Three biomarkers of DMT adverse effects proposed

 

A new review has summarized three potential biomarkers of adverse effects that may occur with disease-modifying therapies used in the treatment of MS (Kreft et al. J Neurol 2022;269:5192-5193). (Free references below.) All results are preliminary and further validation is required.

1. Lymphopenia associated with dimethyl fumarate (DMF): A small study (N=31) identified that a decrease in a subpopulation of Th effector memory cells (expressing CCR4, CD25, CD103 and IL10) was predictive of lymphopenia during treatment with DMF (predictive value 74%) (Diebold et al. Ann Neurol 2022;91:676-681). Patients who developed lymphopenia also showed a relative increase in myeloid and B cells.

2. Distinguishing MS lesions from natalizumab-associated PML: A pilot study used PET imaging with the mitochondrial translocator protein (TSPO) radioligand 18F-GE-180 in conjunction with 3T MRI (Mahler et al. Brain 2021;144:2683-2695). TSPO is a non-specific marker of inflammation. It is increased both in PML and MS lesions but the pattern is different: reticular accumulation of TSPO-expressing phagocytes in PML vs. a more homogeneous distribution in MS lesions. PET imaging detected enhanced TSPO uptake in PML lesions early on (even before Gd enhancement) and up to 52 months after PML diagnosis; the latter may be useful for long-term follow-up. Analysis of these differences in TSPO signals was 96% accurate in differentiating PML from MS lesions.

3. Predicting secondary autoimmunity after alemtuzumab: An exploratory study reported that patients with a higher percentage of B cells (mainly plasmablasts and plasma cells) at baseline had a higher risk of developing secondary autoimmunity (Walo-Delgado et al. Front Immunol 2021;12:760546). A baseline value >0.10% was associated with a higher risk of autoimmunity (OR 5.91); this cut-off was even more predictive when natalizumab-treated patients were excluded (OR 11.67). At-risk patients also had a higher value of CD8+ T cells producing TNF-alpha. At one year after alemtuzumab initiation, the predictive value of a low proportion of plasmablasts/plasma cells was 75%.

Further reading:

Kreft et al. Free full text at  www.ncbi.nlm.nih.gov/pmc/articles/PMC9363281/pdf/415_2022_Article_11300.pdf

Diebold et al. Free full text at
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314128/pdf/ANA-91-676.pdf

Mahler et al. Free full text at
https://academic.oup.com/brain/article/144/9/2683/6184141

Walo-Delgado et al. Free full text at
https://www.frontiersin.org/articles/10.3389/fimmu.2021.760546/full

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