B-cell infiltration in inclusion body myositis: association with inflammasome-related signaling and enhanced myotoxicity

This is the authors' abstract. We don't add key points for this paper.

Inclusion body myositis (IBM) is a degenerative, intractable, inflammatory myopathy with an immune pathomechanism. CD8+ T cell-mediated myocytotoxicity is considered a pivotal inflammatory pathogenic mechanism in IBM; however, there have been limited pathological investigations into the detailed immune mechanisms and the role of B cells in IBM. In this study, we examined 48 consecutive muscle biopsies from patients fulfilling the diagnostic criteria for IBM and assessed the extent of CD20+ B-cell infiltration. 41 cases (85.4%) showed no-to-mild B-cell infiltration (designated as IBM-B-cell), whereas 7 (14.6%) showed moderate infiltration (IBM + B-cell); among these, 5 had B-cell foci resembling lymphoid follicles. There was no significant difference in clinical profiles between cases of IBM-B-cell and IBM + B-cell except for serum IgG titer. All 7 cases of IBM + B-cell were uncomplicated by other autoimmune diseases and were considered pure IBM. Histopathologically, the inflammatory infiltrate area and C5b-9 sarcolemmal deposits on myofibers were significantly increased in muscle tissues of IBM + B-cell. RNA sequencing of muscle specimens and subsequent enrichment analyses revealed that the NOD-like receptor (NLR) signaling pathway and the positive regulation of interleukin-1 beta (IL-1β) production are upregulated uniquely in IBM + B-cell. In this group, the CD8+ T-cell infiltrated area (%) was significantly higher than IBM-B-cell. The intra-myofiber NLR family pyrin domain-containing 3 (NLRP3)-positive aggregates and IL-1β deposition on infiltrated cells, perimysium, and a fraction of myofiber cytoplasm were present and tended to be prominent in IBM + B-cell. Our results demonstrated that B-cell infiltration can be present in more than 10% of pure IBM series, which may reflect a subgroup with upregulated inflammasome pathways. An activated inflammasome may be involved in the pathomechanism of IBM and serve as the core stimulator of both cytotoxic and humoral responses.