Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis

Tanuja Chitnis; John Foley; Carolina Ionete; Nabil K El Ayoubi; Shrishti Saxena; Patricia Gaitan-Walsh; Hrishikesh Lokhande; Anu Paul; Fermisk Saleh; Howard Weiner; Ferhan Qureshi; Michael J Becich; Fatima Rubio da Costa; Victor M Gehman; Fujun Zhang; Anisha Keshavan; Kian Jalaleddini; Ati Ghoreyshi; Samia J Khoury

doi:10.1016/j.clim.2023.109688

Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis

Clin Immunol. 2023 Aug:253:109688. doi: 10.1016/j.clim.2023.109688. Epub 2023 Jul 4.

Authors

Tanuja Chitnis¹, John Foley², Carolina Ionete³, Nabil K El Ayoubi⁴, Shrishti Saxena⁵, Patricia Gaitan-Walsh⁶, Hrishikesh Lokhande⁷, Anu Paul⁸, Fermisk Saleh⁹, Howard Weiner¹⁰, Ferhan Qureshi¹¹, Michael J Becich¹², Fatima Rubio da Costa¹³, Victor M Gehman¹⁴, Fujun Zhang¹⁵, Anisha Keshavan¹⁶, Kian Jalaleddini¹⁷, Ati Ghoreyshi¹⁸, Samia J Khoury¹⁹

Affiliations

¹ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: tchitnis@rics.bwh.harvard.edu.
² Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, UT, USA. Electronic address: ldjfoley@gmail.com.
³ University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: carolina.ionete@umassmemorial.org.
⁴ Nehme and Thgerese Tohme Multiple Sclerosis Center, American University of Beirut, Beirut, Lebanon. Electronic address: ne42@aub.edu.lb.
⁵ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ssaxena3@bwh.harvard.edu.
⁶ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: pgaitanwalsh@bwh.harvard.edu.
⁷ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: hlokhande@bwh.harvard.edu.
⁸ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: apaul12@bwh.harvard.edu.
⁹ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: fermisk.x@gmail.com.
¹⁰ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: hweiner@rics.bwh.harvard.edu.
¹¹ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: fqureshi@octavebio.com.
¹² Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: mjbecich@gmail.com.
¹³ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: fatima.rubio@gmail.com.
¹⁴ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: vmgehman@gmail.com.
¹⁵ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: fujun2@yahoo.com.
¹⁶ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: akeshavan@octavebio.com.
¹⁷ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: kianj@octavebio.com.
¹⁸ Octave Bioscience, Inc., Menlo Park, CA, USA. Electronic address: aghoreyshi@octavebio.com.
¹⁹ Nehme and Thgerese Tohme Multiple Sclerosis Center, American University of Beirut, Beirut, Lebanon. Electronic address: sk88@aub.edu.lb.

PMID: 37414379
DOI: 10.1016/j.clim.2023.109688

Abstract

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.

Keywords: Clinical validation; Gadolinium-positive lesion; MS disease activity; Multiple sclerosis.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Blood Proteins
Gadolinium
Humans
Magnetic Resonance Imaging
Multiple Sclerosis*

Substances

Blood Proteins
Gadolinium