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非霍奇金淋巴瘤患者的乳糜泻筛查:基于血清抗转谷氨酰胺酶的方法。

Screening for celiac disease in non-Hodgkin's lymphoma patients: a serum anti-transglutaminase-based approach.

作者信息

Carroccio Antonio, Iannitto Emilio, Di Prima Lidia, Cirrincione Sonia, Troncone Riccardo, Paparo Franco, Trapani Lydia Gianni, Gucciardi Antonio, Averna Maurizio R, Montalto Giuseppe, Notarbartolo Alberto

机构信息

Department of Internal Medicine, University Hospital of Palermo, Palermo, Italy.

出版信息

Dig Dis Sci. 2003 Aug;48(8):1530-6. doi: 10.1023/a:1024811707311.

DOI:10.1023/a:1024811707311
PMID:12924648
Abstract

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.

摘要

多项研究表明,乳糜泻(CD)与非霍奇金淋巴瘤(NHL)之间存在关联。我们的目的是评估血清抗组织转谷氨酰胺酶(抗tTG)抗体检测在连续的NHL患者中筛查CD的效用。总共纳入了80例新诊断为NHL的连续患者(中位年龄61岁)。为了比较CD的发生率和抗tTG检测的阳性结果,我们招募了500名献血者。在所有患者中,用两种不同的酶联免疫吸附测定(ELISA)法检测血清抗tTG:一种以豚鼠tTG(gp - tTG)为基础,另一种以人重组t - TG(h - tTG)为抗原。还检测了血清抗肌内膜抗体(EmA)。血清EmA和/或抗tTG呈阳性的受试者接受肠道活检以进行组织学研究、HLA - DQ表型测定和血清抗麦醇溶蛋白(AGA)检测。80例NHL患者中有8例(10%)抗tTG ELISA呈阳性——其中2例仅抗gp - tTG呈阳性,6例抗h - tTG呈阳性(7.5%)。80例NHL患者中血清EmA均为阴性。献血者对照组中抗tTG阳性的发生率为2/500(0.4%),显著低于NHL患者中的发生率(P < 0.0001)。这两名抗tTG阳性的献血者均被发现患有CD。仅1例抗h - tTG阳性的NHL患者存在肠黏膜萎缩,随访确诊为CD(NHL患者中CD的发生率为1.2%;与献血者相比:P = 0.4)。在其他7例抗tTG阳性的NHL患者中,虽然有4例观察到固有层有炎性浸润,但肠道结构正常。包括被诊断为CD的患者在内,没有抗tTG阳性的NHL患者有CD家族史,且所有患者体重正常,无吸收不良迹象。抗tTG假阳性结果与血清自身抗体阳性频率较高和T细胞型NHL相关。总之,在NHL患者中,抗tTG检测结果与EmA检测结果常常不一致,抗tTG用于CD诊断时假阳性结果频率较高。

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本文引用的文献

1
Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: a prospective study.抗组织转谷氨酰胺酶ELISA与抗肌内膜抗体检测在乳糜泻诊断中的比较:一项前瞻性研究
Clin Chem. 2002 Sep;48(9):1546-50.
2
Risk of non-Hodgkin lymphoma in celiac disease.乳糜泻患者患非霍奇金淋巴瘤的风险。
JAMA. 2002 Mar 20;287(11):1413-9. doi: 10.1001/jama.287.11.1413.
3
Celiac sprue.乳糜泻
巴西圣保罗州里贝朗普雷图献血者中乳糜泻的患病率及人口统计学特征。
Dig Dis Sci. 2006 May;51(5):1020-5. doi: 10.1007/s10620-006-9340-9. Epub 2006 Jun 7.
N Engl J Med. 2002 Jan 17;346(3):180-8. doi: 10.1056/NEJMra010852.
4
Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease.豚鼠转谷氨酰胺酶免疫连接测定不能预测慢性肝病患者的乳糜泻。
Gut. 2001 Oct;49(4):506-11. doi: 10.1136/gut.49.4.506.
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Mortality in patients with coeliac disease and their relatives: a cohort study.乳糜泻患者及其亲属的死亡率:一项队列研究。
Lancet. 2001 Aug 4;358(9279):356-61. doi: 10.1016/s0140-6736(01)05554-4.
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Tissue transglutaminase is the target in both rodent and primate tissues for celiac disease-specific autoantibodies.组织转谷氨酰胺酶是啮齿动物和灵长类动物组织中乳糜泻特异性自身抗体的靶标。
J Pediatr Gastroenterol Nutr. 2000 Nov;31(5):520-7. doi: 10.1097/00005176-200011000-00013.
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