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@ARTICLE{Jeske:288542,
      author       = {R. Jeske$^*$ and N. Becker$^*$ and L. Kroeller$^*$ and A.
                      J. Mentzer and N. Brenner$^*$ and E. Guy and T.
                      Waterboer$^*$ and J. A. Butt$^*$},
      title        = {{A}dvancing {T}oxoplasma gondii multiplex serology.},
      journal      = {Microbiology spectrum},
      volume       = {12},
      number       = {4},
      issn         = {2165-0497},
      address      = {Birmingham, Ala.},
      publisher    = {ASM},
      reportid     = {DKFZ-2024-00406},
      pages        = {e0361823},
      year         = {2024},
      note         = {#EA:F020#LA:F020# / 2024 Apr 2;12(4):e0361823 / NEU/
                      #EA:D320#LA:D320#},
      abstract     = {Toxoplasma gondii is a highly prevalent pathogen causing
                      zoonotic infections with significant public health
                      implications. Yet, our understanding of long-term
                      consequences, associated risk factors, and the potential
                      role of co-infections is still limited. Seroepidemiological
                      studies are a valuable approach to address open questions
                      and enhance our insights into T. gondii across human
                      populations. Here, we present substantial advancements to
                      our previously developed T. gondii multiplex serology assay,
                      which is based on the immunodominant antigens SAG1 and P22.
                      While our previous bead-based assay quantified antibody
                      levels against multiple targets in a high-throughput fashion
                      requiring only a small sample volume, impaired assay
                      characteristics emerged in sample dilutions beyond 1:100 and
                      when being transferred to magnetic beads. Both are now
                      critical for inclusion in large-scale seroprevalence
                      studies. Using the truncated versions, SAG1D1 and P22trunc,
                      significantly enhanced signal-to-noise ratios were achieved
                      with almost perfect concordance with the gold-standard
                      Sabin-Feldman dye test. In sample dilutions of 1:100, the
                      diagnostic accuracy of SAG1D1 and P22trunc reached
                      sensitivities (true positive rates) of $98\%$ and $94\%$ and
                      specificities (true negative rates) of $93\%$ and $95\%,$
                      respectively. Importantly, performance metrics were
                      reproducible in a 1:1,000 sample dilution, using both
                      magnetic and nonmagnetic beads. Thresholds for
                      seropositivity were derived from finite mixture models and
                      performed equally well as thresholds by receiver operating
                      characteristic analysis. Our improved multiplex serology
                      assay is therefore able to generate robust and reproducible
                      performance metrics under various assay conditions.
                      Inclusion of T. gondii antibody measurements with other
                      pathogens, in multiplex serology panels will allow for
                      large-scale seroepidemiological
                      research.IMPORTANCEToxoplasma gondii is a pathogen of
                      significant public health concern due to its widespread
                      prevalence and zoonotic potential. However, our
                      understanding of key aspects, such as risk factors for
                      infection and disease, potential outcomes, and their trends,
                      remains limited. Seroepidemiological studies in large
                      cohorts are invaluable for addressing these questions but
                      remain scarce. Our revised multiplex serology assay equips
                      researchers with a powerful tool capable of delivering T.
                      gondii serum antibody measurements with high sensitivity and
                      specificity under diverse assay conditions. This advancement
                      paves the way for the integration of T. gondii antibody
                      measurements into multi-pathogen multiplex serology panels,
                      promising valuable insights into public health and pathogen
                      interactions.},
      keywords     = {Toxoplasma gondii (Other) / high-throughput serology
                      (Other) / multiplex serology (Other) / public health (Other)
                      / seroepidemiology (Other)},
      cin          = {F020 / D320},
      ddc          = {570},
      cid          = {I:(DE-He78)F020-20160331 / I:(DE-He78)D320-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38385741},
      doi          = {10.1128/spectrum.03618-23},
      url          = {https://inrepo02.dkfz.de/record/288542},
}