Intrathecal immunoreactivity in people with or without previous infectious mononucleosis

Jons, Daniel; Zetterberg, Henrik; Malmeström, Clas; Bergström, Tomas; Axelsson, Markus; Blennow, Kaj; Thulin, Måns; Sundström, Peter; Andersen, Oluf

doi:10.1111/ane.13280

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…Decay of the IM cellular reaction is slow and remains ongoing after one year (Hadinoto et al, 2008). Indeed, increased intrathecal cytokine activity has been reported approximately a decade after IM (Jons et al, 2020). Occasional, specific, and persistent changes after IM have been proposed to be essential for the development of MS (Ruprecht, 2020).…”

Section: Introductionmentioning

confidence: 99%

Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis

Jons¹,

Berg

Sundström

et al. 2021

Multiple Sclerosis and Related Disorders

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Background: : A two-to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM. Methods: : Sera were obtained from individuals with acute IM from 2003-2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS.Results: : The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group. Conclusion: : In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.

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Section: Introductionmentioning

confidence: 99%

Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis

Jons¹,

Berg

Sundström

et al. 2021

Multiple Sclerosis and Related Disorders

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show abstract

“…Considering the infectious mononucleosis (IM) as a non-genetic risk factor for MS, Jons et al assayed MS-relevant CSF cyto- or chemokines from non-MS individuals with or without previous IM and MS people as a reference group. They found a stepwise inflammation from IM sequelae to an MS endophenotype in a subgroup of IM patients, which shows CSF changes comparable to those of the MS reference group ( 50 ).…”

Section: Incidental Mri Findings or Subclinical Ms? The Contribution ...mentioning

confidence: 76%

Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis

et al. 2022

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Following the extraordinary progress in the treatment of multiple sclerosis (MS), two major unmet needs remain: understanding the etiology of the disease and, hence, designing definitive cures (this perspective is neither at hand, nor it can be taken for granted that the etiologic targets will be readily treatable); the prevention of an overt and disabling disease, which seems to be a more realistic and pragmatic perspective, as the integration of genetic data with endophenotypes, MRI, and other biomarkers ameliorates our ability to identify early neuroinflammation. Radiologically isolated syndrome (RIS; diagnosed when the unanticipated MRI finding of brain spatial dissemination of focal white matter lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations) and the recently focused “prodromal MS” are conditions at risk of conversion toward overt disease. Here, we explore the possibility of secondary prevention approaches in these early stages of neuroinflammation. RIS and prodromal MS are rare conditions, which suggest the importance of Study Groups and Disease Registry to implement informative clinical trials. We summarize ongoing preventive approaches in the early stages of the demyelinating process, especially in RIS conditions. Moreover, we highlight the importance of the biomarkers and the predictors of evolution to overt disease, which may be useful to select the individuals at risk of conversion to clinically isolated syndrome (CIS) and/or clinically definite MS. Finally, we illustrate the importance of the endophenotypes to test the frontline immunomodulatory approach for preventive strategies. Future investigations, especially in relatives of patients, based on MRI techniques and biological studies (better with integrated approaches) may provide opportunities to understand the MS early causal cascade and may help to identify a “therapeutic window” to potentially reverse early disease processes.

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Intrathecal immunoreactivity in people with or without previous infectious mononucleosis

Cited by 2 publications

References 37 publications

Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis

Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis

Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis

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