Neuropathogenesis of Errors of Immunity

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

To characterize the neurological course of patients with errors of immunity, we formulated a clinical protocol to assess the neurological manifestations of both known and unknown errors of immunity. This IRB-approved protocol provides us with a clinical platform to evaluate patients at the NIH Clinical Center from a clinical and neurological standpoint. Additionally, we collect a variety of bio-samples such as serum, cerebrospinal fluid (CSF), PBMCs, and more, to be utilized for research-based assays. We have developed a comprehensive immunophenotyping panel utilizing the 42-color Cytek Aurora system, and we have perfected a method that enables us to immunophenotype CSF cells immediately after collection. Furthermore, we have established a protocol for performing single-cell RNA-sequencing (scRNA-Seq) or CITE-seq on the same cells. These techniques afford us a platform for more in-depth investigation into the phenotype and function of immune cells in CSF. We have also collected a sufficient number of samples from healthy control donors to serve as controls as we continue to recruit new patients. In order to address the underlying mechanisms of Immune Dysregulation in neurons and glial cells, we have established a platform using iPSCs derived from patient lines or CRISPR-Cas9 engineered lines from healthy donors with specific gene defects. These cells are then differentiated into neurons and brain organoids. Electrophysiological techniques have been employed to evaluate and compare neuronal functions. Additionally, we use a variety of molecular biology and omics methods to investigate the role of gene mutations in the nervous system.