Highlights
- •Tumour necrosis factor inhibitors and other rheumatoid arthritis treatments can infrequently induce demyelination disease.
- •Disease modifying anti-rheumatoid drugs may increase pathogenic memory B cell responses and inhibit potentially pathogenic ectopic B cell follicles.
- •Poor central nervous penetration of disease modifying anti-rheumatoid drugs may not limit brain located ectopic B cell follicles, whilst inhibiting joint disease
Abstract
Background
Perhaps the most informative experiments in human disease are clinical trials and
notably, responses to specific therapies can be highly-informative to help understand
disease pathogenesis. There are reagents that inhibit a variety of different autoimmune
conditions, such as CD20 memory B cell depleters that are active in both multiple
sclerosis (MS), rheumatoid arthritis (RA) and other conditions, suggesting influences
on common immune mechanisms in different diseases. However, a notable exception seemed
to be the use of tumour necrosis factor (TNF) inhibitors that limits RA, yet seem
to, rarely, trigger demyelination and induce MS. This was first seen with TNF-inhibiting
monoclonal antibodies and TNF-receptor-immunoglobulin fusion proteins. However, this
is also seen with tyrosine and Janus kinase inhibitors that inhibit RA, yet induce
demyelinating disease in some individuals
Purpose
To provide an overview, from a B cell centric perspective, that may underpin the biology
that links arthritis treatments to the development of demyelinating disease.
Conclusions
It is apparent that the disease modifying anti-rheumatoid drugs that cause demyelination
share a number of common features. These agents tend to inhibit TNF-receptor signalling,
augment or exhibit limited inhibitor activity on class-switched memory B cells and
importantly appear to be relatively excluded from the central nervous system (CNS).
They will thus not target ectopic B cell follicles in the CNS, unlike that occurring
in peripheral autoimmunity as seen with anti-TNF treatments in RA. Agents such as
ibudilast and some Janus kinase inhibitors that inhibit TNF and clearly penetrate
the CNS do not appear to induce demyelination and may even be neuroprotective. It
remains to be established whether selection or development of CNS penetrant agents
may avoid CNS-complications of treatments for RA. Clearly, further studies are warranted
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
CNS (central nervous system (CNS)), CSF (cerebrospinal fluid), DMARDS (disease modifying anti-rheumatoid drugs), MS (multiple sclerosis, rheumatoid, arthritis, TNF, tumour necrosis factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: May 31, 2021
Accepted:
May 27,
2021
Received in revised form:
May 20,
2021
Received:
April 12,
2021
Identification
Copyright
© 2021 Published by Elsevier B.V.
