Extranodal Lymphoid Microstructures in Inflamed Muscle and Disease Severity of New-Onset Juvenile Dermatomyositis

Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 04/2009; 60(4):1160-72. DOI: 10.1002/art.24411
Source: PubMed


Juvenile dermatomyositis (DM) is an autoimmune disease of childhood characterized by lesions in skin and muscle that are populated by plasmacytoid dendritic cells (PDCs) and lymphocyte infiltrates. We undertook this study to examine the cellular composition, organization, and molecular milieu of the cellular infiltrates in muscle in juvenile DM and to correlate the infiltrates with clinical disease manifestations.
Since PDCs and lymphocyte foci express CCL19 and CCL21, we investigated for in situ formation of lymphoid microstructures that could be sites of extranodal immune activation.
Analyses of muscle biopsy samples from children with new-onset juvenile DM showed 3 categories of lesions: diffuse infiltrates, lymphocytic aggregates lacking follicle-like organization, and follicle-like structures. The last of these exhibited elements of classic lymphoid follicles, including networks of follicular dendritic cells and high endothelial venules. They also expressed high levels of CXCL13 and lymphotoxins known to support lymphoid organogenesis. There were also resident naive CD45RA+ T cells and maternally derived B cells and PDCs. Patients with diffuse infiltrates or lymphocytic aggregates were responsive to standard therapy with steroids and methotrexate, but those with follicle-like structures tended to have severe disease that required additional agents such as intravenous Ig or rituximab.
These data suggest that lymphoneogenesis is a component of the early disease process in juvenile DM. Ectopic lymphoid structures could indicate a severe course of disease; their early detection could be a tool for disease management.

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Available from: Consuelo Lopez De Padilla, Jul 16, 2014
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    • "In a major knowledge gap, the contribution of TLT to pathology is defined predominately by correlation and association. The presence of TLT in man is associated with more severe disease, e.g., in juvenile dermatomyositis, Sjogren’s syndrome, and multiple sclerosis (163–165). In rodents, TLT can enhance viral defense in lung infections, naïve T cell recruitment, and epitope spreading in diabetes and exacerbate heart allograft rejection (152, 166–168). "
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    • "Also, muscle fibers positive for this chemokine and infiltrating lymphocytes positive for the receptor have been demonstrated [17]. Further dissection for extranodal lymphoid microstructures has been performed, and indeed such structures can be found [18]. The existence of such lymph node structures indicates that lymphocyte activation and differentiation could take place within the muscle, and there is support from studies of B cells, plasma cells, and immunoglobulin sequences that plasma cell differentiation can take place in this location [19]. "
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