Abstract 2066: Ectopic Lymphoid Microstructures are Central to the Pathogenesis of Juvenile Dermatomyositis
Authors
Consuelo M. López de Padilla1, Abbe N. Vallejo2, Ann M. Reed1.
Background:
Inflammatory infiltrates in juvenile dermatomyositis (JDM) muscles consist mainly of activated lymphocytes and macrophages. Recently, Dr. Reed and colleagues demonstrated that activated plasmacytoid dendritic cells (pDC) are also major components of the muscle inflammation in new-onset JDM. These cells tend to be organized as aggregates, and produce CCL19 and CCL21 locally. These observations suggest that inflamed JDM muscle have all of the elements needed to drive ectopic formation of lymphoid tissue which would be a potential focus of pDC maturation.
Methods
The histological features of inflammatory infiltrates in JDM were examined further, and whether they acquired lymphoid tissue architecture was evaluated. Non-inflamed muscle and tonsils were used as controls.
Results
Results showed three patterns of organization of cellular infiltrates in JDM muscles; namely, (a) dense inflammatory infiltrates resembling lymphoid follicles (22.3% of cases), (b) dense infiltrates lacking of specific lymphoid microstructures (55.5%), and (c) inflammatory cells distributed diffusively without evidence of lymphoid organization (22.2%). None of the control muscles displayed these patterns. Muscle sections from JDM and non-myositis controls were also stained for an endothelial cell differentiation antigen known to be selectively expressed on HEVs. This antigen was not detectable in the vascular endothelium of muscle controls.
Conclusion
Collectively, these results demonstrate formation of ectopic lymphoid tissues in the inflamed muscle tissue in new-onset JDM. T-/B-cell aggregates surrounding activated pDCs indicate foci of inflammation, and the abundance of CD45RA+ T cells indicates that they are primary sites of T cell activation. FDC-HEV networks, along with expression of the homeostatic chemokines CCL19 and CCL21 indicate active neolymphogenesis. Thus one can postulate that formation of ectopic lymphoid follicles profoundly influences the clinical outcomes of JDM. Such lymphoid microstructures could be key targets for therapy.
Editorial Comment
Formation of ectopic lymphoid follicles appears to greatly influence the clinical outcomes of JDM. These lymphoid microstructures could be novel targets for therapy.
