Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process.
In this work we show that patients with sporadic amyotrophic lateral sclerosis exhibit immunological alterations in their blood, with respect to healthy controls, such as: i) increased levels of CD4+ cells and decreased levels of CD8+ T lymphocytes, the latter due to the reduced expression of the anti-apoptotic molecule Bcl-2; ii) significantly reduced CD4+CD25+ regulatory T (Treg) cells and monocytes (CD14+) levels in patients at a less severe stage of disease, suggesting their early recruitment towards the CNS area of primary neurodegeneration; iii) reduced expression of HLA-DR and CCR2 expression, as markers of activation, in monocytes. Since resident microglia partially derives from circulating activated monocytes and Treg cells are known to interact with the local microglia, this study strengthens the hypothesis of an involvement of the adaptive immune system associated with a neuroinflammatory process in the pathobiology of ALS.
Mantovani
Stefania
S
Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy.
Garbelli
Silvia
S
Pasini
Alessandra
A
Alimonti
Dario
D
Perotti
Cesare
C
Melazzini
Mario
M
Bendotti
Caterina
C
Mora
Gabriele
G
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009187:Myelitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D054390:Receptors, CCR2 / Q000032:analysis / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
D000954:Antigens, Surface; C515334:CCR2 protein, human; D006684:HLA-DR Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D054390:Receptors, CCR2