MSPrecise: A molecular diagnostic test for multiple sclerosis using next generation sequencing

• The diagnostic MSPrecise supports identification of multiple sclerosis patients.
• MSPrecise uses B cell antibody sequences from patient cerebrospinal fluid.
• MSPrecise performs well in identifying MS among a broad cohort of neurological diseases.

BackgroundWe have previously demonstrated that cerebrospinal fluid-derived B cells from early relapsing–remitting multiple sclerosis (RRMS) patients that express a VH4 gene accumulate specific replacement mutations. These mutations can be quantified as a score that identifies such patients as having or likely to convert to RRMS. Furthermore, we showed that next generation sequencing is an efficient method for obtaining the sequencing information required by this mutation scoring tool, originally developed using the less clinically viable single-cell Sanger sequencing.ObjectiveTo determine the accuracy of MSPrecise, the diagnostic test that identifies the presence of the RRMS-enriched mutation pattern from patient cerebrospinal fluid B cells.MethodsCerebrospinal fluid cell pellets were obtained from RRMS and other neurological disease (OND) patient cohorts. VH4 gene segments were amplified, sequenced by next generation sequencing and analyzed for mutation score.ResultsThe diagnostic test showed a sensitivity of 75% on the RRMS cohort and a specificity of 88% on the OND cohort. The accuracy of the test in identifying RRMS patients or patients that will develop RRMS is 84%.ConclusionMSPrecise exhibits good performance in identifying patients with RRMS irrespective of time with RRMS.