|Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies|
|Xu, Peng-Cheng1,2; Gou, Shen-Ju1; Yang, Xiao-Wei1; Cui, Zhao1; Jia, Xiao-Yu1; Chen, Min1; Zhao, Ming-Hui1|
|关键词||Glycosylation Variable Region Anca Anti-gbm|
|WOS标题词||Science & Technology|
|关键词[WOS]||IMMUNOGLOBULIN-G ; SOMATIC HYPERMUTATION ; RHEUMATOID-ARTHRITIS ; SYSTEMIC VASCULITIS ; MONOCLONAL-ANTIBODY ; REGION CARBOHYDRATE ; MASS-SPECTROMETRY ; HUMAN GERMLINE ; SUGAR CHAINS ; SERUM IGG|
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 alpha 2, 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.
|项目编号||2012CB517702 ; 30972733 ; 81021004|
|资助机构||Chinese 973 project ; National Natural Science Fund|
|作者单位||1.Peking Univ, Key Lab Renal Dis, Minist Hlth China, Renal Div,Dept Med,Hosp 1,Inst Nephrol, Beijing 100034, Peoples R China|
2.Tianjin Med Univ, Gen Hosp, Dept Nephrol, Tianjin 300052, Peoples R China
|Xu, Peng-Cheng,Gou, Shen-Ju,Yang, Xiao-Wei,et al. Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies[J]. BMC IMMUNOLOGY,2012,13.|
|APA||Xu, Peng-Cheng.,Gou, Shen-Ju.,Yang, Xiao-Wei.,Cui, Zhao.,Jia, Xiao-Yu.,...&Zhao, Ming-Hui.(2012).Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies.BMC IMMUNOLOGY,13.|
|MLA||Xu, Peng-Cheng,et al."Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies".BMC IMMUNOLOGY 13(2012).|