Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA.
Department of Nephrology, Akron Children's Hospital, Akron, OH, USA.
Pediatr Nephrol. 2022 Jul;37(7):1479-1493. doi: 10.1007/s00467-022-05451-2. Epub 2022 Feb 3.
Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, D-dimer, as well as anti-CFH antibodies.
An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported.
The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75-175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30-75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2-42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14-40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6-43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4-18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6-26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186-569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and D-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range.
If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and D-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information.
观察影响替代途径失调成分的生物标志物，可能有助于获得一种新的、更快速的非典型溶血尿毒综合征诊断方法。我们对 aHUS 生物标志物进行了系统评价：C3、C5a、C5b-9、因子 B、补体因子 B、H 和 I、CH50、AH50、D-二聚体以及抗 CFH 抗体。
对 aHUS 患者的血浆/血清进行了全面的文献检索，这些样本是在诊断时采集/报告的。共纳入 60 项研究，涉及 837 例 aHUS 患者，至少报告了一种生物标志物。
生物标志物 C3 [平均值 (SD)：72.1 (35.0)，中位数：70.5 与参考范围：75-175mg/dl，n=752]；CH50 [28.3 (32.1)，24.3 与参考范围：30-75U/ml，n=63]；AH50 [27.6% (30.2%)，10%与参考范围：≥46%，n=23]；和 CFB [13.1 (6.6)，12.4 与参考范围：15.2-42.3mg/dl，n=19]在 aHUS 患者中低于参考范围。生物标志物包括 C4 [平均值 (SD)：20.4 (9.5)，中位数：20.5 与参考范围：14-40mg/dl，n=343]；C4d [7.2 (6.5)，4.8 与参考范围：≤9.8μg/ml，n=108]；CFH [40.2 (132.3)，24.5 与参考范围：23.6-43.1mg/dl，n=123 名患者]；和 CFI [8.05 (5.01)，6.55mg/dl 与参考范围：4.4-18.1mg/dl，n=38]在 aHUS 患者中均在参考范围内。生物标志物 C5a [平均值 (SD)：54.9 (32.9)，中位数：48.8 与参考范围：10.6-26.3mg/dl，n=117]；C5b-9 [466.0 (401.4)，317 (186-569.7)与参考范围：≤250ng/ml，n=174]；Bb [2.6 (2.1)，1.9 与参考范围：≤1.6μg/ml，n=77]和 D-二聚体 [246 (65.05)，246 与参考范围：<2.2ng/ml，n=2 名患者]在 aHUS 患者中高于参考范围。
如果根据我们的数据构建一个全面的补体谱，那么 C3、CH50、AH50 和 CFB 水平降低，C5a、C5b-9、Bb、抗 CFH 自身抗体和 D-二聚体水平升高，就可以识别出 aHUS。补充材料中提供了一个更高分辨率的图表概要。
