Predictors from systemic and neuro-inflammation in amyotrophic lateral sclerosis: A monocentric experience

While the role of systemic and neuroinflammatory players is actually consolidated in amyotrophic lateral sclerosis (ALS) pathogenesis, a representative and reliable panel of inflammatory prognostic biomarkers is still lacking. This retrospective study on 182 ALS patients from the Modena ALS Center, investigates biomarkers of axonal injury (neurofilaments) and microglial and astrocytic activation (SerpinA1, TREM2, CHI3L1, OPN and S100B, respectively). In a subpopulation of patients, we examined blood count-derived parameters, including the Systemic-Immune-Inflammation index (SII), Systemic Inflammation Response Index (SIRI) and Aggregate Systemic Inflammation Index (AISI). All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups. SerpinA1_CSF was significantly lower in females [4.43 μg/ml (IQR 2.76-6.3) vs 5.61 μg/ml (IQR 3.39-9.16),p = 0.032], while SII indexes was oppositely distributed [higher in females, 540.67 (IQR 363.05-807.24) vs 384.89 (IQR 307.5-578.52),p = 0.015]. In univariate survival analysis, without overcoming neurofilaments, SIRI (HR 1.43, 95 %CI 1.03-1.966,p = 0.03), AISI (HR 1.002, 95 %CI 1.001-1.003, p = 0.002) and SII (HR 1.001, 95 %CI 1.0003-1.001,p = 0.003) impact negatively on survival, with AISI retaining its power at multivariate analysis (HR 1.002, 95 %CI 1.0004-1.001,p = 0.012). SerpinA1_CSF levels influenced survival only for females (HR 1.042, 95 %CI 1.0065-1.078,p = 0.02), in a similar manner of SIRI (HR 1.483, 95 %CI 1.082-2.0334,p = 0.014) and SII (HR 1.00099, 95 %CI 1.0008-1.003,p = 0.001). Our data revealed the influence of sex on survival by SerpinA1_CSF, CHI3L1_CSF and systemic biomarkers in females. However, both neurofilaments and CHI3L1_CSF outperform the other neuroinflammatory biomarkers at predicting rate of disease progression, so the prognostic meaning of these measure alone remains unconclusive, requiring larger collaborative studies.