TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients

Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system, where immune dysregulation plays a critical role. We sought to explore the modulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFɑ) and TNF-like weak inducer of apoptosis (TWEAK), along with their respective autoantibodies, TNAb and TWAb, and to decipher potential associations between these and clinical characteristics which could assist personalized therapy in MS. We also assessed the complementarity to leading candidate biomarkers in MS patient monitoring, namely, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). Serum levels of these cytokines and their autoantibodies were measured in 150 MS patients and 186 healthy controls (HC) by ELISA. We found that sTWEAK levels were significantly higher, while sTNFɑ levels were lower in MS patients compared to HC. Additionally, we detected TWAb in 10% of MS patients, a prevalence significantly higher than in HC (4%) and TNAb in only one patient. TWAb-positive patients were significantly younger, had lower EDSS scores, a shorter disease duration, and predominantly presented with the relapsing–remitting form of MS. Together, these results provide new actors to be considered in the development of a biomarker profiling panel to be used in MS patient management. Further research is warranted to elucidate the clinical significance of these autoantibodies and their role in MS neuroinflammatory modulation.