Development of an Automated Complement C5 Functional Assay for Personalized Monitoring of Patients on C5 Inhibitors
نویسندگان
چکیده
Abstract Background Humanized anti-C5 monoclonal antibody therapeutics has been heralded as a breakthrough treatment for Paroxysmal Nocturnal Hemoglobinuria and atypical Hemolytic Uremic Syndrome. Therapeutic drug monitoring is currently not widely available but assessing complement blockage maybe useful to monitor optimize Eculizumab or Ravlizumab efficacy. Recent studies have suggested using C5 functional assays specific target assess blockage. The aim of this study was the analytical performance an automated assay we developed by modifying CH50 used in our laboratory. Methods Patient sera mixed different ratios (20-90%) with commercially C5-deficient (C5d) serum (Quidel corp. SD) were tested lytic activity liposome (Optilite, Binding site, Birmingham, UK). Normal lysis ensures intact exclusively from patient serum. A ratio that led normal healthy defective factors other than considered optimal. This adopted preliminary reference intervals (n=34 donors) bi-weight quantile method estimation at 90% confidence interval. Accuracy assessed recovery studies. Specimens (n=2) created varying levels (Biovision, CA). Recovery calculated (measured/expected) adding back 100 ug/mL purified comparing values original results. To evaluate specificity, specimens (n=22) components (C2, C3, C4) C5d measured. Results 75% 25% establish interval 32.3 – 46.7 U/mL. two accuracy samples had initial 37.9 41.7 U/mL 14.2 20.6 after depletion, respectively. Adding Eculizumab-depleted yielded 36.5 39.9 recoveries 96%. non-C5 complement-deficient specificity low ranging 11.8 28.8 After mixing C5d, 21/22 demonstrated low-normal (range: 28.4 -41.6 U/mL). Conclusion optimal maintaining recovering deficiencies C5. C5-depleted did regain these regained activity, confirming non-functional inhibitor interfering assay. Specimens’ recovered when 95.5% specimens, These data demonstrate acceptable developed.
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ژورنال
عنوان ژورنال: American Journal of Clinical Pathology
سال: 2022
ISSN: ['0002-9173', '1943-7722']
DOI: https://doi.org/10.1093/ajcp/aqac126.019