Severe muscle damage with myofiber necrosis and macrophage infiltrates characterize anti-Mi2 positive dermatomyositis.

Marco Fornaro, Francesco Girolamo, Lorenzo Cavagna, Franco Franceschini, Margherita Giannini, Angela Amati, Anna Lia, Marilina Tampoia, Dario D'Abbicco, Lorenzo Maggi, Micaela Fredi, Giovanni Zanframundo, Liala Moschetti, Laura Coladonato, Florenzo Iannone

Journal: Rheumatology (Oxford, England) 2021;60(6):2916-2926

PMID: 33249503

Full Text on Ovid Technologies, Inc. View on PubMed

Abstract

OBJECTIVE

The aim of our study was to investigate clinical and histopathological findings in adult DM patients positive for anti-Mi2 (anti-Mi2+) antibodies compared with DM patients negative for anti-Mi2 (anti-Mi2-).

METHODS

Clinical data of adult DM patients, who fulfilled EULAR/ACR 2017 classification criteria, were gathered from electronic medical records of three tertiary Rheumatology Units. Histopathological study was carried out on 12 anti-Mi2+ and 14 anti-Mi2- muscle biopsies performed for diagnostic purpose. Nine biopsies from immune mediated necrotizing myopathy (IMNM) patients were used as control group.

RESULTS

Twenty-two anti-Mi2+ DM [90.9% female, mean age 56.5 (15.7) years] were compared with 69 anti-Mi2- DM patients [71% female, mean age 52.4 (17) years]. Anti-Mi2+ patients presented higher levels of serum muscle enzymes than anti-Mi2- patients [median (IQR) creatine-kinase fold increment: 16 (7-37)vs 3.5 (1-9.9), P <0.001] before treatment initiation. Moreover, a trend towards less pulmonary involvement was detected in anti-Mi2+ DM (9.1% vs 30.4%, P =0.05), without any case of rapidly progressive interstitial lung disease. At muscle histology, anti-Mi2+ patients showed more necrotic/degenerative fibres than anti-Mi2- patients [mean 5.3% (5) vs 0.8% (1), P <0.01], but similar to IMNM [5.9% (6), P >0.05]. In addition, the endomysial macrophage score was similar between anti-Mi2+ and IMNM patients [mean 1.2 (0.9) vs 1.3 (0.5), P >0.05], whereas lower macrophage infiltration was found in anti-Mi2- DM [mean 0.4 (0.5), <0.01].

CONCLUSIONS

Anti-Mi2+ patients represent a specific DM subset with high muscle damage. Histological hallmarks were a higher prevalence of myofiber necrosis, endomysial involvement and macrophage infiltrates at muscle biopsy.

Address: Unit of Rheumatology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.; Unit of Human Anatomy and Histology, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy.; Rheumatology Division, University and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.; Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili and University of Brescia, Brescia, Italy.; Unit of Rheumatology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.; Service de Physiologie, Unité d'Explorations Fonctionnelles Musculaires, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.; Unit of Neurophysiopathology, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.; Clinical Pathology Unit, Department of Biomedical Sciences and Human Oncology, University 'Aldo Moro' of Bari, Bari, Italy.; Institute of General Surgery 'G Marinaccio', Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

DOI: 10.1093/rheumatology/keaa739

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Adult, Aged, Autoantibodies, Cohort Studies, Dermatomyositis, Female, Humans, Macrophages, Male, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Middle Aged, Necrosis, Retrospective Studies