Serum levels of IgM to phosphatidylcholine predict the response of multiple sclerosis patients to natalizumab or IFN-β

Abstract

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.

Morphological profiling of T cells predicts clinical response to VLA-4-targeting natalizumab therapy in patients with multiple sclerosis

“…For that purpose, we evaluated morphology, velocity, and straightness of CD8 + T cells from four patients from each treatment response subgroup, upon interaction with VCAM-1 in an under-agarose setting to prevent nonspecific cell displacements. T cells tended to form homotopic aggregates upon natalizumab exposure (Figure 5G), as previously reported for other anti-VLA-4 antibodies 19,30 , but this phenomenon appeared to impact comparably T cells from both subgroups (Figure 5H). Analysis of cell area confirmed that T cells from non-responders tend to be resistant to the reduction of cell spreading evoked by natalizumab (Figure 5I).…”

“…Currently, 30% of RRMS patients treated with natalizumab present evidence of disease activity 17 , not satisfactorily responding to the treatment according to the NEDA criteria. VLA-4 expression on Peripheral Blood Mononuclear Cells (PBMCs) 18 , serum levels of IgM specific for phosphatidylcholine 19 , metalloproteinases 20 , low percentage of CD5 + B cells 21 , age at prescription and disease duration 22 have been pointed as biological parameters related to natalizumab clinical response, although their robustness as predictive biomarkers remains to be established. To date, we therefore lack a pretreatment test to predict whether a given person with MS might benefit from the therapy.…”

IgM to phosphatidylcholine in multiple sclerosis patients: from the diagnosis to the treatment

“…We demonstrated that those with the highest levels of IgMPC responded subsequently to natalizumab. 78 This was expected because these patients have an aggressive course, with more relapses and faster increase of the disability, and they do not respond to first-line therapies. 78…”

“…In other words, the detection of IgMPC in serum samples is a diagnostic marker in this disease and has numerous advantages compared with the detection of OIgGBs. 73,78 It is an easily reproducible technique; it can be automatable, and it does not use CSF.…”

“…78 This was expected because these patients have an aggressive course, with more relapses and faster increase of the disability, and they do not respond to first-line therapies. 78…”