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内镜下输尿管下胶原蛋白注射:免疫学方面的担忧合理吗?

Endoscopic subureteral collagen injection: are immunological concerns justified?

作者信息

Leonard M P, Decter A, Hills K, Mix L W

机构信息

Department of Pediatric Urology, University of Manitoba, Winnipeg, Canada.

出版信息

J Urol. 1998 Sep;160(3 Pt 2):1012-6.

PMID:9719266
Abstract

PURPOSE

We evaluated the humoral immune response in children treated with subureteral collagen injection for vesicoureteral reflux by analyzing serum for anticollagen antibodies.

MATERIALS AND METHODS

We obtained serum before skin testing and at intervals after subureteral collagen injection in 7 girls and 3 boys with a mean age plus or minus standard error of 9.2+/-1.4 years. Serum antibody titers to bovine collagen, and human collagen types I and III were determined by indirect enzyme-linked immunosorbent assay. Patients were assessed for adverse reactions related to an immune response to collagen.

RESULTS

Followup ranged from 14 to 40 months (mean 24.6) after the initial subureteral collagen injection. One to 4 subureteral collagen injections were given with cumulative collagen volume per patient ranging from 0.15 to 5.1 cc (mean 2.1). In 2 cases no baseline serum sample was obtained. Antibody titers measured in the 8 other patients before skin testing revealed equivocal and negative results in 5 and 3 for antibovine collagen, and in 1 and 7 for antihuman collagen types I and III, respectively. At the last followup results were positive, equivocal and negative in 3, 5 and 2 for antibovine collagen, and in 0, 2 and 8 for antihuman collagen types I and III, respectively. Seroconversion developed 13 to 24 months after the initial subureteral collagen injection in antibovine collagen seropositive patients, including 1 with a limited episode of bladder irritability after seroconversion. No other patient had adverse events considered to be immunological.

CONCLUSIONS

In 3 of the 10 children treated with subureteral collagen injection for vesicoureteral reflux serum antibodies to bovine collagen developed. The volume of collagen injected was small, suggesting that volume is not a major determinant of immunogenicity. In 1 patient with seroconversion a local reaction may have been immunogenic. No patient had systemic symptoms of autoimmune disease and there was no seroconversion to antibodies cross-reacting with human collagen.

摘要

目的

通过分析血清中的抗胶原蛋白抗体,评估接受输尿管下胶原蛋白注射治疗膀胱输尿管反流的儿童的体液免疫反应。

材料与方法

我们在7名女孩和3名男孩中获取了皮肤试验前以及输尿管下胶原蛋白注射后不同时间点的血清,这些患儿的平均年龄为9.2±1.4岁(平均年龄±标准误差)。通过间接酶联免疫吸附测定法测定血清中针对牛胶原蛋白以及人I型和III型胶原蛋白的抗体滴度。评估患者与胶原蛋白免疫反应相关的不良反应。

结果

初次输尿管下胶原蛋白注射后的随访时间为14至40个月(平均24.6个月)。每位患者接受了1至4次输尿管下胶原蛋白注射,每位患者的累积胶原蛋白量为0.15至5.1立方厘米(平均2.1立方厘米)。2例患者未获取基线血清样本。在其他8名患者中,皮肤试验前测得的抗牛胶原蛋白抗体滴度结果为5例可疑和3例阴性,抗人I型和III型胶原蛋白抗体滴度结果分别为1例可疑和7例阴性。在最后一次随访时,抗牛胶原蛋白抗体滴度结果为3例阳性、5例可疑和2例阴性,抗人I型和III型胶原蛋白抗体滴度结果分别为0例阳性、2例可疑和8例阴性。抗牛胶原蛋白血清阳性患者在初次输尿管下胶原蛋白注射后13至24个月出现血清转化,其中1例在血清转化后出现了短暂的膀胱刺激症状。没有其他患者出现被认为与免疫相关的不良事件。

结论

在接受输尿管下胶原蛋白注射治疗膀胱输尿管反流的10名儿童中,有3名儿童产生了针对牛胶原蛋白的血清抗体。注射的胶原蛋白量较少,表明注射量不是免疫原性的主要决定因素。在1例发生血清转化的患者中,局部反应可能具有免疫原性。没有患者出现自身免疫性疾病的全身症状,也没有出现与人类胶原蛋白交叉反应抗体的血清转化。

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