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

ABSTRACT Introduction Free light chain kappa (FLCκ) 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 FLCκ analysis simplifying cerebrospinal fluid (CSF) analysis. Methods The 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 FLCκ or Ig synthesis to represent real world data. Primary outcome parameter is the sensitivity and negative predictive value of the absence of local FLCκ synthesis for the absence of intrathecal synthesis according to OCB and/or intrathecal IgG, IgA, IgM synthesis in quotient diagrams. The reference range of FLCκ will be indicated by the FLCκ quotient diagram. This study was designed according to the STARD criteria. Perspective The 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 FLCκ 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.