. 2017 Jun 20;6:566. Originally published 2017 Apr 25. [Version 2] doi: 10.12688/f1000research.11349.2

Table 1. From clinical assessment to application of systems biology in MS.

Networks	BASED ON
NEDA status ²⁵ • NEDA 1–3 • NEDA 4 • NEDA 5 • NEDA 6 • NEDA 7 • NEDA 8	Clinical event, EDSS, MRI Brain atrophy Cognitive impairment CSF neurofilament level Patients related outcome Oligoclonal bands
BIOMARKERS ^7, 8 Related to cells, structures, metabolic pathways, and inflammatory and degenerative cascades.	OCB, NAA, Glutamate, IL-12, IL-23, Enolase, NfL, CXCL13, IL-8, ATP break down products, GFAP, MMP9, MMP3, Th17, Th1/Th17, Chitinase 3, IFN-ϒ, TNF-α, Fetuin-A, Osteopontin, PET (microglia), non-conventional MRI. Others.
NEURO-IMMUNO-PATHOLOGY	Tissue damage resulting from interaction of neurons, glial cells, immune system cells (B & T-cell lymphocytes, macrophages, dendritic cells), cytokines and antibodies in the CNS
GENETIC DETERMINANTS ⁸	HLA-DRB11501: • risk for MS • early disease onset. • risk for progression from RRMS to SPMS HLA-DPB1 0501 & HLA-DPB1* 0301: • risk for opticospinal MS. HLA-DRB1* 1501 & HLA-DQB1* 0301: • worst brain atrophy measures. DR3 & DR4 haplotypes: • risk for MS. TOB1 gen: • early conversion from CIS to CDMS. ApoEƐ4: • greater risk for mental disorders. Pharmacogenomics
GUT-IMMUNE-BRAIN AXIS ²⁶ The gut-associated lymphoid tissue system (GALT) is located in the intestinal lamina propria, near the epithelium, and consists of: Organized cellular complexes • Peyer’s patches • solitary lymphoid follicles Dispersed cells • T and B cells, macrophages, and dendritic cells	The human intestinal flora (microbiota) interaction with GALT could be considered harmless, beneficial or pathogenic depending on the anti-inflammatory or pro-inflammatory state that could result from this interaction. In the later, it could influence immunity and inflammation in the pathophysiology of MS.

The table shows the dynamic interaction of networks leading to the molecular expression of MS in the preclinical state and through disease span.

Abbreviations in the table: EDSS: Expanded Disability Status Scale; OCB: oligoclonal bands; NAA: N-Acetyl aspartate; IL: interleukin; NfL: light chain sub-unit of neurofilaments; CXCL13: C-X-C Motif Chemokine Ligand 13; ATP: adenosine triphosphate; GFAP: glial fibrillary acidic protein; MMP: matrix metalloproteinase; Th17: IL-17 secreting T-lymphocyte; IFN-ϒ: interferon gamma; TNFα: tumor necrosis factor α; CIS: clinical isolated syndrome; CDMS: clinical definitive multiple sclerosis