Veronika Ecker, Martha-Lena Müller, Jana Wobst, Wolfgang Kern
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引用次数: 0
Abstract
CD38 and CD138 are important diagnostic markers in flow cytometric analysis of plasma cells (PC) in the context of multiple myeloma (MM). Anti-CD38 therapy, such as daratumumab, exacerbates CD38 detection. In addition, CD138 can be degraded and is then no longer easily detectable on the cell surface. Variable heavy domain heavy chain antibodies (VHH) are single variable domain antibody fragments. Clone JK36 consists of two anti-CD38 VHH fragments and allows targeting of a cryptic CD38 epitope that is not accessible to conventional antibodies (CA). Therefore, our aim was to test VHH in comparison to our conventional anti-CD38 antibody (LS198) in MM bone marrow samples after daratumumab therapy (d-t) compared to therapy-naïve (n) and samples with unknown therapy. A total of 111 samples were analyzed (n = 11 n, n = 81 d-t, n = 18 with unknown therapy). While CD38 was equally well detected by VHH and CA in therapy-naïve samples, CD38 could only be detected in 8% of d-t samples with CA but in 91% with VHH. This resulted in an overall significant reduction in the number of detectable PC, and three samples with undetectable PC by CA compared to VHH. Furthermore, CD138 was reduced/degraded in 52% of d-t samples of which 88% had undetectable CD38 by CA. In addition to proper detection of CD38, VHH is also able to determine a potential CD38 reduction of cell surface expression, as shown by a reduction in CD38 median fluorescence intensity (MFI) on d-t compared to n samples. One d-t sample revealed two distinct PC populations differing by dim and bright CD38 expression, only detectable by VHH. Interestingly, samples with unknown treatment history can be grouped into scenarios most likely treated with daratumumab, or rather treatment-naïve, respectively. In summary, VHH provides superior CD38 detection in d-t MM patients, which is vital for diagnostic samples, and it is capable of providing information about CD38 integrity on the cell surface.
期刊介绍:
Cytometry Part B: Clinical Cytometry features original research reports, in-depth reviews and special issues that directly relate to and palpably impact clinical flow, mass and image-based cytometry. These may include clinical and translational investigations important in the diagnostic, prognostic and therapeutic management of patients. Thus, we welcome research papers from various disciplines related [but not limited to] hematopathologists, hematologists, immunologists and cell biologists with clinically relevant and innovative studies investigating individual-cell analytics and/or separations. In addition to the types of papers indicated above, we also welcome Letters to the Editor, describing case reports or important medical or technical topics relevant to our readership without the length and depth of a full original report.