AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2 Validated as Myasthenia Gravis Biomarkers: A Comparative Proteomic Study With...

Myasthenia gravis (MG) lacks disease-specific biomarkers that can support monitoring of disease activity or guide treatment decisions. This study aimed to validate serum inflammatory proteins as MG-specific biomarkers by comparing their specificity to controls and individuals with other autoimmune neurological disorders, including multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP).

In this multicentre cross-sectional study, serum from 200 acetylcholine receptor antibody seropositive (AChR+) MG patients, 192 matched controls, 93 MS patients, and 51 CIDP patients was analyzed using a 92-plex inflammation panel (Olink PEA). Logistic regression, principal component analysis, and Boruta machine learning algorithms identified differentially expressed proteins. MG subgroups were defined by age at onset, disease severity, and immunosuppressive treatment.

Fourteen proteins significantly distinguished MG from controls, including AXIN1 (OR: 0.24), IL7 (OR: 9.38), ST1A1 (OR:0.42), IL10 (OR:3.62), CASP-8 (OR:1.61), and TNFSF14 (OR:0.50) (Bonferroni-corrected p < 0.00135). AXIN1, ST1A1, STAMBP, CDCP1, and SIRT2 were specific for MG, separating it from MS and CIDP. Shared markers across disorders included IL6, IL8, STAMBP, and TNFSF14. A 15-protein profile, including FGF-23 and CXCL9, correlated with MG severity. Subgroup analyses revealed distinct protein patterns by age and treatment. TRANCE and CD6 were reduced in immunosuppressed patients, whereas EN-RAGE, IL10, and TNFRSF9 varied in those receiving biologicals.

This study validates the MG-specific serum proteomic biomarkers AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2 and identifies signatures associated with severity, onset, and treatment. These findings support the use of blood-based biomarkers for monitoring and stratification in MG clinical trials and care.