Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies.
Influence of variable domain glycosylation on anti-neutrophil cytoplasmic autoantibodies and anti-glomerular basement membrane autoantibodies.
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可变结构域糖基化对抗中性粒细胞胞质自身抗体和抗肾小球基底膜自身抗体的影响
DOI：
10.1186/1471-2172-13-10
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发表时间：
2012-03-09
期刊：
影响因子：
3
通讯作者：
Zhao MH
中科院分区：
文献类型：
--
作者：
Xu PC;Gou SJ;Yang XW;Cui Z;Jia XY;Chen M;Zhao MH
背景自身抗体可变区糖基化的病理生理学意义尚不清楚。在本研究中，用主要与末端α2，方法对27例血清抗中性粒细胞胞浆自身抗体（ANCA）阳性的髓过氧化物酶（MPO）或蛋白酶3（PR 3）或抗肾小球基底膜（GBM）的自身抗体。分离总IgG，并用SNA亲和层析将其分离成非SNA结合级分和SNA结合级分。结果在相同的IgG浓度下，非SNA结合IgG对MPO ANCA的抗原结合水平显著低于SNA结合IgG（405 nm处吸光度值为0.572 ± 0.590 vs. PR3-ANCA（0.362 ± 0.530vs. 0.560 ± 0.531，P = 0.003）。非SNA结合IgG的抗GBM抗体结合水平显著高于SNA结合IgG（1.301 ± 0.594vs. 1.172 ± 0.583，P = 0.044）。总IgG的可变区糖基化水平显著低于亲和纯化的MPO-ANCA（1.021 ± 0.201vs. 1.434 ± 0.134，P = 0.004）。总IgG的可变区糖基化水平显著高于亲和纯化的抗GBM抗体（1.034 ± 0.340vs. 0.734 ± 0.333，P = 0.007）。含有MPO-ANCA的IgG和含有PR 3-ANCA的IgG的SNA结合部分比相应的非SNA结合部分诱导更高水平的中性粒细胞氧自由基产生（分别为P < 0.001和P = 0.043）。结论ANCA抗体和抗GBM抗体的可变区糖基化特征与总IgG不同，可能影响了这些抗体的抗原结合能力。ANCA可变区糖基化可能影响ANCA诱导中性粒细胞呼吸爆发的作用。
BackgroundThe 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.MethodsTwenty-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.ResultsAt 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 ± 0.590vs. 0.962 ± 0.670, P < 0.001) and for PR3-ANCA (0.362 ± 0.530vs. 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 ± 0.594vs. 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 ± 0.201vs. 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 ± 0.340vs. 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).ConclusionCharacteristics 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.
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影响因子：
5.4
作者：
COX, JPL;TOMLINSON, IM;WINTER, G
通讯作者：
WINTER, G
影响因子：
4.6
作者：
Holland, M;Takada, K;Jefferis, R
通讯作者：
Jefferis, R
影响因子：
3
作者：
Dalziel, M;McFarlane, I;Axford, JS
通讯作者：
Axford, JS
影响因子：
4.4
作者：
Gala, FA;Morrison, SL
通讯作者：
Morrison, SL
影响因子：
4.3
作者：
DONADEL, G;CALABRO, A;HARINDRANATH, N
通讯作者：
HARINDRANATH, N