Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
Clin Exp Rheumatol. 2009 Jan-Feb;27(1 Suppl 52):S45-52.
The glycosylation status of autoantigens appears to be crucial for the pathogenesis of some autoimmune diseases, since carbohydrates play a crucial role in the distinction of self from non-self. Proteinase 3 (PR3), the main target antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis (WG), contains two Asn-linked glycosylation sites. The present study explores the influence of the glycosylation status of PR3 on the PR3 recognition by ANCA in a well characterized population of patients with WG.
Forty-four patients with WG (459 serum samples) who participated in a multicenter randomized trial, were tested by capture ELISA for ANCA against PR3 and deglycosylated recombinant variants of PR3.
The patients were followed for a median of 27 months, and the median number of serum samples per patient was 10. At baseline, the correlation between the levels of ANCA against PR3 and against all the deglycosylated recombinant variants of PR3 were greater than 0.94 (?<0.001 for all the comparisons). Longitudinal analyses comparing the levels of ANCA against PR3 versus all the deglycosylated recombinant variants of PR3, using linear mixed models, showed no significant statistical differences (rho >or=0.90 in all cases).
The glycosylation status of PR3 has no impact on its recognition by ANCA in WG.
自身抗原的糖基化状态似乎对某些自身免疫性疾病的发病机制至关重要，因为碳水化合物在区分自我和非我方面起着至关重要的作用。蛋白酶 3（PR3）是 Wegener 肉芽肿（WG）患者抗中性粒细胞胞质抗体（ANCA）的主要靶抗原，它包含两个天冬酰胺连接的糖基化位点。本研究探讨了 PR3 的糖基化状态对 ANCA 识别 PR3 的影响，该研究在一个具有特征的 WG 患者人群中进行。
44 名参加多中心随机试验的 WG 患者（459 份血清样本）通过捕获 ELISA 检测针对 PR3 的 ANCA 和 PR3 的去糖基化重组变体。
患者中位随访时间为 27 个月，每位患者的中位血清样本数为 10 个。在基线时，针对 PR3 的 ANCA 水平与针对所有去糖基化的 PR3 重组变体的水平之间的相关性大于 0.94（所有比较的 P 值均<0.001）。使用线性混合模型对针对 PR3 的 ANCA 水平与针对所有去糖基化的 PR3 重组变体的水平进行纵向分析，结果显示无统计学差异（所有情况下 rho 值均≥0.90）。
PR3 的糖基化状态对 WG 中的 ANCA 识别没有影响。
