Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual

Durante, Laurence; Zaaraoui, Wafaa; Rico, Audrey; Crespy, Lydie; Wybrecht, D.; Faivre, Anthony; Reuter, Françoise; Malikova, Irina; Pommier, Gilbert; Confort‐Gouny, Sylviane; Cozzone, Patrick J.; Ranjeva, Jean‐Philippe; Pelletier, Jean; Boucraut, José; Audoin, Bertrand

doi:10.1177/1352458511424589

Cited by 29 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of the few studies that explored relationship between the CSF outcomes and disease activity, they did not investigate QAlb, did not include brain atrophy measures, were of a limited sample size, cross-sectional nature or employed a short follow-up period. [17][18][19][20][21][22] The results showed a relationship between baseline QAlb and increased T2-LV, T2 lesion and CEL number at clinical onset supporting the association between BBB permeability and inflammatory processes in MS.…”

Section: Discussionmentioning

confidence: 81%

“…21,22 In addition, there are only few MRI studies investigating the relationship between i.t. production of IgM and lesion formation in MS, [18][19][20] and no study investigating the relationship between IgM production and brain atrophy. Results of our study support previous findings documenting increased accumulation of T2 lesions and CELs in subjects with i.t.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later

et al. 2015

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In patients with CIS, the identification of CSF lipid-specific IgM OCB was associated with greater MRI lesion load and brain atrophy at the first clinical event [249] and with an aggressive disease course [250] . Periventricular lesion load during the first years of disease proved to be related as well to the entity of IgM intrathecal synthesis in CIS patients, so that an active role of IgM in the development of demyelinating lesions has been supposed [251] .…”

Section: Igm Oligoclonal Bandsmentioning

confidence: 95%

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

View full text Add to dashboard Cite

For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

show abstract

“…Immunoglobulin G (IgG) and IgM antibodies are major contributors to the OCBs formation in the CSF (Ziemssen and Ziemssen, 2005;Ziemssen et al, 2019). Elevated intrathecal IgM synthesis, but not other immunoglobulins, has been suggested to predict a worse disease evolution since the early MS stages, being associated in patients with a more disability progression and with a more aggressive form of the disease (Walsh and Tourtellotte, 1986;Villar et al, 2002Villar et al, , 2003Cepok et al, 2006;Durante et al, 2012;Beltrán et al, 2014;Frau et al, 2018). In patients with clinically isolated syndrome (CIS), IgM OCB detection was associated with higher risks of conversion to clinically definite MS and in relapsing-remitting (RRMS) patients predicted a higher probability of converting to secondary progressive MS (Villar et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Magliozzi

Mazziotti

Montibeller

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Background: Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated. Methods: Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up. Results: A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p = 0.013). CSF IgM levels correlated with higher CSF levels of CXCL13 (p = 0.039), CCL21 (p = 0.023), interleukin 10 (IL-10) (p = 0.025), IL-12p70 (p = 0.020), CX3CL1 (p = 0.036), and CHI3L1 (p = 0.048) and were associated with earlier age of patients at diagnosis (p = 0.008), white matter lesion (WML) number (p = 0.039) and disease activity (p = 0.033) after 2 years of follow-up. Conclusion: IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course.

show abstract

Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual

Abstract: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation.

Cited by 29 publications

References 25 publications

Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later

Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients

Contact Info

Product

Resources

About