Currently, different CNS diseases independently tend to be investigated, however, it might be relevant to investigate potential biomarkers throughout a variety of neurological diseases to better understand their role in the CNS pathology. Supporting information S1 FigThe distribution of the median fold-changes during treatment were greatly affected by immunoglobulins that are target for somatic rearrangement (TSR-immunoglobulins) (antibodies). Relapsing-remitting multiple sclerosis (RRMS) is commonly treated by anti-inflammatory drugs, where one of the most effective drugs to date is the monoclonal antibody natalizumab. Methods The cerebrospinal fluid (CSF) proteome was analyzed in 56 patients with RRMS before and after natalizumab treatment, using label-free mass spectrometry and a subset of the changed proteins were verified by parallel reaction monitoring in a new cohort of 20 patients, confirming the majority of observed changes. Results A total of 287 differentially abundant proteins were detected including (i) the decrease of Amikacin disulfate proteins with roles in immunity, such as immunoglobulin heavy constant mu, chitinase-3-like protein 1 and chitotriosidase, (ii) an increase of proteins involved in metabolism, such as lactate dehydrogenase A and B and malate-dehydrogenase cytoplasmic, and (iii) an increase of proteins associated with the central nervous system, including lactadherin and amyloid precursor protein. Comparison with the CSF-PR database provided evidence that natalizumab counters protein changes commonly observed in RRMS. Furthermore, vitamin-D binding protein and apolipoprotein 1 and 2 were unchanged during treatment with natalizumab, implying that these may be involved in disease activity unaffected by natalizumab. Conclusions Our study revealed that some of the previously suggested biomarkers for MS were affected by the natalizumab treatment while others were not. Proteins not previously suggested as biomarkers were also found affected by the treatment. In sum, the results provide new information on how the natalizumab treatment impacts the CSF proteome of MS patients, and points towards processes affected by the treatment. These findings ought to be explored further to disclose potential novel disease mechanisms and predict treatment responses. Background Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) causing widespread inflammation and neurodegeneration in the brain and spinal cord. The disease course is heterogeneous, and the rate and disability progression depend on both the subtype of the disease and on the therapy provided. Relapsing-remitting multiple sclerosis (RRMS) is the most common course, affecting about 85C90% of patients [1, 2]. Patients diagnosed with RRMS experience repeated episodes of CNS dysfunction, usually initially followed by partial or full remission. If not effectively treated, accumulating disability will usually appear along the disease course, and a substantial proportion convert to a secondary progressive course (SPMS) with gradual worsening without remission. Fewer patients (10C15%) experience a gradual worsening (without recovery) from the beginning of the disease, called primary progressive MS (PPMS) [3]. These clinical events are likely caused by disturbance in self-tolerance in peripheral immune cells that are recruited across the blood-brain barrier and damage CNS myelin, leading to disrupted neuronal signal conduction and clinical symptoms depending on the site of damage in the brain or spinal cord [2]. Several disease modifying therapies (DMTs) in RRMS have anti-inflammatory effects, thereby suppressing clinical relapses and disease progression. One such drug, natalizumab (Tysabri?), is a humanized monoclonal antibody that binds to the 41 integrin on leucocytes and hinders their recruitment across the blood brain barrier. Treatment with natalizumab effectively reduces inflammation and clinical relapses in the CNS [4] but is also associated with increased risk of opportunistic infections in the CNS, especially progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV) [5]. Due to this risk, natalizumab is usually restricted to the treatment of more severe MS, or to JCV-negative patients [1, 6]. In Rabbit polyclonal to ACVR2B this study, we used label-free LC-MS to analyze changes in the CSF proteome during natalizumab Amikacin disulfate therapy after approximately two years of treatment. This provided insight into the effects of the drug on the CSF proteome and thereby also suggesting possible biomarkers for treatment response and mechanism of Amikacin disulfate action in RRMS. Methods Patient selection Approval for the study was given by the Ethics Committee of General Amikacin disulfate University Hospital in Prague (Nr. 1976/17 S-IV) and written informed consent was obtained from all patients. For the Bergen location, the study was approved by.