Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights Into Inflammatory Neuropathies

Abstract

Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies. Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63). Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies. Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies.

NK cell markers predict the efficacy of IV immunoglobulins in CIDP

“… 30 Furthermore, a recent study on the CSF of patients with inflammatory neuropathies revealed a distinctive increase in NK cell numbers—indicating an underestimated role of NK cells in inflammatory neuropathies. 31 …”

Deciphering immune mechanisms in chronic inflammatory demyelinating polyneuropathies

“…Moreover, peripheral blood CD8 + T cells from patients with CIDP have extensive oligoclonal expansion compared with CD4 + T cells. More recently, we found that CSF composition of patients with CIDP is disease specific, with a significant increase in cytotoxic cell types NKT cells and CD8 + T cells (45,46). In mouse CIDP models, the role of CD8 + T cells requires further clarification.…”

“…Histology (33,45,69) and electron microscopy (70, 71) on nerve biopsies from patients with CIDP has provided important information about CIDP pathogenesis. A deeper understanding of molecular mechanisms was gained by FACS analysis of patient blood (72) and CSF (46,72). Notably, transcriptomic technologies are beginning to reveal a much higher resolution view of the cellular composition of the PNS in homeostasis and CIDP disease development.…”

Cytotoxic Immunity in Peripheral Nerve Injury and Pain

“…For example, missense loss-of-function mutations in perforin have been identified in some CIDP patients (Buttini et al, 2015), and a study of 22 CIDP patients and 22 healthy controls showed the proportion of CD3 − CD56 + NK cells was lower in the blood of patients (Sanvito et al, 2009). CSF from inflammatory neuropathy patients contains elevated NK cells in association with GBS, whereas CD8 + T and CD3 + NKT cells levels were increased in CIDP patients (Heming et al, 2019). These findings suggest that heterogeneity in the cytotoxic cellular immune response could play role in differentiating the acute and chronic forms of inflammatory peripheral neuropathy.…”