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Anti-SPAG16 antibodies in primary progressive multiple sclerosis are associated with an elevated progression index
L de Bock1, J Fraussen1, L M Villar2
1Biomedical Research Institute and Transnationale Universiteit Limburg, Hasselt University, Diepenbeek, Belgium.
Background And Purpose:
Sperm-associated antigen 16 (SPAG16), a sperm protein which is upregulated in reactive astrocytes in multiple sclerosis (MS) lesions, has recently been identified as a novel autoantibody target in MS. The aim of this study was to investigate whether anti-SPAG16 antibody levels differ between MS subtypes (relapsing-remitting, RR; primary or secondary progressive, PP, SP) and whether antibody positivity is associated with clinical characteristics.
Methods:
Plasma anti-SPAG16 antibody levels were determined by recombinant protein enzyme-linked immunosorbent assay (ELISA) in 374 MS patients (274 RRMS, 39 SPMS and 61 PPMS) and 106 healthy controls.
Results:
Significantly elevated anti-SPAG16 antibodies were found in 22% of MS patients with 93% specificity. Anti-SPAG16 seropositivity was associated with an increased Expanded Disability Status Scale (EDSS) in overall MS. A higher proportion of PPMS patients showed anti-SPAG16 antibody reactivity (34%) compared to RRMS (19%) and SPMS (26%), and presented with higher anti-SPAG16 antibody levels. Seropositive PPMS patients had a significantly increased progression index compared to seronegative patients.
Conclusions:
Anti-SPAG16 antibodies are associated with an increased EDSS in overall MS, indicating that they are linked to a worse MS disease outcome. Moreover, the presence of anti-SPAG16 antibodies may be a biomarker for a more severe disease in PPMS patients, as indicated by an increased progression index.
Insights
Anti-SPAG16 antibodies are linked to worse outcomes in multiple sclerosis (MS). Higher levels are found in primary progressive MS (PPMS) and correlate with increased disability and disease progression.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Autoimmunity in Neurological Diseases
Background:
- Sperm-associated antigen 16 (SPAG16) is upregulated in multiple sclerosis (MS) lesions.
- SPAG16 is a novel autoantibody target identified in MS patients.
- Investigating anti-SPAG16 antibodies may reveal insights into MS pathogenesis and progression.
Purpose of the Study:
- To determine if anti-SPAG16 antibody levels differ across MS subtypes (RRMS, SPMS, PPMS).
- To assess the association between anti-SPAG16 antibody positivity and clinical characteristics in MS.
- To evaluate anti-SPAG16 antibodies as a potential biomarker for MS severity.
Main Methods:
- Plasma anti-SPAG16 antibody levels were measured using enzyme-linked immunosorbent assay (ELISA).
- The study included 374 MS patients (274 RRMS, 39 SPMS, 61 PPMS) and 106 healthy controls.
- Antibody levels and seropositivity were correlated with Expanded Disability Status Scale (EDSS) and progression index.
Main Results:
- Elevated anti-SPAG16 antibodies were detected in 22% of MS patients with 93% specificity.
- Anti-SPAG16 seropositivity correlated with a higher EDSS in overall MS.
- Primary progressive MS (PPMS) patients showed higher anti-SPAG16 antibody proportions (34%) and levels, with seropositive patients having increased progression.
Conclusions:
- Anti-SPAG16 antibodies are associated with increased disability (EDSS) in MS, suggesting a worse disease outcome.
- Anti-SPAG16 antibodies may serve as a biomarker for more severe disease, particularly in PPMS.
- Further research into anti-SPAG16 antibodies could inform therapeutic strategies for progressive MS.
