Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

Qi Wu; Qin Wang; Jennifer Yang; Jacob Ws Martens; Elizabeth A Mills; Aiya Saad; Pavani Chilukuri; Catherine A Dowling; Yang Mao-Draayer

doi:10.1177/11795735211050712

Elevated sCD40L in Secondary Progressive Multiple Sclerosis in Comparison to Non-progressive Benign and Relapsing Remitting Multiple Sclerosis

J Cent Nerv Syst Dis. 2021 Oct 25:13:11795735211050712. doi: 10.1177/11795735211050712. eCollection 2021.

Authors

Qi Wu^{1

2}, Qin Wang^{1

2}, Jennifer Yang^{1

2}, Jacob Ws Martens^{1

2

3}, Elizabeth A Mills^{1

2}, Aiya Saad^{1

2}, Pavani Chilukuri^{1

2}, Catherine A Dowling^{1

2}, Yang Mao-Draayer^{1

2

3}

Affiliations

¹ Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
² Autoimmunity Center of Excellence, University of Michigan Medical School, Ann Arbor, MI, USA.
³ Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.

Abstract

Background: The long-term prognosis of relapsing-remitting multiple sclerosis (RRMS) is usually unfavorable as most patients transition to secondary progressive multiple sclerosis (SPMS) with accumulative disability. A rare form of non-progressive multiple sclerosis (MS) also exists, known as benign MS (BMS or NPMS), which lacks disease progression defined as Expanded Disability Status Scale (EDSS) ≤3 after 15 years of disease onset without treatment.

Purpose: Our study aims to identify soluble plasma factors predicting disease progression in multiple sclerosis (MS).

Research design and study sample: We utilized Luminex multiplex to analyze plasma levels of 33 soluble factors, comparing 32 SPMS patients to age-, sex-, and disease duration-matched non-progressive BMS patients, as well as to RRMS patients and healthy controls.

Results: Plasma levels of EGF, sCD40L, MCP1/CCL2, fractalkine/CX3CL1, IL-13, Eotaxin, TNFβ/LTα, and IL-12p40 were significantly different between the various types of MS. Plasma sCD40L was significantly elevated in SPMS compared to BMS and RRMS. The combination of MCP1/CCL2 and sCD40L discriminated between RRMS and SPMS. MCP1/CCL2 was found to be the most effective classifier between BMS and RRMS, while BMS was most effectively distinguished from SPMS by the combination of sCD40L and IFNγ levels.

Conclusions: These differences may facilitate personalized precision medicine and aid in the discovery of new therapeutic targets for disease progression through the improvement of patient stratification.

Keywords: Benign MS; multiple sclerosis; relapsing remitting MS; secondary progressive multiple sclerosis; soluble CD40 ligand.

Abstract

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