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News|Articles|May 14, 2026

Secondary Progressive MS Potentially Linked to Lower Serum Protein

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Key Takeaways

  • Retrospective longitudinal data linked declining serum albumin and total protein—measured roughly two years pre-conversion—to subsequent SPMS onset compared with contemporaneous RRMS controls.
  • Higher CSF IgG index at diagnosis appeared more frequent among those later developing SPMS, but the association did not reach statistical significance in this small cohort.
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The disease progression of patients with MS had an association with their serum protein level.

Monitoring strategies could be improved through the surveillance of serum protein levels, which have been linked to secondary progressive multiple sclerosis (SPMS), according to a new study published in Multiple Sclerosis and Related Disorders.1 Lower serum protein levels could come before the transition to SPMS in patients.

MS affects approximately 2.8 million people in the world and can cause weakness and trouble walking in those who live with the condition. Patients will start showing signs of relapsing-remitting MS (RRMS) but can transition into SPMS over time.2

However, how this transition occurs is not fully understood. Serum proteins could be a means of providing insight into the changes occurring in patients that are associated with chronic disease. This study aimed to evaluate whether the biomarkers of cerebrospinal fluid (CSF) measured at diagnosis and the changes in serum protein levels were associated with the progression from RRMS to SPMS.1

The observational study used data from the Neurology Service of the University Healthcare Complex of Salamanca between 1976 and 2019. Patients were split into RRMS and SPMS groups. Researchers extracted clinical data from medical records and used data on age at SPMS diagnosis, time from RRMS diagnosis to SPMS conversion, sex, current age, and Expanded Disability Status Scale (EDSS).

The researchers also included MRI from the most recent clinical evaluation for patients with RRMS or at the diagnosis of SPMS. Serum was analyzed 2 years before the SPMS diagnosis in the SPMS group or 2 years before the most recent measurement in the RRMS group and at the SPMS diagnosis or most recent measurement.

A total of 45 patients living with MS were included in the study, of which 23 patients were in the RRMS group, and 22 were in the SPMS group. The mean (SD) age was 55.7 (4.47) years in the RRMS group and 54.8 (7.18) years in the SPMS group. The RRMS group had a mean EDSS score of 1.96 (1.67) compared with 6.11 (0.86) in the SPMS group, which indicated more disability in the latter group.

CSF samples were evaluated for all patients, with those who later developed SPMS more often having a higher immunoglobulin G index compared with patients with RRMS. However, this was not found to be statistically significant. Serum samples were also evaluated for biomarkers 2 years before SPMS or the most recent evaluation for the RRMS group. Patients with SPMS had lower serum albumin levels before their progression compared with those with RRMS.

Patients with SPMS also had lower serum total protein concentrations. Both were found to have a significant association with disease progression. An inverse correlation was found between EDSS scores and serum total protein levels, indicating that greater disability was associated with lower serum protein concentration.

There were some limitations to this study. Biases are possible due to the retrospective design. Statistical power was limited, and subtle associations may not have been detected due to the small sample size. There was no standardized prospective protocol for collecting laboratory measurements. Biomarkers could have been influenced by disease-modifying therapies, but information about these therapies was not available.

The researchers concluded that a reduction in serum protein levels years before the clinical onset of SPMS may be possible and a possible indicator of disease progression.

“Although these biomarkers cannot yet be considered independent predictors of disease progression, their accessibility and low cost make them attractive candidates for incorporation into longitudinal monitoring strategies,” the authors concluded.

References

  1. Andreu LS, Martin JCV, Muñoz AH, et al. Longitudinal changes in serum protein levels are associated with disability progression in multiple sclerosis. Mult Scler Relat Disord. 2026;111:107246. doi:10.1016/j.msard.2026.107246
  2. Secondary progressive multiple sclerosis (SPMS). National Multiple Sclerosis Society. Accessed May 12, 2026. https://www.nationalmssociety.org/understanding-ms/what-is-ms/types-of-ms/secondary-progressive-ms

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