Marzinotto Ilaria, Dottori Ludovica, Baldaro Francesca, Dilaghi Emanuele, Brigatti Cristina, Bazzigaluppi Elena, Esposito Gianluca, Davidson Howard W, Piemonti Lorenzo, Lampasona Vito, Lahner Edith
San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy.
J Transl Autoimmun. 2021 Nov 1;4:100131. doi: 10.1016/j.jtauto.2021.100131. eCollection 2021.
Corpus atrophic gastritis (CAG) may lead to intrinsic factor (IF) deficiency and vitamin B malabsorption. Intrinsic factor autoantibodies (IFA) are considered markers of pernicious anemia, but their clinical utility in CAG has not been evaluated. This study aimed to assess IFA in CAG patients and controls using a luciferase immunoprecipitation system (LIPS).
Recombinant nanoluciferase-tagged IF secreted from transfected Expi293F cells was used as antigen in an IFA-LIPS assay. IFA IgG were measured in sera from subjects undergoing gastroscopy and biopsy (updated Sydney system) mainly for anemia (57%) or dyspepsia (34%). This cohort comprised 105 patients with histologically-proven-CAG (cases: median age 64 years, 68% females) and 110 subjects with suspected CAG that were histologically negative (controls: median age 67 years, 54% females). Cut-off values were selected by Q-Q-plot analysis (negative: <2.5 arbitrary units).
IFA levels were higher in cases than in controls (Mann-Whitney:p < 10). The ROC-AUC was 0.67 (95%CI 0.60-0.73, p < 0.0001). The IFA LIPS sensitivity and specificity for CAG were 32% (95% CI 24-42) and 95% (95% CI 90-99). This diagnostic performance remained similar after stratification for the presence/absence of anemia, dyspepsia or vitamin B deficiency. IFA levels were higher in females compared with males (p = 0.0127). In females aged <65 years, IFA-positives were more prevalent than in males (43.5% vs 6.6%, p = 0.011).
The IFA-LIPS assay discriminated between CAG patients and controls showing a good specificity (95%) at the cost of sensitivity (32%). IFA-positivity occurred independently from anemia and vitamin B deficiency, but was more frequent in younger females. IFA testing should be considered in patients at high clinical suspicion of CAG.
萎缩性胃炎（CAG）可能导致内因子（IF）缺乏和维生素B吸收不良。内因子自身抗体（IFA）被认为是恶性贫血的标志物，但其在CAG中的临床应用尚未得到评估。本研究旨在使用荧光素酶免疫沉淀系统（LIPS）评估CAG患者和对照中的IFA。
转染的Expi293F细胞分泌的重组纳米荧光素酶标记的IF用作IFA-LIPS检测中的抗原。在主要因贫血（57%）或消化不良（34%）接受胃镜检查和活检（更新的悉尼系统）的受试者血清中测量IFA IgG。该队列包括105例经组织学证实为CAG的患者（病例：中位年龄64岁，68%为女性）和110例组织学阴性的疑似CAG受试者（对照：中位年龄67岁，54%为女性）。通过Q-Q图分析选择临界值（阴性：<2.5任意单位）。
病例组的IFA水平高于对照组（Mann-Whitney检验：p < 0.0001）。ROC曲线下面积为0.67（95%CI 0.60 - 0.73，p < 0.0001）。IFA LIPS对CAG的敏感性和特异性分别为32%（95%CI 24 - 42）和95%（95%CI 90 - 99）。在根据贫血、消化不良或维生素B缺乏的有无进行分层后，这种诊断性能保持相似。女性的IFA水平高于男性（p = 0.0127）。在年龄<65岁的女性中，IFA阳性比男性更普遍（43.5%对6.6%，p = 0.011）。
IFA-LIPS检测能够区分CAG患者和对照，显示出良好的特异性（95%），但敏感性较低（32%）。IFA阳性独立于贫血和维生素B缺乏发生，但在年轻女性中更常见。对于临床高度怀疑CAG的患者，应考虑进行IFA检测。
