PT - JOURNAL ARTICLE AU - Sabine Tacke AU - Stefan Braune AU - Damiano M. Rovituso AU - Tjalf Ziemssen AU - Paul V. Lehmann AU - Heidi Dikow AU - Arnfin Bergmann AU - Stefanie Kuerten TI - B-Cell Activity Predicts Response to Glatiramer Acetate and Interferon in Relapsing-Remitting Multiple Sclerosis AID - 10.1212/NXI.0000000000000980 DP - 2021 May 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e980 VI - 8 IP - 3 4099 - http://nn.neurology.org/content/8/3/e980.short 4100 - http://nn.neurology.org/content/8/3/e980.full SO - Neurol Neuroimmunol Neuroinflamm2021 May 01; 8 AB - Objective We investigated the predictive value of the enzyme-linked immunospot technique (ELISPOT) in identifying patients with relapsing-remitting multiple sclerosis (RRMS) who will respond to treatment with glatiramer acetate (GA) or interferon-β (IFN-β), based on the brain-reactive B-cell activity of peripheral blood cells.Methods In this retrospective, cross-sectional, real-world multicenter study, we identified patients with RRMS in the NeuroTransData MS registry and stratified them based on their documented treatment response (relapse-free in the first 12 months of treatment) to GA or IFN-β. The GA group comprised 73 patients who responded to GA and 35 nonresponders. The IFN-β group comprised 62 responders to IFN-β and 37 nonresponders. Patients with previous or current therapy affecting B-cell activity were excluded. We polyclonally stimulated mononuclear cells from peripheral blood samples (collected after participant selection) and investigated brain-reactive B-cell activity after incubation on brain tissue lysate-coated ELISPOT plates. Validity metrics of the ELISPOT testing results were calculated (Python 3.6.8) in relation to the clinical responsiveness in the 2 treatment groups.Results The ELISPOT B-cell activity assay showed a sensitivity of 0.74, a specificity of 0.76, a positive predictive value of 0.78, a negative predictive value of 0.28, and a diagnostic OR of 8.99 in predicting clinical response to GA vs IFN-β therapy in patients with RRMS.Conclusion Measurement of brain-reactive B-cell activity by ELISPOT provides clinically meaningful predictive probabilities of individual patients' treatment response to GA or IFN-β. The assay has the potential to improve the selection of optimal first-line treatment for individual patients with RRMS.Classification of Evidence This study provides Class II evidence that in patients with RRMS, the brain reactivity of their peripheral-blood B cells predicts clinical response to GA and IFN-β.ARR=annualized relapse rate; Bcl-2=B-cell lymphoma 2; CDP=confirmed disability progression; EDSS=Expanded Disability Status Scale; ELISPOT=enzyme-linked immunospot technique; FBS=fetal bovine serum; GA=glatiramer acetate; IFN-β=interferon-β; Ig=immunoglobulin; JNK=c-Jun N-terminal kinase; NTD=NeuroTransData; PBMC=peripheral blood mononuclear cell; PBS=phosphate-buffered saline; ROC=receiver operating characteristic; RPMI=Roswell Park Memorial Institute; RRMS=relapsing-remitting MS