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Ann Rheum Dis 72:445-452 doi:10.1136/annrheumdis-2012-201822
  • Basic and translational research
  • Extended report

Whole microvascular unit deletions in dermatomyositis

  1. Romain K Gherardi2–5
  1. 1Neuropediatry Unit, AP-HP, Necker - Enfants Malades Hospital, Paris, France
  2. 2AP-HP, Centre de Référence des Maladies Neuromusculaires “Garches-Necker-Mondor-Hendaye”, Paris, France
  3. 3INSERM U955-Team 10, Department of Neurosciences, “Mondor Biomedical Research Institute”, Paris est University, Créteil, France
  4. 4Departments of Histology and Pathology, AP-HP, Albert Chennevier-Henri Mondor Hospital, Créteil, France
  5. 5INSERM U841, Plateforme d'Imagerie Cellulaire et Tissulaire, Créteil, France
  1. Correspondence to Professor Romain K Gherardi, Departments of Histology and Pathology, Groupe Hospitalier Albert Chennevier – Henri Mondor, Créteil F-94010, France; romain.gherardi{at}hmn.aphp.fr
  • Received 5 April 2012
  • Accepted 19 July 2012
  • Published Online First 8 September 2012

Abstract

Objectives The pathophysiology of dermatomyositis (DM) remains unclear, combining immunopathological mechanisms with ischaemic changes regarded as a consequence of membranolytic attack complex (MAC)-induced capillary destruction. The study is a reappraisal of the microvascular involvement in light of the microvascular organisation in normal human muscle.

Methods Muscle microvasculature organisation was analysed using 3D reconstructions of serial sections immunostained for CD31, and histoenzymatic detection of endogenous alkaline phosphatase activity of microvessels. An unbiased point pattern analysis-based method was used to evaluate focal capillary loss. Double immunostainings identified cell types showing MAC deposits.

Results The normal arterial tree includes perimysial arcade arteries, transverse arteries penetrating perpendicularly into the endomysium and terminal arterioles feeding a microvascular unit (MVU) of six to eight capillaries contacting an average of five myofibres. Amyopathic DM cases (n=3) and non-necrotic fascicles of early DM cases (n=27), showed patchy capillary loss in the form of 6-by-6 capillary drop-out, corresponding to depletion of one or multiple MVUs. MAC deposits were also clustered (5–8 immunostained structures, including endothelial cells, but also pericytes, mesenchymal cells and myosatellite cells).

Conclusions Capillary loss may not be the primary cause of muscle ischaemia in DM. The primary event rather stands upstream, probably at the level of perimysial arcade arteries around which inflammatory infiltrates predominate and which lumen may show narrowing in chronic DM. Ischaemia-reperfusion injury, which is favoured by autoimmune backgrounds in experimental models and which activates the complement cascade in capillaries, could represent an hitherto unsuspected (and potentially preventable) mechanism of muscle damage in DM.