尿BK病毒载量与干细胞移植后出血性膀胱炎的关系

The BK virus load in urine in association with the development of hemorrhagic cystitis after hematopoietic stem cell transplantation

目的分析BK病毒尿与造血干细胞移植（HSCT）术后迟发性出血性膀胱炎（LOHC）的相关性，探讨BK病毒载量与LOHC发病的关系。方法收集2006年8月至2008年4月113例HSCT患者的晨尿标本，提取病毒DNA，用PCR方法扩增多瘤病毒DNA，以40名健康成人为对照。用实时定量PCR方法检测尿BK病毒阳性患者在LOHC不同时期的尿标本中BK病毒DNA拷贝数。结果113例HSCT患者中22例（19．5％）发生HC，中位发生时间为＋44（＋13～＋114）d，包括1级7例，2级11例，3级3例，4级1例。其中21例（95．5％）LOHC患者尿标本经PCR检出BK病毒，检出率明显高于非LOHC组（31．9％）（P=0．000）。健康对照组均未检出BK病毒。定量PCR检测结果显示，LOHC患者尿BK病毒DNA拷贝数在HC发病前1周的平均水平较初次阳性时有明显上升（10^3拷贝数／μl比10^4拷贝数／μl），在HC发病当周及缓解后1周无明显改变。不同级别LOHC患者在发病前和发病时尿BK病毒DNA拷贝数差异无统计学意义。非LOHC患者尿中BK病毒DNA拷贝数平均水平为10^3～10^4拷贝数／μl，低于LOHC患者。结论BK病毒尿是HSCT后LOHC的重要致病原因。如HSCT患者尿中BK病毒DNA拷贝数呈动态上升并超过10^5拷贝数／μl时可能预示LOHC的发生。

Objective To analyze the relationship between BK viruria and the late onset hemorrhagic cystitis （LOHC） after hematopoietie stem cell transplantation （HSCT）, and investigate the role of BK virus load in the development of LOHC. Methods From August 2006 to April 2008, urine samples were collected weekly from 113 patients undergoing HSCT. Virus DNA were extracted from the urine samples and amplified by qualitative PCR. Real-time quantitative PCR was used to quantify BKV DNA in the urine samples of all BK viruria patients. Results LOHC occurred in 22 patients （ 19.5% ） , including grade 1 in 7, grade 2 in 11, grade 3 in 3, and grade 4 in one. The median onset time was 44 （ 13 - 114 ） days after transplantation. Twenty-one of which （95.5%） were BK virus positive, being sigificantly higher than that in non-LOHC patients （31.9%） （P = 0. 000）. No BK virus was detected in the healthy control group at the same time. Quantitative PCR detection showed that the mean BK virus DNA copies in LOHC patients at a week before occurring HC was higher than that at the first positive samples （ 105 eopies/μl versus 104 copies/μl, P = 0. 025 ）, and it was no significant change at the onset and a week after HC. Meanwhile, there was no statistical difference in the mean level of BK virus DNA copies among the LOHC patients with different grades. The mean level of BK virus DNA copies in non-HC patients was 103 to 104 copies/μl, being lower than that in LOHC patients. Conclusions BK viruria is an important pathogenic cause of the LOHC after HSCT. The occurrence of BKV viruria in HSCT patients, together with the increasing of BK virus DNA copies in urine, over the level of 105 copies/μl may indicate a possible development of LOHC.