The impact of eculizumab on routine complement assays.

Autor: Willrich MAV; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: willrich.mariaalice@mayo.edu., Andreguetto BD; Department of Clinical Pathology, University of Campinas, Campinas, Sao Paulo, Brazil., Sridharan M; Division of Hematology, Mayo Clinic, Rochester, MN, USA., Fervenza FC; Division of Nephrology, Mayo Clinic, Rochester, MN, USA., Tostrud LJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Ladwig PM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Rivard AM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Hetrick MD; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Olson RN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Bryant SC; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Snyder MR; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Murray DL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: murray.david@mayo.edu.
Jazyk: angličtina
Zdroj: Journal of immunological methods [J Immunol Methods] 2018 Sep; Vol. 460, pp. 63-71. Date of Electronic Publication: 2018 Jun 20.
DOI: 10.1016/j.jim.2018.06.010
Abstrakt: Background: Eculizumab (ECU) blocks complement C5 cleavage, preventing the formation of C5a and the cytolytic effects of the membrane attack complex. The presence of ECU in blood impacts routine complement tests used to monitor treatment.
Methods: Residual serum samples with normal total complement (CH50) and residual citrate plasma with normal PT/APTT were spiked with ECU at varied concentrations ranging from 25 to 600 μg/mL. In addition, seventy-one samples from patients on ECU were obtained. Artificial and patient samples were analyzed for CH50 and C5 function (Wako Diagnostics), C5 concentration (Quidel), AH50 (Wieslab ELISA) and sMAC (Quidel). ECU concentration was measured by mass spectrometry for all patients.
Results: Complement blockage by ECU was evident in spiked artificial samples. At 25 μg/mL ECU, partial complement blockage was observed in CH50, AH50 and C5 function in serum. Complete blockage defined by undetectable AH50 (<10%) occurred at 100 μg/mL ECU. C5 concentrations remained the same regardless of ECU. sMAC results stayed around 81% of baseline in serum and 47% in citrate plasma with 50μg/mL ECU. Patient samples had ECU ranging from <5 to 1220 μg/mL. In all patients with ECU >100 μg/mL, C5 function was <29 U/mL.
Conclusions: The spiked sera and patient samples showed complement blockage with CH50, AH50 and C5 function assays when ECU >100 μg/mL. CH50, AH50 or C5 function assays can serve as indicators for the pharmacodynamic effects of eculizumab. Allied to ECU concentration, laboratory studies may be helpful to tailor therapy.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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