恶性血液病患者侵袭性真菌感染GM和BG抗原检测的价值

The significance of serum GM and BG antigens assay for invasive fungal infections in hematological malignancies patients

目的 评价半乳甘露聚糖（GM）抗原和（1→3）-β-D葡聚糖（BG）抗原检测对恶性血液病患者侵袭性真菌感染（IFI）的诊断价值以及两种方法在监测抗真菌治疗效果中的作用.方法 51例恶性血液病患者当体温超过38 ℃,持续48 h以上,经广谱抗生素治疗无效,或起初有效但体温下降后再次升高时被纳入本研究.第1周采集患者静脉血2次,以后每周采血1次,至少监测4周.分别采用ELISA法和比色法检测患者血清GM和BG值.GM实验阳性定义为连续两次不同时点检测GM值＞0.5或单次＞0.8,G实验阳性定义为BG值＞80 pg/ml.患者分为确诊、临床诊断、拟诊及非真菌感染四组,21名正常志愿者作为对照.结果 51例患者共收集240份血清标本.其中确诊IFI2例,临床诊断26例,拟诊17例,非真菌感染6例.以确诊及临床诊断为真阳性组,以非真菌感染为真阴性组.GM实验在真阳性组28例中21例阳性,真阴性组6例中1例阳性,敏感性75%,特异性83.3%,阳性预测值95.5%,阴性预测值41.7%;G实验在真阳性组28例中全部阳性,真阴性组6例中4例阳性,敏感性100%,特异性33.3%,阳性预测值87.5%,阴性预测值100%.G实验的敏感性高于GM实验,差异有统计学意义（P=0.015）;但特异性差异无统计学意义（P=0.242）.GM实验阳性的21例患者中抗真菌治疗有效19例,GM值渐转阴性,2例无效的患者GM值持续阳性,有效组GM平均值两周后明显低于无效组,差异有统计学意义（P＜0.05）;G实验阳性的患者中治疗有效者BG值逐渐下降,但未转阴;治疗无效组BG值变化无规律,总体呈上升趋势,但各时间点BG值监测对疗效无明显判断意义.结论 血清GM和BG抗原检测可以为早期诊断IFI提供有力证据,联合检测BG和GM两种抗原,可提高对曲霉菌诊断的特异性,减少假阳性.治疗中监测GM和BG值的动态变化,GM实验用于评价疗效的价值优于G实验.

Objective To evaluate the diagnostic value of serum galactomannan antigen （GM）and （1→3）-β-D-glucan antigen（BG） assay in invasive fungal infections（ IFI ） in the patients with hematologic malignancies and the role in monitoring therapeutic response. Methods Fifty one patients with hematological malignancies met the criteria for inclusion： ①body temperature above 38 ℃ for 48 hours, ②failure to respond to broad-spectrum antibiotic treatment, or ③temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay（ EL1SA ）and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value 〉 0.5 or 〉 0. 8 and the positive G test is defined as BG value 〉 80 pg/ml. The patients were assigned into four groups as proven,probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls. Results Two hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity,positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test （ P = 0.015 ）, but there was no significant difference in specificity of the two tests （P =0.242）. In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group （P 〈 0.05 ）. BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness. Conclusions Serum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.