Serum CXCL5 as a biomarker in multiple sclerosis and neuromyelitis optica spectrum disorder.

OBJECTIVE: Our aim was to determine whether serum C-X-C motif chemokine 5 (CXCL5) may serve as a diagnostic biomarker for relapsing-remitting multiple sclerosis (RRMS) as well as a marker that can be used to predict treatment response. METHODS: CXCL5 levels were measured by ELISA in sera of 20 RRMS patients under fingolimod treatment, 10 neuromyelitis optica spectrum disorder (NMOSD) patients, 15 RRMS patients presenting predominantly with spinal cord and optic nerve attacks (MS-SCON), and 14 healthy controls. RESULTS: Fingolimod treatment significantly reduced CXCL5 levels. CXCL5 levels were comparable among NMOSD and MS-SCON patients. CONCLUSION: Fingolimod might regulate the innate immune system. Serum CXCL5 measurement does not differentiate between RRMS and NMOSD.

Impact of fingolimod on CD4+ T cell subset and cytokine profile of relapsing remitting multiple sclerosis patients.

Fingolimod inhibits the egress of lymphocytes from lymphatic tissues and also directly affects their functions by modulation of the sphingosine-1-phosphate receptor 1 (S1P1). Our aim was to evaluate the impact of fingolimod on diverse CD4+ T cell subsets, and cytokines. Sixty-six relapsing remitting multiple sclerosis (RRMS) patients were treated with oral fingolimod (0.5 mg) for 6 months, and blood samples were collected at baseline, 3 months, and 6 months. Serum levels of seven cytokines and five chemokines were measured by multiplex immunoassay, and frequencies of peripheral blood mononuclear cell subsets were assessed by flow cytometry, and compared with those of 60 healthy controls. CCL2 (p = 0.039), and CCL5 (p = 0.001) levels were significantly higher in fingolimod-treated patients than healthy controls, whereas end-of-study serum levels of IL-6, IL-8, IL-17A, IL-22, IL-23, TNF-α, CXCL10, and CXCL13 were comparable to the baseline levels. Six months of fingolimod treatment reduced CD3+ T cell (mean ±â€¯standard deviation, 72.9% ±â€¯5.5 vs. 60.1% ±â€¯11.1, p < 0.001), CD4+ T cell (62.2% ±â€¯8.5 vs. 24.6% ±â€¯12.9, p < 0.001), CD4+CD25hi regulatory T cell (Treg) (3.4% ±â€¯1.3 vs. 2.0% ±â€¯1.4, p < 0.01), and CD19+ B cell (13.2% ±â€¯5.8 vs. 5.3% ±â€¯2.7, p < 0.001) frequencies, while CD8+ T cells (31.8% ±â€¯7.8 vs. 57.8% ±â€¯13.2, p < 0.001) were increased, and NK and NKT cells remained unchanged. The proportions of intracytoplasmic IL-4, IL-10, IFN-γ, and TNF-α-producing T cells were increased, whereas IL-17-producing cells remained relatively constant as measured by flow cytometry. Fingolimod appears to primarily diminish lymphocyte subsets involved in antigen presentation (CD19+ B and CD4+ T cells) rather than immune cells (CD8+ T, NK, and NKT cells) in charge of host defense against pathogens. In contrast, a relative increase is observed in pro- and anti-inflammatory cytokine-producing T helper subsets (IFN-γ, TNF-α, IL-4, and IL-10-producing CD4+ T cells), suggesting that effector T cells are suppressed to a lesser degree by S1P1 modulation.

Peripheral nerve hyperexcitability syndromes.

Peripheral nerve hyperexcitability (PNH) syndromes can be subclassified as primary and secondary. The main primary PNH syndromes are neuromyotonia, cramp-fasciculation syndrome (CFS), and Morvan's syndrome, which cause widespread symptoms and signs without the association of an evident peripheral nerve disease. Their major symptoms are muscle twitching and stiffness, which differ only in severity between neuromyotonia and CFS. Cramps, pseudomyotonia, hyperhidrosis, and some other autonomic abnormalities, as well as mild positive sensory phenomena, can be seen in several patients. Symptoms reflecting the involvement of the central nervous system occur in Morvan's syndrome. Secondary PNH syndromes are generally seen in patients with focal or diffuse diseases affecting the peripheral nervous system. The PNH-related symptoms and signs are generally found incidentally during clinical or electrodiagnostic examinations. The electrophysiological findings that are very useful in the diagnosis of PNH are myokymic and neuromyotonic discharges in needle electromyography along with some additional indicators of increased nerve fiber excitability. Based on clinicopathological and etiological associations, PNH syndromes can also be classified as immune mediated, genetic, and those caused by other miscellaneous factors. There has been an increasing awareness on the role of voltage-gated potassium channel complex autoimmunity in primary PNH pathogenesis. Then again, a long list of toxic compounds and genetic factors has also been implicated in development of PNH. The management of primary PNH syndromes comprises symptomatic treatment with anticonvulsant drugs, immune modulation if necessary, and treatment of possible associated dysimmune and/or malignant conditions.