粒细胞巨噬细胞集落刺激因子作为慢性肾衰竭患者乙肝疫苗接种佐剂的疗效——一项前瞻性随机试验的结果

Efficacy of GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure--results of a prospective, randomized trial.

作者信息

Singh N P, Mandal S K, Thakur A, Kapoor D, Anuradha S, Prakash A, Kohli R, Agarwal S K

机构信息

Nephrology Division, Department of Medicine, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India.

出版信息

Ren Fail. 2003 Mar;25(2):255-66. doi: 10.1081/jdi-120018726.

DOI:10.1081/jdi-120018726

PMID:12739832

Abstract

BACKGROUND

Chronic renal failure patients on hemodialysis are at an increased risk of acquiring hepatitis B infection. Hence vaccination against hepatitis B assumes great importance in these patients. However, the response to hepatitis B vaccination is poor, even when 4 double doses (40 microg) of the vaccine are given. This study was conducted to determine the efficacy of GM-CSF as an adjuvant to hepatitis B vaccine in CRF patients.

METHODS

CRF patients including both hemodialysis (HD) and non-dialysis (ND) patients were randomized to receive either placebo or a single injection of GM-CSF (in varying doses of 50 microg, 100 microg, 150 microg) a day prior to the 1st dose of recombinant hepatitis B vaccine (40 microg). Three more doses of the vaccine were given at 1, 2, and 6 months. The anti-HBs antibody titres were measured by ELISA at 3 and 7 months. Patients having antibody titres less than 10 IU/L were considered non-responders. The response rate and mean antibody titers were compared between the control (I) and GM-CSF (II) groups.

RESULTS

In group I, 31 and 27 patients were available for evaluation at 3 and 7 months respectively. In group II, 33 and 28 patients could be evaluated at the same time points. Within the control group (group I), the response rate in hemodialysis patients (63.6%) was lower as compared to non-dialysis patients (81.2%). The response rate in group II was higher than that in group I at both 3 months as well as 7 months (78.1% vs. 62.3% and 89.3% vs. 74.1%, p = ns). The best response rates in group II were observed when GM-CSF was used in a dose of 150 microg (90.9% at 3 months and 100% at 7 months). The mean antibody titers were also found to be higher in the group II as compared to group I (409.6 vs. 243.9 IU/L, p = 0.01).

CONCLUSION

The results of this randomized, prospective study suggest that: 1. Patients with chronic renal failure should be vaccinated for hepatitis B as chronic renal insufficiency is established. 2. GM-CSF is an effective adjuvant to hepatitis B vaccine in these patients especially when a priming dose of 150 microg is used prior to 1st dose of hepatitis B vaccination.

摘要

背景

接受血液透析的慢性肾衰竭患者感染乙型肝炎的风险增加。因此，对这些患者进行乙型肝炎疫苗接种非常重要。然而，即使给予4剂双倍剂量（40微克）的疫苗，对乙型肝炎疫苗的反应仍较差。本研究旨在确定粒细胞巨噬细胞集落刺激因子（GM-CSF）作为乙型肝炎疫苗佐剂在慢性肾衰竭患者中的疗效。

方法

将包括血液透析（HD）和非透析（ND）患者在内的慢性肾衰竭患者随机分组，在第1剂重组乙型肝炎疫苗（40微克）前1天接受安慰剂或单次注射不同剂量（50微克、100微克、150微克）的GM-CSF。在1、2和6个月时再接种3剂疫苗。在3个月和7个月时通过酶联免疫吸附测定（ELISA）测量抗-HBs抗体滴度。抗体滴度低于10 IU/L的患者被视为无反应者。比较对照组（I）和GM-CSF组（II）的反应率和平均抗体滴度。

结果

在I组中，分别有31例和27例患者在3个月和7个月时可供评估。在II组中，在相同时间点有33例和28例患者可进行评估。在对照组（I组）中，血液透析患者的反应率（63.6%）低于非透析患者（81.2%）。II组在3个月和7个月时的反应率均高于I组（78.1%对62.3%以及89.3%对74.1%，p =无统计学意义）。当使用150微克剂量的GM-CSF时，II组的反应率最佳（3个月时为90.9%，7个月时为100%）。还发现II组的平均抗体滴度高于I组（409.6对243.9 IU/L，p = 0.01）。