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

作者：Rounds William H; Salinas Edward A; Wilks Tom B II; Levin Mikhail K; Ligocki Ann J; Ionete Carolina; Pardo Carlos A; Vernino Steven; Greenberg Benjamin M; Bigwood Douglas W; Eastman Eric M; Cowell Lindsay G; Monson Nancy L^*

来源：Gene, 2015, 572(2): 191-197.

DOI：10.1016/j.gene.2015.07.011

• Multiple sclerosis
• Neurological disease
• Biomarker
• B cell
• Genetics
• High-throughput nucleotide sequencing

Background: We 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.
Objective: To determine the accuracy of MSPrecise, the diagnostic test that identifies the presence of the RRMS-enriched mutation pattern from patient cerebrospinal fluid B cells.
Methods: Cerebrospinal 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.
Results: The 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%.
Conclusion: MSPrecise exhibits good performance in identifying patients with RRMS irrespective of time with RRMS.

• 出版日期2015-11-10