Research in heterogeneity: New paper about patterns discrimination

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frodo
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Research in heterogeneity: New paper about patterns discrimination

Post by frodo » Tue Jan 21, 2020 1:18 am

New paper about discriminating the four pathological patterns:

The main idea is that there are four patterns of MS (one of them, IV very rare and often ignored), and they represent different pathogenic kinds of MS. Probably the most common, pattern II, is related to EBV while the rest are not. This paper says that there is an autoantibody signature for them.

Antibody signatures in patients with histopathologically defined multiple sclerosis patterns.

https://www.ncbi.nlm.nih.gov/pubmed/31950335

Abstract

Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I-III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complement deposition. In pattern III lesions, which include Baló's concentric sclerosis, primary oligodendrocyte damage was proposed. Serum antibody reactivities could reflect disease pathogenesis and thus distinguish histopathologically defined MS patterns. We established a customized microarray with more than 700 peptides that represent human and viral antigens potentially relevant for inflammatory demyelinating CNS diseases, and tested sera from 66 patients (pattern I n = 12; II n = 29; III n = 25, including 8 with Baló's), healthy controls, patients with Sjögren's syndrome and stroke patients. Cell-based assays were performed for aquaporin 1 (AQP1) and AQP4 antibody detection. No single peptide showed differential binding among study cohorts. Because antibodies can react with different peptides from one protein, we also analyzed groups of peptides. Patients with pattern II showed significantly higher reactivities to Nogo-A peptides as compared to patterns I (p = 0.02) and III (p = 0.02). Pattern III patients showed higher reactivities to AQP1 (compared to pattern I p = 0.002, pattern II p = 0.001) and varicella zoster virus (VZV, compared to pattern II p = 0.05). In patients with Baló's, AQP1 reactivity was also significantly higher compared to patients without Baló's (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Baló's patients showed loss of AQP1 and AQP4 in demyelinating lesions, but no antibodies binding conformational AQP1 or AQP4 were detected. In summary, higher reactivities to Nogo-A peptides in pattern II patients could be relevant for enhanced axonal repair and remyelination. Higher reactivities to AQP1 peptides in pattern III patients and its subgroup of Baló's patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation.

There is also a review here:

https://multiple-sclerosis-research.org ... t-targets/

Additional information (from other papers):

A description of the four patterns is available here:

Image

(Image taken from:Imaging in multiple sclerosis: A new spin on lesions, https://onlinelibrary.wiley.com/doi/ful ... 9485.12498)

As of 2018 it seems that pattern IV is currently considered outside the MS spectrum. The three remaining patterns evolve in a similar way and all the three can yield smouldering lesions. It is currently unknown what determines the evolution of a lesion. A better picture of the three remaining patterns could be this one:

Image

(Image taken from Reich et al NEJM 2018, linked through https://multiple-sclerosis-research.org ... ign-in-ms/ )
Last edited by frodo on Tue Jan 21, 2020 1:34 am, edited 5 times in total.

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frodo
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Previous papers about how to discriminate the patterns

Post by frodo » Tue Jan 21, 2020 1:23 am

Papers about tests for discriminating the patterns

-September 2019: Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry - IMG (imaging mass citometry) can discriminate the patterns.

- April 2018: Tissue Markers for Acute Multiple Sclerosis Treatment Response—A Step Toward Personalized Medicine: Personalized medicine tries to find the right medicine for each patient. Patterns are considered in this article.

- Feb. 2016: Patent for diagnosis of the MS subtype, able to discriminate patterns I and II. Methods and kits for diagnosing multiple sclerosis (MS) in a subject. Particularly, the present invention relates to methods and kits for diagnosing a subtype of MS in a subject, the subtype selected from relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and a pathologic sub-type of MS lesions selected from Pattern I and Pattern II MS lesion

- Dec. 2014: Predicting therapeutic efficacy of intravenous immunoglobulin IVIG in RRMS Pattern II, and therefore response to plasmapheresis, can be predicted from the genetic profile of a given patient.

- Oct. 2013: Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of MS Provides Clues for Environmental Triggers of the Disease. They report a strain of that bacteria in a pattern III lesion at that time known as "nascent lesion".

- June 2009: Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early MS. They say that in Pattern III there is evidence for reactive nitrogen species (RNS)‐mediated damage to oligodendrocytes.

- Nov. 2008: Review: Mitochondria and disease progression in multiple sclerosis. Reports about damage in mitochondria in pattern III MS and Balo's type lesions, where NAA is reduced and lactate is increased.

- Jul. 2008: Pattern III: Functionally important defects of mitochondrial respiratory chain complex IV are present in Pattern III but not in Pattern II multiple sclerosis lesions.(https://academic.oup.com/brain/article/ ... 722/387831)

- Pattern III: monocytes and microglia are differently activated in pattern II and III MS lesions
https://academic.oup.com/jnen/article/63/3/262/2916610

- Jun. 2003: A new paraclinical CSF marker for hypoxia‐like tissue damage in multiple sclerosis lesions: A monoclonal antibody against "canine distemper virus" detects a cross‐reactive endogenous brain epitope, able to discriminate pattern III.

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