis patients

“…Both anti-TIF-1γ + and anti-Mi-2 + patients' skeletal muscle biopsies revealed strong dysregulation of immune response-related genes compared to NDCs. In line with previous reports, these included well-known type 1 IFN-inducible genes such as ISG15, ISG20, SIGLEC1, IRF7, and MX1 (45)(46)(47)(48)(49)(50). We also identified subgroupspecific differences: TIF-1γ + patients showed upregulation of HLA-G, HLA-DQA1, and BAGE, the latter being a well-known tumor antigen (51)(52)(53) present in many cancers (54).…”

Using peripheral blood immune signatures to stratify patients with adult and juvenile inflammatory myopathies

“…Conversely, B cells have not been thought to be as vital as T cells in the pathogenesis of IIM although they do play an important role. Not only are B cells found in the infiltrates of muscle tissue in DM patients, there is a high detection of myositis-associated (MSA) and specific (MSS) autoantibodies (12)(13)(14). The expression of B cell activating factor (BAFF) has been associated with anti-Jo-1 antibodies in DM muscle tissue, specifically in the perifascicular area (15).…”

The Role of Immune Cells in the Pathogenesis of Idiopathic Inflammatory Myopathies

“…Despite not being as common as T cells, muscle-infiltrating B cells in muscle biopsy samples from patients with IIMs are clonally diversified and display deviant immunoglobulin V H gene repertoires, indicating chronic local antigen-driven humoral responses [ 98 , 99 ]. Interestingly, the quantity of B cells and the formation of ectopic follicle-like structures in the muscles of DM patients have been associated with the level of cytokines or chemokines involved in lymphoid neogenesis as well as type I interferon-related immunity [ 100 ]. However, concentrated collections of germinal-centre-like B cell follicles are absent in the muscles of patients with myositis.…”