High-throughput investigation of molecular and cellular biomarkers in NMOSD

Abstract

ObjectiveTo identify candidate biomarkers associated with neuromyelitis optica spectrum disorder (NMOSD) using high-throughput technologies that broadly assay the concentrations of serum analytes and frequencies of immune cell subsets.MethodsSera, peripheral blood mononuclear cells (PBMCs), and matched clinical data from participants with NMOSD and healthy controls (HCs) were obtained from the Collaborative International Research in Clinical and Longitudinal Experience Study NMOSD biorepository. Flow cytometry panels were used to measure the frequencies of 39 T-cell, B-cell, regulatory T-cell, monocyte, natural killer (NK) cell, and dendritic cell subsets in unstimulated PBMCs. In parallel, multiplex proteomics assays were used to measure 46 serum cytokines and chemokines in 2 independent NMOSD and HC cohorts. Multivariable regression models were used to assess molecular and cellular profiles in NMOSD compared with HC.ResultsNMOSD samples had a lower frequency of CD16+CD56+ NK cells. Both serum cohorts and multivariable logistic regression revealed increased levels of B-cell activating factor associated with NMOSD. Interleukin 6, CCL22, and CCL3 were also elevated in 1 NMOSD cohort of the 2 analyzed. Multivariable linear regression of serum analyte levels revealed a correlation between CX3CL1 (fractalkine) levels and the number of days since most recent disease relapse.ConclusionsIntegrative analyses of cytokines, chemokines, and immune cells in participants with NMOSD and HCs provide congruence with previously identified biomarkers of NMOSD and highlight CD16+CD56+ NK cells and CX3CL1 as potential novel biomarker candidates.

Dynamic Changes in AQP4-IgG Level and Immunological Markers During Protein-A Immunoadsorption Therapy for NMOSD: A Case Report and Literature Review

“…A marked increase of the T cell and B cell counts was observed after the therapy ( Table 2 ), with a reduced proportion of the activated T (CD3+HLA-DR+) and Ts cells (CD3+CD8+HLA-DR+), implying a possibly improved immune system, which could be a downstream effect after the clearance of the pro-inflammatory mediators. In contrast, the percent and number of NK cells had a pronounced drop, which was also noted by previous studies as a potential biomarker candidate for acute-phase NMOSD ( 19 , 20 ), although the underlying cause has been still unclear. A significantly increased level of Tregs (CD3+CD4+CD25+CD127low+) after immunoadsorption treatment in a previous study ( 21 ) was not found in our case.…”

Distinct Immunological Features of Inflammatory Demyelinating Diseases of the Central Nervous System

“…Besides, in our study, the counts of WBCs, neutrophils, and monocytes were elevated, suggesting a systemically activated immune system triggered by the severe episodes or prodromal infections in patients with MOGAD, especially in those presenting with acute disseminated encephalomyelitis. A significantly reduced NK-cell level seemed specific for NMOSD when compared to MS and MOGAD, which was also observed by previous studies [28,29]. Nevertheless, the underlying cause of this finding has been still an enigma due to a paucity of T cells and NK cells in or around the NMO lesions [21], although NK cells may participate in the development of NMOSD by antibodydependent cellular cytotoxicity [30].…”

“…A significantly reduced NK-cell level seemed specific for NMOSD when compared to MS and MOGAD, which was also observed by previous studies [28, 29]. Nevertheless, the underlying cause of this finding has been still an enigma due to a paucity of T cells and NK cells in or around the NMO lesions [21], although NK cells may participate in the development of NMOSD by antibody-dependent cellular cytotoxicity [30].…”

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

“…While major advances in the knowledge of NMOSD pathophysiology have led to investigating the efficacy of targeted treatments in phase III clinical trials, further elucidation of the immunopathogenesis of AQP4+ NMOSD may lead to novel treatment approaches. Besides IL-6, CCL22 and CCL3, CD16 + CD56 + NK cells and CX3CL1 have been identified as potential novel biomarker candidates [ 46 ]. Besides the assessment of the frequency of various immune cell types [ 46 ], their functional characteristics need further exploration.…”

“…Besides IL-6, CCL22 and CCL3, CD16 + CD56 + NK cells and CX3CL1 have been identified as potential novel biomarker candidates [ 46 ]. Besides the assessment of the frequency of various immune cell types [ 46 ], their functional characteristics need further exploration. For instance, the role and function of antigen-presenting cells, such as dendritic cells, have not been clarified so far.…”