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Multiple sclerosis (MS) is an inflammatory demyelinating disease with unknown etiology. Various proteinases have been observed in increased levels in the central nervous system of patients with MS, which may contribute to the release of immunogenic myelin components. α 2 -Macroglobulin (α 2 M) inhibits a broad spectrum of proteinases sterically, undergoing major conformational changes induced by the proteinases themselves. Moreover, α 2 M acts as a carrier of several cytokines in the systemic circulation. By use of radial immunodiffusion, we determined the total α 2 M levels in plasma from 28 MS patients and 15 control subjects [14 patients with other neurologic diseases (OND) and one healthy individual]. No significant differences in total α 2 M concentration were observed between the MS patients and the control subjects. A comparison of the degree of α 2 M transformation in MS patients with different disease courses and controls was performed, using monoclonal antibodies (mAbs) specific for binding to native and transformed α 2 M, respectively. The fractions of transformed α 2 M were significantly increased in patients with secondary or primary progressive disease course compared with the controls. No significant differences were obtained using a native-specific mAb. At least a major proportion of α 2 M from the MS patients was able to change conformation from its native to its transformed state, as demonstrated by a shift in mAb reactivity, following methylamine treatment of the plasma samples. In conclusion, the results indicate that plasma α 2 M may be inactivated at a higher degree in patients with chronic progressive MS compared with patients with OND. This may influence the levels of proteinases and cytokines in the systemic circulation and may furthermore have diagnostic implications. [ABSTRACT FROM AUTHOR]

Objectives: The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction., Materials and Methods: We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference., Results: The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (P of binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic., Conclusions: These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis., Materials and Methods: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA., Results: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance., Conclusion: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)