Prospective multicenter validation of a new laboratory workflow integrating the free light chains kappa quotient in CSF analysis-Protocol of the ORCAS study

IntroductionFree light chain kappa (FLC{kappa}) are a newer sensitive biomarker to detect intrathecal immunoglobulin synthesis. Here we report the study protocol of the ORCAS study which will evaluate a novel laboratory work flow recently proposed including FLC{kappa} analysis simplifying cerebrospinal fluid (CSF) analysis. MethodsThe ORCAS study is a prospective multicenter diagnostic biomarker study across at least 4 study sites. The study protocol does not specify which assays should be applied in the participating laboratories to detect oligoclonal bands (OCB) or measure FLC{kappa} or Ig synthesis to represent real world data. Primary outcome parameter is the sensitivity and negative predictive value of the absence of local FLC{kappa} synthesis for the absence of intrathecal synthesis according to OCB and/or intrathecal IgG, IgA, IgM synthesis in quotient diagrams. The reference range of FLC{kappa} will be indicated by the FLC{kappa} quotient diagram. This study was designed according to the STARD criteria. PerspectiveThe establishment of a newer biomarker in routine practice is associated with significant difficulties, such as the inconsistent comparability of different measurement platforms, the establishment of suitable cut-offs or insufficient knowledge regarding sensitivity and specificity of the biomarker. If the ORCAS study objective is achieved, the use of the proposed workflow integrating FLC{kappa} analysis in routine practice in CSF diagnostics could help to better characterize the intraindividual and disease-specific intrathecal humoral immune response in a resource-efficient manner.