Background

Prevalence of chronic pulmonary aspergillosis (CPA) is ~3 million patients worldwide, and detection of Aspergillus-specific antibody is a critical diagnostic component. Some patients with CPA have subtle immune deficits possibly contributing to poor Aspergillus antibody production and false negative results.

Materials/methods

We analyzed patient data from 167 cases of clinically confirmed CPA previously evaluated by ImmunoCAP Aspergillus-specific IgG EIA, Bordier ELISA and LDBio Aspergillus IgG/IgM ICT lateral flow assay, to identify deficiencies in: mannose binding lectin (MBL), IgG, IgA, IgM, IFN gamma, IL12 or IL17 production, and/or low cell marker counts (CD4, CD19, CD56). We defined patients as ‘sero-negative’ if ImmunoCAP Aspergillus IgG was consistently and repeatedly negative (<40 mg A/L). ‘Sero-positive’ was defined as all other CPA cases.

Results

We found the rate of false negatives by ImmunoCAP Aspergillus IgG EIA (n = 23) to be more prevalent in patients with immunodeficiency markers, especially multiple defects. MBL deficiency combined with low CD19 cells (p < 0.001), pneumococcal antibody levels (p = 0.043), IgM (p = 0.047) or three combined (p = 0.001–0.018) or all four together (p = 0.018) were significant. The performance LDBio Aspergillus IgG/IgM ICT appears to be relatively unaffected by immunodeficiency (92.7% of ImmunoCap sero-negatives were positive). The Bordier assay performed significantly better than the ImmunoCAP assay (P = 0.0016) for sero-negative CPA cases.

Conclusions

In select cases of CPA, ImmunoCAP EIA yields a false negative result, making serological diagnosis difficult. ImmunoCAP false negatives are more prevalent in patients with multiple immunological defects, who may still be positive with the LDBio Aspergillus ICT or Bordier EIA.

中文翻译：

---

患者免疫缺陷对慢性肺曲霉病曲霉特异性抗体血清学检测诊断性能的影响

背景

全世界慢性肺曲霉病 (CPA) 的患病率约为 300 万，曲霉特异性抗体的检测是一个关键的诊断组成部分。一些 CPA 患者有轻微的免疫缺陷，可能导致曲霉抗体产生不良和假阴性结果。

材料/方法

我们分析了之前通过 ImmunoCAP曲霉特异性 IgG EIA、Bordier ELISA 和 LDBio Aspergillus IgG/IgM ICT 横向流动测定评估的 167 例临床确诊 CPA 的患者数据，以确定以下方面的缺陷：甘露糖结合凝集素 (MBL)、IgG、IgA、 IgM、IFN γ、IL12 或 IL17 产生，和/或低细胞标志物计数（CD4、CD19、CD56）。如果 ImmunoCAP曲霉IgG 持续且反复呈阴性（<40 mg A/L），我们将患者定义为“血清阴性” 。“血清阳性”被定义为所有其他 CPA 病例。

结果

我们发现 ImmunoCAP曲霉IgG EIA的假阴性率（n = 23）在具有免疫缺陷标志物的患者中更为普遍，尤其是多重缺陷。MBL 缺乏结合低 CD19 细胞 (p < 0.001)、肺炎球菌抗体水平 (p = 0.043)、IgM (p = 0.047) 或三者结合 (p = 0.001–0.018) 或所有这四种 (p = 0.018) 均显着。LDBio Aspergillus IgG/IgM ICT的性能似乎不受免疫缺陷的影响（92.7% 的 ImmunoCap 血清阴性呈阳性）。 对于血清阴性 CPA 病例，Bordier 测定的表现明显优于 ImmunoCAP 测定（P = 0.0016）。

结论

在特定的 CPA 病例中，ImmunoCAP EIA 会产生假阴性结果，使血清学诊断变得困难。ImmunoCAP 假阴性在具有多种免疫缺陷的患者中更为普遍，这些患者可能仍然对 LDBio Aspergillus ICT 或 Bordier EIA呈阳性。