A-141 Biological variation of soluble B-cell maturation antigen in healthy donors

Background B-cell maturation antigen (BCMA) is a receptor involved in the development and function of B-cells, primarily expressed on plasma cells and some mature B-cells. The soluble form of BCMA (sBCMA) is detectable in peripheral blood following cleavage from the cell membrane. Elevated levels of sBCMA have been associated with haematological malignancies, particularly multiple myeloma, and other B-cell disorders. However, the clinical utility of sBCMA measurements is contingent upon a comprehensive understanding of its biological variation (BV). The aim of our study was to establish the within- and between-subject BV of sBCMA in healthy donors in compliance with European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) guidance. Methods Serum samples were collected from 29 healthy donors (14 females, 15 males, age range 23 – 62 years) over the course of 10 weeks across 2 locations in Birmingham, UK. One donor finished only 6 collections. Each participant was bled within the same 3-hour window each week. Blood was processed by the same operator to minimise sample handling variation and samples were stored at -80°C until testing. Testing was also performed by the same operator and all samples from the same donor were tested at the same time to minimise analytical variation. The sBCMA was measured in duplicates using a novel ELISA kit currently in development by The Binding Site (part of Thermo Fisher Scientific). Outlier and homogeneity analysis were performed using Tukey’s Fences test and Brown-Forsythe test, respectively. Sample variation was assessed to confirm samples were in steady-state. The distribution of data was measured using Kolmogorov-Smirov test. The within-subject variation (CVI), between-subject variation (CVG) and analytical CV (CVA) were calculated using ANOVA test. Results Statistical analysis was performed on the full data set as no outliers were identified. Levels of sBCMA in the samples were confirmed to be in steady-state. The data also satisfied criteria for both normality and variance homogeneity. The mean sBCMA leveand females. ANOVA analysis determined the CVI to be 8.9% [CI 95% 8.1-9.8] and the CVG as 22.75% [CI 95% 17.9–31.1]. In male participants the CVI was 8.1% (CI 95% 6.8-9.7) and the CVG was 19.3% (CI 95% 13.9-30.6). In female participants the CVI was 9.7% (CI 95% 8.9-11.4) and the was CVG 27% (CI 95% 19.2-44). CVA for the study was determined to be 5.60% [CI 95% 4.9–6.2] which was used with the CVI to calculate a reference change value (RCV) of 29.1%. Total allowable error (TEa), calculated from the root sum of squares, was 49.1%. l in our cohort was 6.60 ng/mL. There was no significant difference in mean concentration of sBCMA between males Conclusion To our knowledge, this is the first study to determine the BV for sBCMA in healthy subjects. Quality BV data is crucial for potential clinical application such as improved assessment of multiple myeloma disease progression and monitoring of ongoing therapy.