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Author Spotlight: Novel Assay for Studying B-Cell Responses in Multiple Sclerosis Research
Published on: December 1, 2023
Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis
Imke Metz1, Tim Beißbarth1, David Ellenberger1
1Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
Objective:
To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)-positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS).
Methods:
We screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20).
Results:
Differential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well-discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD.
Conclusions:
While AQP4-Ab-positive and -negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS.
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