# Neurosarcoidosis: Clinical Phenotype, Biomarkers and Immunopathogensis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $676,226

## Abstract

Neurosarcoidosis (NS) represents the neurologic manifestations of sarcoidosis, a multisystemic granulomatous
inflammatory disorder of unknown cause. NS may be observed in 5-15% of patients with sarcoidosis, a
worldwide disease that disproportionally impacts African Americans and whites of northern European heritage.
Our preliminary studies showed NS has a wide spectrum of clinical phenotypes that includes meningitis,
encephalitis, and myelitis. We also found that cerebrospinal fluid (CSF) from patients with NS reveal a unique
profile of immune mediators frequently associated with infections (interferon-γ, tumor necrosis factor-α and
interleukin-6) and antibody signatures linked to Mycobacteria antigens. Based upon these observations, we
hypothesize that the pathogenesis of NS is due to a neuro-inflammatory response to antigens derived from
exposure to infective agents in susceptible individuals with the clinical phenotype determined by specific gene
expression signatures. This study engages two centers with existing cohorts of NS patients with prospective
collection of clinical data and biological samples to dissect CSF immunopathogenic pathways, define immune
profiles, and uncover antigens or pathogens which may be associated with NS phenotypes. Our specific aims
focus on associating clinical NS phenotypes with immune profiles and gene expression pathway signatures in
CSF and the link with host or pathogen-associated antibodies. In Aim 1, we will perform rigorous phenotyping
of NS patients, and use biological samples such as CSF to characterize previously identified cytokine and
acute phase reactants and their usefulness as biomarkers of disease outcome. In Aim 2, we will use host
CSF transcriptional profiling to identify specific molecular signatures and pathways present in NS will establish
immunopathogenic mechanisms and factors that contribute to dynamic neuroinflammation and disease
progression. In Aim 3, we will use state of the art phase display libraries and phage-displayed
immunoprecipitation sequencing techniques to determine the presence of antibodies to host and microbial-
associated antigens which may identify triggering mechanisms related to the NS inflammatory process. All
aims are well integrated as Aim 1 will provide a well characterized and phenotyped cohort of patients with NS
which would facilitate a more precise identification of disease pathways in the CSF transcriptomic analysis
outlined in aim 2, and host- or pathogen-related antibody response discovery in Aim 3. The studies proposed
will address critical voids in our understanding of the pathogenesis of NS and suggest future novel therapeutic
strategies.

## Key facts

- **NIH application ID:** 10445211
- **Project number:** 1R01NS123712-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CARLOS A PARDO-VILLAMIZAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $676,226
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445211

## Citation

> US National Institutes of Health, RePORTER application 10445211, Neurosarcoidosis: Clinical Phenotype, Biomarkers and Immunopathogensis (1R01NS123712-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445211. Licensed CC0.

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