In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.

Article Pre-analytical variability of the Lumipulse immunoassay for plasma biomarkers of Alzheimer’s disease was published on November 28, 2022 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 0, issue 0).

The complexity of neurodegenerative disorders necessitates an integrative approach that incorporates morphological, functional, and molecular biomarkers. The advent of highly sensitive single-molecule array (Simoa®) assays has significantly enhanced the accuracy of blood-based biomarker quantification, including glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181). This study evaluates the diagnostic utility of these biomarkers in neurodegenerative diseases. We analyzed data from 279 individuals from the PADUA-CESNE cohort: 120 with Parkinson's disease (PD), 88 with Alzheimer's disease (AD), 16 with frontotemporal dementia (FTD), 11 with multiple system atrophy (MSA), 14 with progressive supranuclear palsy (PSP), and 30 cognitively unimpaired controls. NfL levels were significantly lower in PD and AD compared to atypical parkinsonisms and FTD, effectively distinguishing MSA and PSP from controls. NfL also negatively correlated with Montreal Cognitive Assessment (MoCA) scores in AD and PD, indicating its association with cognitive decline. Elevated GFAP levels were observed in both PD and AD and inversely correlated with global cognition. Combining GFAP and p-tau181 improved AD differentiation from PD and other parkinsonian disorders, while the integration of all three biomarkers facilitated the distinction between AD and FTD. Notably, lower NfL levels (<20 ng/L) in conjunction with elevated p-tau181 were indicative of AD, whereas NfL levels below 40 ng/L were suggestive of PD. In conclusion, NfL serves as a sensitive indicator of neurodegeneration, albeit with limited specificity. However, by establishing biomarker concentration thresholds and integrating complementary biomarkers, blood-based assays may enhance the differential diagnosis of neurodegenerative diseases, providing valuable clinical insights.

Advances in analytical methods have recently paved the way to Alzheimer's disease (AD) biomarkers testing in blood along with the more established CSF testing. To ensure a forthcoming application of this low-invasive diagnostic that might allow to recognize early onset of dementia, appropriate pathological cut-points need to be defined. In this cross-sectional study we measured blood and CSF neurofilament light chain (NFL), phosphorylated tau (pTau 181), Amyloid-β1-42 (AB 1-42) and Amyloid-β1-40 (AB 1-40) on a fully automated chemiluminescent platform (Lumipulse, Fujirebio) in 80 cognitively impaired patients and 55 cognitively unimpaired subjects. Clinical cut points were calculated with receiver-operator characteristic (ROC) curve analysis and a head-to-head comparison of blood and CSF testing was performed. Blood NFL best discriminant thresholds to distinguish neurodegenerative diseases from controls varied age-dependently, being 19 and 33 pg/mL in subjects 50-65 years and > 65 years respectively. AD was best framed by AB 1-42/1-40 ratio < 0.079 and ptau181 > 1 pg/mL. Though a strong correlation for all biomarkers, only blood AB ratio was equal to CSF testing for AD diagnosis. The specific context of use might be considered to define the cut-offs of blood biomarkers of neurodegenerative diseases. Future efforts towards reference materials for each AD blood biomarker will improve clinical cut-offs.

Background and Purpose: The aim was to investigate whether neurofilament light chain (NfL) and profilin‐1 (PFN‐1) might qualify as surrogate disease and treatment‐response biomarkers by correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months.Methods: Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme‐linked immunosorbent assay (ELISA); PFN‐1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels. The concurrent effect of age and clinical phenotype was studied.Results: Neurofilament light chain levels were included in the reference ranges at baseline; a significant increase was measured during loading phase until 1 month. PFN‐1 was higher at baseline than in controls and then decreased during therapy until reaching control levels. Age had an effect on NfL but not on PFN‐1. NfL was partially correlated to functional scores at baseline and at last time point, whilst no correlation was found for PFN‐1.Conclusion: Cerebrospinal fluid NfL levels did not qualify as an optimal surrogate treatment biomarker in adult spinal muscular atrophy patients with a long disease duration, whilst PFN‐1 might to a greater extent represent lower motor neuron pathological processes. The observed biomarker level variation during the first 2 months of nusinersen treatment might suggest a limited effect on axonal remodeling or rearrangement.

The Apolipoprotein E (APOE) ε4 allele is a significant risk factor for Alzheimer's disease (AD). While genetic testing remains the gold standard for determining APOE status, protein-level quantification could offer advantages in clinical practice. This study evaluates a novel, fully automated immunoassay for quantifying APOE4 and total APOE (Pan-APOE) in plasma samples, assessing its accuracy and clinical utility compared to traditional genetic testing. Plasma samples from 65 patients (39 ε4 non-carriers, 21 ε4 heterozygous, 5 ε4 homozygous) were analyzed using the Lumipulse 1200 G APOE4 & Pan-APOE immunoassays. The APOE4/Pan-APOE ratio (Ratio%) was calculated to determine ε4 carrier status. Results were compared to genetic testing. Assay repeatability was evaluated using triplicate measurements from three patients with different genotypes. APOE4 and Pan-APOE protein levels and Ratio% differed significantly across ε4 status groups (p < 0.0001). The Ratio% showed no overlap between groups. ROC curve analysis for ε4 carrier identification showed an AUC of 1.00, with 100 % sensitivity and specificity at a 14 % cut-off. Perfect agreement was observed between the immunoassay and genetic testing (Cohen's kappa = 1.00, p < 0.0001). Intra-assay CV was <5 % for APOE4 and <8 % for Ratio%. This novel immunoassay demonstrates excellent and potential for faster results could offer advantages in clinical practice, particularly for AD therapy eligibility evaluation. However, further validation in larger, diverse cohorts is necessary before considering widespread clinical implementation.