Site-specific N-glycosylation of alpha-2-macroglobulin reflects the progression of Schistosoma japonicum-induced liver fibrosis

Schistosomiasis leads to liver fibrosis through an egg-induced granulomatous inflammatory response in the host. Although parasite glycosylation is known to contribute to immune evasion and pathogenesis, alterations in host protein glycosylation during infection progression and liver fibrosis development remain poorly understood. Using a rabbit model specifically established to study Schistosoma japonicum -induced liver fibrosis (SjLF), we performed comprehensive glycoprofiling of serum glycomes and glycoproteomes via lectin microarrays and high-resolution mass spectrometry. Our analysis revealed dynamic changes in N-glycosylation of proteins involved in the humoral immune response, with particular emphasis on site-specific glycosylation of alpha-2-macroglobulin (A2M). Ten glycosylation sites on A2M were identified, exhibiting significant variations across different stages of infection and liver fibrosis in SjLF, suggesting their potential as indicators for monitoring SjLF progression. Further validation demonstrated that the N ₁₄₂₄ QT glycosylation site of human A2M in clinical serum samples serves as a promising diagnostic biomarker for SjLF, underscoring the value of targeted glycoproteomics in precise disease monitoring. This study provides insights into host glycosylation remodeling during SjLF and highlights its critical role in schistosome–host interactions.