The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis

Abstract

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM—HR: 1.05, CI: 1.01–1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.

Carbohydrate ligand engagement with CD11b enhances differentiation of tumor-associated myeloid cells for immunotherapy of solid cancers

“…According to literature, healthy individuals typically have only 1–5% of activated CD11b in the ‘open’ conformation in their peripheral blood, whereas patients with tumor burdens may have 10–30%. 35 Based on this information, we believe that our findings are supported, demonstrating that BG34-200 can directly, effectively, and specifically target tumor-associated CD11b + inflammatory monocytes by engaging with the activated CD11b in the open conformation I domain.…”

Blood biomarkers in ALS : challenges, applications and novel frontiers

“…However, confirmation by larger multi‐centre studies for most putative biomarkers is lacking 82 . A recent study reported a steep increase of monocyte cells expressing the inflammation suppressing active CD11b integrin in blood from patients with ALS, with a slow disease progression 99 . The observation of a peripheral rise of myeloid cells is in line with the reported longitudinal increase of neurotrophin receptor p75 extracellular domain (p75ECD) in urine, from patients with ALS compared to healthy controls.…”

Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis (RAP-ALS study)

“…Together with the above mentioned limitation, the increase in classical monocytes and the reduction in intermediate monocytes in patients treated with rapamycin, is even more difficult to interpret because of the uncertainty on their role in ALS, and if monocyte subsets and activation profiles are altered depending on the stage of the disease (i.e. the changes are a response to disease and their changes suggest that the immune system becomes more activated as the disease progresses) or if they are instead pathogenetic deserves further studies [25][26][27] .…”