The use of cytokine signature patterns: separating drug naïve, interferon and natalizumab-treated multiple sclerosis patients

Abstract

Multiple sclerosis (MS) is an inflammatory illness characterized by demyelination and axonal neurodegeneration. Here, we used serum samples from MS patients to demonstrate if "cytokine signature" patterns can separate different patient groups better than using single cytokines. In this case, we used cytokine profiling to demonstrate if "cytokine signature" patterns can separate MS patients treated with interferon or natalizumab from drug naïve patients. Serum levels of eight individual cytokines (TNFα, IFNγ, S100B, IL-1β, IL-6, IL-8, IL-17 and IL-23) in MS patients treated with interferons (n = 11) and natalizumab (n = 14) were measured and, in general, showed reduced levels compared to drug naïve MS patients (n = 12). More evident changes were seen when analyzing "cytokine signatures" (i.e. summed value of all eight cytokines), which showed that patients treated with natalizumab and interferons showed significantly reduced cytokine signature levels than drug naïve MS patients. Moreover, patients treated with natalizumab were separated from drug naïve patients by almost 100% fidelity and that patients treated with natalizumab also had reduced levels of pro-inflammatory cytokines compared to patients treated with interferon. Overall, this study provides an example showing that the use of "cytokine signatures" may provide benefits over the analysis of single cytokines for the development of potential biomarkers.

S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis

“…Along with astrocytic and microglial activation, demyelination is accompanied by exacerbated production of proinflammatory cytokines and an increased production of inflammasome-related proteins [19,28]. This inflammatory milieu is crucial for determination of lesion extent, immune cell recruitment and ability to remyelinate.…”

“…More recently, Petzold and collaborators showed the presence of S100B in acute lesions of post-mortem brain tissue of patients with relapsing-remitting multiple sclerosis (RRMS) [16], while it was shown to be increased in CSF [17] or serum of MS patients, decreasing after immunosuppressive [18] or natalizumab [19] therapies. However, no further studies clarified the role of S100B and its receptor RAGE in different stages of MS lesions or on disease progression.…”

Cytokines in Multiple Sclerosis – Possible Targets for Immune Therapies

“…Circulating plasma levels of some cytokines (GM-CSF, TNF-alpha, IL-6 and IL-10) were also found decreased after one year of treatment [24]. Significantly lower serum concentrations of pro-inflammatory cytokines TNF-alpha, IFN-gamma, IL1beta, IL-6, IL-17 and IL-23 were found in natalizumabtreated MS patients compared to drug-naïve or IFN-betatreated ones [25].…”

Modulation of TLR3/TLR4 inflammatory signaling by the GABAB receptor agonist baclofen in glia and immune cells: relevance to therapeutic effects in multiple sclerosis

“…The concentrations of cytokines/chemokines are altered in MS ( Ubogu et al, 2006 ), suggesting that cytokine/chemokine signatures may indicate disease progression in patient groups ( O’Connell et al, 2014 ). Given that evidence indicates that TNF-α ( Sharief and Hentges, 1991 ) and IL-8 ( Lund et al, 2004 ) are higher in serum of patients with MS, we examined the relative expression of TNF-α and IL-8 in plasma isolated from newly diagnosed RR-MS patients.…”