ClinicoPathological Correlation (CPC) ImmunoTechnologies for Monitoring Lymphotoxin Alpha

• Published in: The Journal of immunology (1950) 2020-05, Vol.204 (1_Supplement), p.86-86.58
• Main Authors: Harbi, Shaghayegh, Wang, Rong, Harbi, Vahid Dean, Kerbawy, John, Park, Hannah Lui, Gonzales, John
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.86.58

Neuroinflammation has been proposed as a target for neuroprotection. Therefore significant opportunities for preventing neurologic decline exist. ClinicoPathological Correlation (CPC) ImmunoTechnologies are critically needed for clinical utility for acute and chronic immunological and inflammatory disorders (including autoimmune neurological disorders such as Parkinson’s disease and Alzheimer’s disease) to determine if an individual has variants associated with a higher risk of disease (Gain of Function [GoF] variants); and elevated levels of analytes (circulating biomarkers). We hypothesize the neurovascular compartment plays a critical role in neurodegeneration. Using a multipronged approach, we identified specific immune cell subsets and inflammatory factors in the blood, which can potentially play a critical role in the early stages of neurodegeneration by disrupting homeostatic regulation, destabilizing the neurovascular compartment; and elevated levels of analytes (proteomic multiplexed quantification) in the cerebrospinal fluid (CSF) and plasma, which can potentially serve as robust, indicative biomarkers consistent with model of neuroinflammation contributing to neurovascular dysfunction, potentially leading to neurodegeneration. More specifically, we identified analytes (lymphotoxin/TNF-beta/LTA) in the plasma (low levels in CSF); TNF-alpha levels were low in plasma and CSF. Next-generation sequencing enabled the identification of risk variants, pathogen/virus profiles and LTA GoF variant strongly associated with increased protein production. We included distinct LTA inflammatory/autoimmune disease controls (rheumatoid arthritis, multiple sclerosis, uveitis or vasculitis).