Predicting natalizumab response

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The story starts with the observation that certain types of antibody are found in MS and their presence is associated with evidence of antibody activation that causes damage. This antibody type is called IgM which is often the first type of antibody produced. They found that many people with MS showed antibody responses to phosphotidylcholine (PC) . They suggest that serum IgM-PC is a candidate biomarker for early inflammatory stages of MS.

Sadaba et al. 2020 C=control MS= yep MS https://pubmed.ncbi.nlm.nih.gov/32518205/

So what is phosphotidylcholine?

Phosphatidylcholine is a major constituent of cell membranes and is found in the outer leaflet of a cell membrane. It is a lipid (fat). It is found all over the body and so one suspects the antibodies are a consequence rather than a cause so I initially thought that as as damage occurs if stimulates an antibody. However this is not likely because in this study there are higher, not lower, the reponders had higher levels of antibody levels of antibodies to phosphatidylcholine in natalizumab treated verses glatiramer acetate treated individuals., So

Muñoz Ú, Sebal C, Escudero E, Urcelay E, Arroyo R, García-Martínez MA, Quintana FJ, Álvarez-Lafuente R, Sádaba MC. Serum levels of IgM to phosphatidylcholine predict the response of multiple sclerosis patients to natalizumab or IFN-β. Sci Rep. 2022 Aug 3;12(1):13357

We developed an ELISA assay demonstrating the high prevalence of serum IgM to phosphatidylcholine (IgM-PC) in the first stages of multiple sclerosis (MS). We aimed to analyze the role of serum IgM-PC as a biomarker of response to treatment. Paired serum samples from 95 MS patients were obtained before (b.t) and after (a.t) treatment with disease modifying therapies. Patients were classified as non-responders or responders to treatment, according to classical criteria. Serum IgM-PC concentration was analyzed using our house ELISA assay. The level of serum IgM-PC b.t was higher in patients treated later with natalizumab than in those treated with Copaxone (p = 0.011) or interferon-β (p = 0.009). Responders to natalizumab showed higher concentration of serum IgM-PC b.t than those who did not respond to it (p = 0.019). The 73.3% of patients with the highest level of serum IgM-PC b.t responded to natalizumab. IgM-PC level decreased a.t in both cases, non-responders and responders to natalizumab. IgM-PC levels a.t did not decrease in non-responders to interferon-β, but in responders to it the IgM-PC level decreased (p = 0.007). Serum IgM-PC could be a biomarker of response to natalizumab or interferon-β treatment. Further studies would be necessary to validate these results.

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