Bench to bedside review of myositis autoantibodies

Abstract

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics.

Keywords: Anti-nuclear antibodies; Autoantibodies; Dermatomyositis; HMGCR; Immune-mediated necrotizing myopathy; Immunofluorescence; Inclusion body myositis; MDA5; Myositis; Polymyositis.

Fig. 1

IIF on HEp-2 ANA slides of myositis-specific autoantibodies from patients with IIMs (EUROIMMUN, Lübeck, Germany). a Anti-Jo-1 and b anti-Jo-1 and anti-Ro52, c anti-PL-7, d anti-PL-12, e anti-KS, f anti-Mi-2, g anti-SAE-1, h anti-MDA5, i anti-NXP-2 and j anti-NXP-2 with coiled bodies, k anti-TIF1γ, l anti-SRP

Fig. 2

Immunofluorescence patterns from patients with IMNMs with anti-SRP and anti-HMGCR antibodies on HEp-2 ANA slides (EUROIMMUN, Lübeck, Germany) and rat liver and stomach slides (DiaSorin, Italy), compared to AMA-M2 antibodies. a Anti-SRP cytoplasmic dense fine speckled pattern on HEp-2, b chief cells on stomach and c fine granular liver staining; d AMA-M2 cytoplasmic reticular on HEp-2, e granular staining of parietal stomach cells and f diffused fluorescence of hepatocytes; g Anti-HMGCR faint cytoplasmic fluorescence on few numbers of HEp-2 cells, h negative stomach and i fine cytoplasmic fluorescence of scattered hepatocytes around the biliary ducts

Fig. 3

Myositis-associated autoantibodies and some peculiar IIF pattern on HEp-2 ANA slides (EUROIMMUN, Lübeck, Germany). a anti-PM-Scl-100, b anti-PM-Scl-75, c anti-U1-snRNP, d anti-Ku, e anti-fibrillarin, f cytoplasmic discrete dots as seen in anti-Su/Ago2, g nuclear few nuclear dots as seen in anti-SMN, h punctate nuclear envelope as seen in anti-NUP