IgG Glycosylation Profiling of Peripheral Artery Diseases with Lectin Microarray

Area of Science:

• Biochemistry
• Immunology
• Vascular Biology

Background:

• Inflammation is a key driver in atherosclerotic plaque progression for peripheral artery disease (PAD).
• Immunoglobulin G (IgG) glycosylation influences immune functions and serves as a potential biomarker for various diseases.

Purpose of the Study:

• To investigate serum IgG glycosylation profiles in patients with lower-extremity peripheral artery disease (LEPAD), carotid artery stenosis (CAS), and abdominal aortic aneurysm (AAA).
• To explore the association of IgG glycosylation patterns with clinical parameters and disease severity in PAD.

Main Methods:

• Serum IgG glycosylation was analyzed using lectin microarray in LEPAD, CAS, AAA patients, and healthy controls.
• Lectin blot was employed for validating observed glycosylation differences.

Main Results:

• LEPAD and AAA patients exhibited significantly higher Sambucus nigra agglutinin (SNA) binding (sialic acid) compared to CAS patients.
• Elevated Concanavalin A (ConA) and Pisum sativum agglutinin (PSA) binding (mannose and fucose) were noted in LEPAD versus CAS.
• Specific glycosylation patterns correlated with clinical factors like dyslipidemia, Fontaine severity, diabetes, hypertension, high-sensitivity C-reactive protein (hsCRP), total cholesterol, and creatinine levels.

Conclusions:

• Increased SNA and ConA binding in LEPAD patients suggests potential diagnostic utility.
• Mannose-rich IgG N-glycans and bisecting GlcNAc are associated with disease severity and diabetes in LEPAD, respectively.
• IgG glycosylation alterations are implicated in PAD pathogenesis and progression, with associations found between hsCRP, creatinine, and specific glycan structures.