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Neuroinflammation is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), but only limited data are available on systematic peripheral and central immune cell profiles in ALS. We studied detailed immune profiles of 73 ALS patients and 48 healthy controls (controls) in peripheral blood by fluorescence-activated cell sorting as well as cytokine expression profiles in serum. In a subgroup of 16 ALS patients and 10 controls we additionally studied cerebrospinal fluid (CSF) samples. In peripheral blood, T cell subtypes presented a shift towards pro-inflammatory Th 1 and Th 17 cells whereas anti-inflammatory Th2 and T regulatory cells were decreased. Important players in innate immunity including distinct monocyte (Mo) and natural killer (NK) cell subtypes were changed in ALS patients compared to controls. Pro-inflammatory serum cytokines such as interleukin (IL)-1 beta, IL-6 and interferon-gamma (IFN-gamma) were increased and the anti-inflammatory cytokine IL-10 was decreased. Correlation analysis revealed moderate negative correlations between Th1 and Th17 to the ALS functional rating scale revised (ALSFRS-R) and to forced vital capacity. In CSF samples, no relevant alteration of the immune profile was found. In conclusion, the immune profile in ALS was shifted towards a Th1/Th17 cell-mediated pro-inflammatory immune response and correlated to disease severity and progression. Large prospective studies are needed to confirm these findings.

Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis