Résumé :
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DM is considered as an humorally-mediated disease specifically targeting endomysial capillaries , but its pathophysiology remains uncertain. Recently, plamacytoid dendritic cells have been found in perimysium providing novel insights into immunopathologic reactions at work in DM (Greenberg et al, Neurology 2007; 69:2008-19). We made a reappraisal of DM-associated microvascular changes. Evidence of C5b-9 deposits (MAC) in muscle capillaries leading to capillary loss is a central finding in DM. It was initially regarded as the result of specific antigen-antibody recognition but, to date, no endothelial cell autoantigen has been identified in DM. Alternatively, MAC microvascular deposits may result from an ischaemia-reperfusion (I/R) injury, a situation characterized by 'no reflow phenomenon' which describes persistently reduced tissue perfusion after temporary artery occlusion, which is associated with local reactive oxygen species release, natural IgM and complement activation, capillary damage, and interstitial oedema formation (Weiser et al, J Exp Med 1996; 183: 2343-8). To substantiate the view that I/R, resulting from upstream arteriolar inflammatory changes, may account for MAC deposits and subsequent capillary depletion in DM, we first determined the number of capillaries fed by a single terminal arteriole (microvascular unit: MVU) in normal adult deltoid muscle. 3D reconstructions of 500 serial crossections immunostained for CD31 showed that terminal arterioles, roughly perpendicular to myofibers, fed multiples of 10, longitudinally oriented, capillaries. Then we analysed deltoid muscle biopsies of DM patients to assess spatial distribution of both MAC deposits (acute DM) and capillary loss, using multiple immunostainings, large tissue reconstructions and point-pattern analysis. Microvascular MAC deposition was either endothelial or abluminal (pericytic as suggested by???SMA immunostaining), and occasionally involved adjacent CD56+ satellite cells. Both MAC deposition and vascular depletion occured in MVU-sized clusters of neighboring capillaries. We propose that I/R injury affecting individual MVU territories account for focal microvascular MAC deposition and depletion observed in DM.
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