張 文 王懷連
【摘要】 糖抗原(carbohydrate antigen, CA) 19-9是一種同結(jié)直腸癌細胞株免疫小鼠所獲抗體結(jié)合的抗原。腫瘤標志物(tumor marker)是反映腫瘤存在的化學(xué)類物質(zhì)。它們不存在于正常成人組織而僅見于胚胎組織,或在腫瘤組織中的含量大大超過在正常組織里的含量,它們的存在或量變可以提示腫瘤的性質(zhì),借以了解腫瘤的組織發(fā)生、細胞分化、細胞功能,以幫助腫瘤的診斷、分類、預(yù)后判斷以及治療指導(dǎo)。在胰腺癌,膽囊癌,膽管癌患者血清中CA19-9顯著升高,因此在臨床上作為膽胰系統(tǒng)腫瘤的標志物被廣為使用。但是亦有因服用胃黏膜保護劑或膽胰炎性反應(yīng)等導(dǎo)致CA19-9假陽性的報道。本文1例與臨床表現(xiàn)嚴重不符的血清CA19-9升高的病例,在此做一報道,并對假陽性的原因作了分析。
【關(guān)鍵詞】 CA19-9;異常升高
Inconsistent with the clinical manifestations of abnormal increase of seram CA19-9 and cause analysis 1 case
ZHANG Wen,WANG Huai-lian.Dalian City Maternity Hospital,Liaoning 116021,China
【Abstract】 Objective Carbohydrate antigen (CA) 19-9 is a kind of antigen which link to antibody aquired by mouse immunized with colon and rectal cancer cell strains. Tumor marker is a kind of chemical matter reflect tumor existence. They don't exist normal adult tissue but embryonal tissue either, or their contents in tumor tissue exceed nomal tissue extremely. Their exsistence or quantitative change maybe present tumor quality to realize occurrence of tumor tissue, cells differentiation, and cells function, which can help the diagnosis , classification, prognosis and therapic instruction of tumor. Level of CA19-9 rises in patients' serum of pancreatic cancer, gallbladder cancer and cholangiocarcinoma, so it is used widely as marker of pancreatic and gallbladder system clinically. Nevertheless, it was reported that taking mucosal protective agent or pancreatic and gallbladder inflammation and so on could induce false positive of CA19-9. The author find out a case of CA19-9 levels rise which does't accord with clinical represention extremely, report as follows and analyse the reason of false positive.
【Key words】 CA19-9;Rise abnormally
1 臨床資料
患者女,52歲,丙型肝炎病毒陽性,因血清中CA19-9異常升高而被疑為胰腺癌。其他腫瘤標志物檢測值均在正常范圍,腹部超聲,CT等影像學(xué)檢查均未見明顯腫瘤。
2 CA19-9的檢測
采用化學(xué)發(fā)光酶免疫測定法(chemiluminescent enzyme immunoassay, CLEIA),固相為鼠抗人CA19-9抗體結(jié)合微粒,標記抗體為堿性磷酸酶標記的鼠抗人CA19-9抗體。正常值在37IU/ml以下。
3 假陽性原因的解析
稀釋線性的探討,倍比稀釋后檢測值如表1所示。稀釋后測定值明顯呈非線性分布,因此筆者懷疑這可能是由于患者體內(nèi)存在嗜異種抗體(heterophile antibody, hAb)所導(dǎo)致的非特異性反應(yīng)所致,因此筆者加入PEG(polythylene glycol)處理后,對離心所獲上清(不含抗體成分)和沉淀分別進行CA19-9的測定,結(jié)果如表2。上清稀釋后測定值呈線性分布,我們推斷該患者實際CA19-9值為4~5IU/ml。而含抗體的沉淀部分稀釋后測定值依然不呈線性分布。
4 討論
近年,免疫測定法廣泛應(yīng)用于腫瘤標志物等體內(nèi)微量物質(zhì)的測定中,CA19-9升高見于 大部分胰腺癌患者血清CA19-9水平明顯增高肝膽系癌、胃癌、結(jié)直腸癌的CA19-9水平也會升高,低濃度增高、一過性增高可見于慢性胰腺炎、膽石癥、肝硬化、腎功能不全、糖尿病等。但是有一部分患者血清中存在的嗜異種抗體可以直接與檢測抗體或固相支持物結(jié)合,導(dǎo)致非特異反應(yīng)[1],人抗鼠抗體就是其中之一。本文病例,可能就是患者體內(nèi)的人抗鼠抗體直接與固相支持物或標記抗體結(jié)合,導(dǎo)致CA19-9假性升高。在日常工作中,如果存在嗜異種抗體稀釋后的測定值會偏離線性分布,而且PEG處理可以明確嗜異種抗體的存在。因此需時刻銘記免疫測定時可能引起非特異反應(yīng),對測定的原理,使用試劑的特性有充分的理解十分必要。
參考文獻
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[2] 閆慧.腫瘤標志物CEA CA19-9,CA242 Ferritin對胰腺癌診斷的意義. 長治醫(yī)學(xué)院院報,2005,4.
[3] Boscato LM, Stuart MC. Incidence and specificity of interference in two-site immunoassays. Clin Chem, 1986,32:1491-1495.