Abstract
Despite the availability of advances in molecular diagnostic testing for infectious disease, there is still a need for tools that advance clinical care and public health. Current methods focus on pathogen detection with unprecedented precision, but often lack specificity. In contrast, the host immune response is highly specific for the infecting pathogen. Serological studies are rarely helpful in clinical settings, as they require acute and convalescent antibody testing. However, the B cell response is much more rapid and short-lived, making it an optimal target for determining disease aetiology in patients with infections. The performance of tests that aim to detect circulating antigen-specific antibody-secreting cells (ASCs) has previously been unclear. Test performance is reliant on detecting the presence of ASCs in the peripheral blood. As such, the kinetics of the ASC response to infection, the antigen specificity of the ASC response, and the methods of ASC detection are all critical. In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent following day 14 since onset of symptoms. Data show a sensitivity of ~90% and specificity >80% for pathogen detection using ASC-based methods. Overall, the summarised work indicates that ASC-based methods may be very sensitive and highly specific for determining the etiology of infection and have some advantages over current methods. Important areas of research remain, including more accurate definition of the timing of the ASC response to infection, the biological mechanisms underlying variability in its magnitude and the evolution and the B cell receptor in response to immune challenge. Nonetheless, there is potential of the ASC response to infection to be exploited as the basis for novel diagnostic tests to inform clinical care and public health priorities.
Highlights
The production of pathogen-specific antibody by B lymphocytes (B cells) is of key importance for protection from infection
We searched MEDLINE with combinations of the following terms “B cell,” “plasmablast,” “plasma cell,” “antibody-secreting cell” AND “infection” AND “kinetics,” “dynamics.” We identified peer-reviewed articles of interest, and conducted further searches for terms identified as important (e.g. “antibodies lymphocyte supernatant,” “enzyme-linked immunospot assay (ELISpot),” “B cell receptor sequencing” in the context of infection)
Here we describe the detection of antigen-specific antibodysecreting cells (ASCs) by the use of ELISpot and assay of antibody from lymphocyte supernatant (ALS) (Table 1), ELISpot has been used for the immunophenotyping of B cell subsets for a variety of non-immunoglobulin markers [14]
Summary
The production of pathogen-specific antibody by B lymphocytes (B cells) is of key importance for protection from infection. Patient blood samples at 7 days following onset of symptoms ELISpot to detect whole cell, P fimbria or OmpA-specific IgM/A/G ASCs 46 adult patients with severe dengue infection Patient blood samples on day of admission (median 6, range 2–8, days following onset of fever) and convalescence ELISpot to detect dengue-virus-specific IgM/A/G ASCs (using purified dengue virions)
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