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BMC Immunol. 2012; 13: 10.
Published online Mar 9, 2012. doi:  10.1186/1471-2172-13-10
PMCID: PMC3324382
Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies
Peng-Cheng Xu,#1,2 Shen-Ju Gou,#1 Xiao-Wei Yang,1 Zhao Cui,1 Xiao-Yu Jia,1 Min Chen,corresponding author1 and Ming-Hui Zhao1
1Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China
2Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin 300052, China
corresponding authorCorresponding author.
#Contributed equally.
Peng-Cheng Xu: nkxpc/at/163.com; Shen-Ju Gou: shenjugou/at/163.com; Xiao-Wei Yang: yangxw82/at/163.com; Zhao Cui: zhaocui78/at/163.com; Xiao-Yu Jia: jiaxiaoyu81/at/163.com; Min Chen: leimeng/at/public3.bta.net.cn; Ming-Hui Zhao: minghuizhao63/at/163.com
Received September 28, 2011; Accepted March 9, 2012.
Abstract
Background
The pathophysiological significance of variable region glycosylation of autoantibodies is still unclear. In the current study, the influence of the variable region N-linked oligosaccharides on the reactivity of three autoantibody specificities was investigated with Sambucus nigra agglutinin (SNA), which mainly binds to oligosaccharides with terminal α2, 6-linked sialic acid on the variable region of IgG.
Methods
Twenty-seven patients with serum positive anti-neutrophil cytoplasmic autoantibodies (ANCA) against myeploperoxidase (MPO) or proteinase 3 (PR3), or autoantibodies against glomerular basement membrane (GBM) were included. Total IgG was isolated and separated into non-SNA-binding and SNA-binding fractions with SNA affinity chromatography. Antigen-specific IgG was purified by immunoaffinity chromatography.
Results
At the same concentration of IgG, the antigen binding level of non-SNA-binding IgG was significantly lower than that of SNA-binding IgG for MPO-ANCA (absorbance value at 405 nm, 0.572 ± 0.590 vs. 0.962 ± 0.670, P < 0.001) and for PR3-ANCA (0.362 ± 0.530 vs. 0.560 ± 0.531, P = 0.003). The antigen binding level of non-SNA-binding IgG was significantly higher than that of SNA-binding IgG for anti-GBM antibodies (1.301 ± 0.594 vs. 1.172 ± 0.583, P = 0.044). The level of variable region glycosylation of total IgG was significantly lower than that of affinity-purified MPO-ANCA (1.021 ± 0.201 vs. 1.434 ± 0.134, P = 0.004). The level of variable region glycosylation of total IgG was significantly higher than that of affinity-purified anti-GBM antibodies (1.034 ± 0.340 vs. 0.734 ± 0.333, P = 0.007). The SNA-binding fraction of MPO-ANCA-containing IgG and PR3-ANCA-containing IgG induced higher levels of neutrophil oxygen radical production than the corresponding non-SNA-binding fractions (P < 0.001 and P = 0.043, respectively). The level of variable region glycosylation of affinity-purified MPO-ANCA was higher in active AAV than the same patients in remission (P = 0.001).
Conclusion
Characteristics of variable region glycosylation of ANCA and anti-GBM antibodies were different from that of total IgG, which might influence the antigen-binding ability of these antibodies. Variable region glycosylation of ANCA might influence the effect of ANCA-induced neutrophils respiratory burst.
Keywords: Glycosylation, Variable region, ANCA, Anti-GBM
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