title: Whole microvascular unit deletions in dermatomyositis.
abstract: OBJECTIVE
  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.
authors.affiliation: Neuropediatry Unit, AP-HP, Necker - Enfants Malades, Hospital, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gitiaux
authors.forename: Enis
authors.initials: E
authors.lastname: Kostallari
authors.forename: Peggy
authors.initials: P
authors.lastname: Lafuste
authors.forename: Francois-Jerome
authors.initials: FJ
authors.lastname: Authier
authors.forename: Christo
authors.initials: C
authors.lastname: Christov
authors.forename: Romain K
authors.initials: RK
authors.lastname: Gherardi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003882:Dermatomyositis / Q000473:pathology*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D055815:Young Adult