ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Nutrients. 2023 Dec 12;15(24):5083. doi: 10.3390/nu15245083.
Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only two converted from seronegative to seropositive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN = 4 units/mL) vs. tTG-IgA (non-recombinant, ULN = 20 units). There is a strong correlation between both measurements as evidenced by a Pearson coefficient of R = 0.8584; however, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of three instead of four for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.
血清组织转谷氨酰胺酶(tTG)免疫球蛋白 A(IgA)和脱酰胺麦胶蛋白肽(DGP)IgA 和免疫球蛋白 G(IgG)的检测是诊断乳糜泻(CeD)和监测无麸质饮食(GFD)依从性的标志性检测,目前是治疗 CeD 的唯一方法。本研究解决了两个问题:(i)恢复含麸质饮食的 CeD 患者血清学阳性复发;(ii)接近正常上限(ULN)指定阈值的两种不同 tTG-IgA 检测之间的相关性。关于第一个问题,通常将疑似 CeD 的个体重新置于麸质饮食中以恢复其血清学水平。然而,我们表明,需要大量的麸质才能使血清学恢复为阳性水平。例如,在一项对 22 名接受安慰剂治疗并在 6 周内摄入 84 克麸质的患者的研究中,只有两名患者的 tTG-IgA 从血清阴性转为血清阳性。关于第二个主题,我们比较了不同血清学检测的关系,即 tTG-IgA AB(重组,ULN = 4 单位/mL)与 tTG-IgA(非重组,ULN = 20 单位)。正如 Pearson 系数 R = 0.8584 所证明的那样,两种测量之间存在很强的相关性;然而,我们观察到,通过将 tTG-IgA AB(重组)检测的 ULN 值从 4 调整为 3,在灵敏度和特异性方面的交叉相关性有了显著改善。这一结果表明,在尚未开始 GFD 的患者中,用于初始诊断的检测阈值可能需要根据监测情况和诊断性麸质挑战进行调整。