The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy

Abstract

Introduction: To characterize cellular infiltrates in muscle biopsies from patients with anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMGCR)-associated myopathy.

Methods: Biopsies from 18 anti-HMGCR myopathy and 7 control dermatomyositis patients were analyzed.

Results: CD4+ and CD8+ T-cells were scattered within the endomysium in 50% of anti-HMGCR biopsies. All anti-HMGCR biopsies included increased endomysial and/or perivascular CD163+ M2 macrophages; CD11c+ M1 macrophages were present in 18.8%. CD123+ plasmacytoid dendritic (PD) cells were observed within the endomysium and perivascular spaces in 62.5% of anti-HMGCR biopsies. Membrane attack complex was deposited on endothelial cells in 50% and on the sarcolemma of nonnecrotic muscle fibers in 85.7% of anti-HMGCR cases. Major histocompatibility complex class I antigen was up-regulated in 87.5% of the anti-HMGCR cases.

Conclusions: In addition to necrosis, scattered CD4+, CD8+, and PD cells are characteristic of anti-HMGCR myopathy. Predominant M2 polarization suggests infiltrating macrophages are more likely to be involved with tissue repair than destruction.

Keywords: anti-HMGCR myopathy; autoimmune myopathy; immune-mediated necrotizing myopathy; muscle histology; myositis.

Figure 1

Representative serial muscle biopsies sections from anti-HMGCR myopathy (A, C, E, G, I, K) and DM (B, D, F, H, J, L) patients were stained with H&E (A, B), anti-CD3 (C, D), CD4 (E, F), CD8 (G, H), CD20 (I, J), and CD68 (K, L). In the anti-HMGCR case, H&E staining reveals degeneration, necrosis, and myophagocytosis of endomysial myofibers. IHC staining shows sparse endomysial CD3, CD4, and CD8 cells with no CD20 positive cells. In anti-HMGCR myopathy, most inflammatory infiltrates are CD68-positive macrophages. In the DM case, H&E staining shows myofiber atrophy, myofiber degeneration, and inflammatory infiltrates. Inflammatory infiltrates from the DM case include numerous CD68 positive macrophages with similar numbers of CD3, CD4, and CD8 cells and a few scattered CD20 cells.

Figure 2

Representative serial sections from 2 typical anti-HMGCR myopathy patients (A,B and C,D) show significant staining for M2 macrophages with anti-CD163 (A,C) but no M1 macrophages staining positive for CD11c (B,D). In contrast, sections from a single patient who was later diagnosed with cholangiocarcinoma had a modestly increased number of CD11c positive M1 macrophages (F,H) in addition to large numbers of M2 macrophages which stain positively for CD163 (E,G).

Figure 3

Immunostaining reveals a modest number of CD123 positive plasmacytoid dendritic cell cells (arrowheads) within the endomysium of 2 different anti-HMGCR myopathy patients (A and B). Note that both inflammatory cells (arrowheads) and myonuclei are stained with anti-CD123.