Abstract
ObjectivePrimary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease whose diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in PBC patients using high-throughput lectin microarrays technology.MethodLectin microarray containing 56 lectins was used to detect and analyze the expression of serum IgG glycosylation in 99 PBC patients, 70 disease controls (DCs), and 38 healthy controls (HCs). Significant differences in PBC from control groups as well as across PBC subgroups positive for various autoantibodies were explored and verified by lectin blot technique.ResultsLectin microarray detection revealed that compared to DC and HC groups, the specific glycan level of serum IgG sialic acid in PBC patients was increased. For each PBC subgroup, glycan levels of IgG mannose and galactose were decreased in AMA-M2 positive PBC patients compared to the AMA-M2 negative group. IgG N-Acetylgalactosamine (GalNAc) and fucose were decreased in anti-sp100 positive patients. IgG galactose was increased in anti-gp210 positive patients. IgG mannose was decreased in ACA-positive patients. Although the difference in overall sialic acid level was not observed using lectin blot, all results among the above PBC subgroups were consistent with the results of the technique.ConclusionLectin microarray is an effective and reliable technique for analyzing glycan structure. PBC patients positive for different autoantibody exhibits distinct glycan profile. Altered levels of glycosylation may be related to the occurrence and development of the disease, which could provide a direction for new biomarker identification.
Highlights
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive nonsuppurative inflammation and destruction of the small and medium-sized bile ducts, resulting in fibrosis, cirrhosis, and eventual liver failure [1, 2]
Serum samples of 99 PBC patients, 70 disease controls (DCs) patients, and 38 healthy controls were detected by lectin microarray
Compared with the DC and healthy controls (HCs) groups, serum Immunoglobulin G (IgG) from PBC patients had a higher affinity for SSA
Summary
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive nonsuppurative inflammation and destruction of the small and medium-sized bile ducts, resulting in fibrosis, cirrhosis, and eventual liver failure [1, 2]. The sensitivity and specificity of AMA detection for PBC are both >90%, it has been reported that 5–10% of patients with PBC were not positive for AMA [9]. In the ANA category, research has shown that antinuclear dot antibodies sp100 and antinuclear pore antibodies gp210 are specific biomarkers in PBC serum [9, 14, 15], and they can reduce AMA-negative cases by less than 5% in PBC [16]. Findings indicate that anti-SP100 antibody has an important diagnostic role in AMA-negative PBC patients, while anti-gp210 has the best predictive value regarding progression to end-stage hepatic failure [7, 13]. Several studies indicate that ACA positivity in patients with PBC has significant predictive value for progression to portal hypertension [17, 18]. New approaches to identifying more specific biomarkers in PBC are needed [20]
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