Biomarkers in Inflammatory Myopathies-An Expanded Definition

Abstract

Biomarkers as parameters of pathophysiological conditions can be of outmost relevance for inflammatory myopathies. They are particularly warranted to inform about diagnostic, prognostic, and therapeutic questions. As biomarkers become more and more relevant in daily routine, this review focusses on relevant aspects particularly addressing myopathological features. However, the level of evidence to use them in daily routine at presence is low, still since none of them has been validated in large cohorts of patients and rarely in independent biopsy series. Hence, they should be read as mere expert opinions. The evaluation of biomarkers as well as key biological parameters is an ongoing process, and we start learning about relevance of them, as we must recognize that pathophysiology of myositis is biologically incompletely understood. As such this approach should be considered an essay toward expansion of the definition "biomarker" to myositis, an emerging field of interest in biomedical research.

Keywords: DM; IBM; IIM; IMNM; biomarker; morphology; myositis; myositis-specific-autoantibodies.

Figure 1

Characteristic example of anti-SRP+ IMNM. (A) Diffuse myofiber necrosis in different stages of single cell necrosis and regeneration (H&E stain, original magnification x200). (B) MHC class I sarcolemmal stain with diffuse character (original magnification x200). (C) CD68+ macrophages confined to myophagocytosis and diffusely distributed in the endomysium (original magnification x200). (D) C5b-9 complement deposition on the sarcolemma of myofibers (original magnification x400).

Figure 2

Characteristic example of anti-Mi2+ DM. (A) Perifascicular atrophy of myofibers (PFA) (H&E stain, original magnification x100). Electron microscopy: endothelial tubuloreticular inclusions in endothelial cells (original magnification x30.000). (B) Perifascicular MHC class I staining with a decreasing gradient toward the centrofascicular region (original magnification x200). (C) Perimysial macrophage infiltrate with extension to the endomysium (CD68, original magnification x200). (D) C5b-9 complement on the sarcolemma of myofibers (original magnification x200).

Figure 3

Characteristic anti-Jo1-positive ASS-associated myositis. (A) Necrotic myofibers confined to the perifascicular region (H&E stain, original magnification x200). Electron microscopy: intranuclear actin inclusions in myonuclei (insert; original magnification x20.000). (B) Sarcolemmal MHC class I stain is diffusely positive (original magnification x200) and MHC class II confined to the sarcolemma and sarcoplams of the perimysial myofibers (insert; original magnification x200). (C) Lympho-monocytic infiltrate extends into the endomysium (CD68+ macrophages and lymphocytes (original magnification x200). (D) Sarcolemmal C5b-9 and necrotic myofibers predominant in the perifascicular region (original magnification x200).

Figure 4

Characteristic morphology of sIBM. (A) Diffusely distributed necrotic myofibers in a severely myopathic tissue (original magnification x100). (B) Strong sarcolemmal and sarcoplasmic MHC class I staining (MHC class II fokal stain but no perifascicular pattern) [original magnification x100 (not shown)]. (C) Dense endomysial lymphocytic infiltrate (original magnification x200). (D) Presence of e.g., p62+ vacuoles in the sarcoplasm (original magnification x200). (E) Mitochondrial pathology with many COX-negative and SDH-positive fibers (original magnification x400) and paracristalline inclusions on EM (original magnification x20.000). (F) Electron microscopy: tubulofilaments (original magnification x30.000).

Figure 5

Characteristic example of anti-TIF1γ+ DM. Perifascicular pathology of myofibers (PFP) with: (A) atrophic fibers, punched-out vacuoles and violaceous fibers on Gömöri trichrome (original magnification x100). (B) abundant ghost fibers at the edge of fascicles (original magnification x100). (C) predominant complement (C5b-9) deposits on capillaries (original magnification x100). (D) MHC class I staining with perifascicular to centrofascicular gradient (original magnification x100). (E) MxA stain highlighting interferon signature-related pathology predominantly in the perifascicular region (original magnification x100). (F) Presence of COX paleness in the perifascicular region (original magnification x100).