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Record W4386069245 · doi:10.1111/sji.13325

Relapsing/remitting multiple sclerosis: A speculative model and its implications for a novel treatment

2023· article· en· W4386069245 on OpenAlexaff
Peter A. Bretscher

Bibliographic record

VenueScandinavian Journal of Immunology · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsUniversity of Saskatchewan
Fundersnot available
KeywordsMultiple sclerosisImmune systemAntigenImmunologySubclassInflammatory responseInflammationMedicineBiologyAntibody

Abstract

fetched live from OpenAlex

The clinical pattern in relapsing/remitting multiple sclerosis may be accounted for if an autoreactive immune response can transition back and forth between inflammatory, pathogenic, and non-inflammatory, non-pathogenic modes. Such 'back-and-forth' immune responses are rare. I speculate how such back-and-forth immune responses may arise. Understanding the nature of these different modes, and what controls their mutual transition, may help in designing strategies to favour the nonpathogenic mode, thus constituting treatment. Antigen dose is known to be critical in determining the class/subclass of primary immune responses. Observations have led us to suggest the level of antigen also similarly influences the class/subclass of on-going immune responses. I propose the relapsing, inflammatory and the remitting modes are respectively sustained by relatively low and high amounts of the responsible autoantigens, as is the case, for example, for Th1 and Th2 responses to foreign antigens. In addition, I propose more self-antigens are released during an inflammatory than during a remitting mode. The decrease in the amount of antigen released, as the response transitions from an inflammatory to a remitting mode, results in time in a decreased level of antigen and so the response again evolves towards the inflammatory mode. The inflammatory mode then leads to an increased release of antigen and so, in time, to remission. This model thus explains the transition between different modes. I outline non-invasive, testable predictions of the hypothesis. If confirmed, it may be ethical to examine whether the non-inflammatory mode can be sustained by administering myelin antigens during the remitting phase.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.214
Threshold uncertainty score0.991

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.071
GPT teacher head0.276
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2023
Admission routes1
Has abstractyes

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