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Assessing serum IgG4 glycosylation profiles of IgG4-related disease using lectin microarray
Chaojun Hu1, Panpan Zhang1, Liubing Li2
1Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Objectives:
IgG4 related disease (IgG4-RD) is a multiorgan fibroinflammatory disorder. Lectin microarray is a high-throughput glycosylation analysis technology. The aim of our study was to investigate glycosylation profiling of serum IgG4 from IgG4-RD patients and controls.
Methods:
A large cohort of 167 IgG4-RD patients, 130 disease controls (DCs) and 86 healthy controls (HCs) were included in the current study. The glycan level of serum IgG4 of all participants was determined by lectin microarray. A verification assay of lectin microarray and lectin blot were used to clarify the relationship between the serum IgG4 and purified IgG4 glycosylation.
Results:
The results revealed that the glycan level of mannose (binding MNA-M, VVA mannose, ConA) was significantly increased and that the glycan level of fucose (binding LTL), GlcNAc (binding DSL), GalNAc (binding HPA) was significantly decreased in IgG4-RD patients compared to DCs and HCs. We further found that the glycan level of GlcNAc was positively correlated with that of complement 3 (C3), and that the reduced level of GlcNAc was associated with damage to multiple organs. In addition, the mannose level (binding MNA-M and VVA mannose) was negatively correlated with C3 and complement 4 (C4) levels.
Conclusions:
Serum IgG4 of IgG4-RD patients exhibits different glycosylation levels. This study demonstrated that there is important clinical value in identifying aberrant GlcNAc levels as a potential diagnostic index for multi-organ involvement. Furthermore, the mannose level of serum IgG4 may reflect the degree of inflammation of IgG4-RD.
