Wiesner Olaf, Russell Kimberly A, Lee Augustine S, Jenne Dieter E, Trimarchi Matteo, Gregorini Gina, Specks Ulrich
Mayo Clinic, Rochester, MN 55905, USA.
Arthritis Rheum. 2004 Sep;50(9):2954-65. doi: 10.1002/art.20479.
Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL.
HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen.
Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA-negative, as were sera obtained from healthy controls.
Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.
人中性粒细胞弹性蛋白酶（HNE）和蛋白酶3（PR3）在结构和功能上相关。PR3是韦格纳肉芽肿（WG）中抗中性粒细胞胞浆抗体（ANCA）的主要靶抗原。在WG和其他自身免疫性疾病中，报道的HNE ANCA频率范围为0%至20%。我们之前在可卡因诱导的中线破坏性病变（CIMDL）患者中检测到了HNE ANCA。我们检验了以下假设：血管炎患者中报道的HNE ANCA频率差异可能与检测方法的差异有关，并且HNE ANCA可能是CIMDL的一个标志物。
对25例CIMDL患者的HNE ANCA反应性进行了表征，并与604例连续患者（64例WG患者、14例显微镜下多血管炎[MPA]患者和526例其他患者）的对照队列以及45名健康志愿者进行了比较。使用一种先前未描述的重组HNE表达系统通过间接免疫荧光法以及使用纯化的天然HNE作为靶抗原通过直接和捕获酶联免疫吸附测定法来检测HNE ANCA。
在CIMDL患者中，84%的患者通过1种检测方法可检测到HNE ANCA，68%的患者通过2种检测方法可检测到，36%的患者通过所有3种检测方法均可检测到。57%的HNE ANCA阳性CIMDL血清通过至少1种检测方法也为PR3 ANCA阳性。相比之下，604份对照血清中只有8份（1.3%）通过至少1种检测方法与HNE反应，3份（0.5%）通过2种检测方法反应，只有1份血清样本（0.16%）通过所有3种检测方法反应。从WG或MPA患者获得的血清普遍为HNE ANCA阴性，健康对照者的血清也是如此。
对HNE ANCA的最佳敏感性需要多模态检测。HNE ANCA在CIMDL中很常见，但在其他自身免疫性疾病中不常见，包括经典的ANCA相关血管炎。HNE ANCA可能有助于区分CIMDL和WG，而PR3 ANCA的阳性检测结果可能无法区分。
