PMID- 33361387 OWN - NLM STAT- MEDLINE DCOM- 20211028 LR - 20211028 IS - 2332-7812 (Electronic) IS - 2332-7812 (Linking) VI - 8 IP - 2 DP - 2021 Mar TI - TDP-43-specific Autoantibody Decline in Patients With Amyotrophic Lateral Sclerosis. LID - 10.1212/NXI.0000000000000937 [doi] LID - e937 AB - OBJECTIVE: We hypothesize alterations in the quality and quantity of anti-43-kDa TAR DNA-binding protein (TDP-43) naturally occurring autoantibodies (NAbs) in patients with amyotrophic lateral sclerosis (ALS); therefore, we assessed relative binding properties of anti-TDP-43 NAbs composite in plasma from patients with ALS in comparison with healthy individuals. METHODS: ELISA competition assay was used to explore the apparent avidity/affinity of anti-TDP-43 NAbs in plasma from 51 normal controls and 30 patients with ALS. Furthermore, the relative levels of anti-TDP-43 NAbs within the immunoglobulin (Ig) classes of IgG (isotype IgG1-4) and IgMs were measured using classical indirect ELISA. The occurring results were hereafter correlated with the measures of disease duration and disease progression. RESULTS: High-avidity/affinity anti-TDP-43 NAbs levels were significantly reduced in plasma samples from patients with ALS. In addition, a significant decrease in relative levels of anti-TDP-43 IgG3 and IgM NAbs and a significant increase in anti-TDP-43 IgG4 NAbs were observed in ALS plasma vs controls. Furthermore, a decrease in global IgM and an increase in IgG4 levels were observed in ALS. These aberrations of humoral immunity correlated with disease duration, but did not correlate with ALS Functional Rating Scale-Revised scores. CONCLUSIONS: Our results may suggest TDP-43-specific immune aberrations in patients with ALS. The skewed immune profiles observed in patients with ALS could indicate a deficiency in the clearance capacity and/or blocking of TDP-43 transmission and propagation. The decrease in levels of high affinity/avidity anti-TDP-43 NAbs and IgMs correlates with disease progression and may be disease predictors. CI - Copyright (c) 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. FAU - Nielsen, Anne Kallehauge AU - Nielsen AK AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Folke, Jonas AU - Folke J AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Owczarek, Sylwia AU - Owczarek S AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Svenstrup, Kirsten AU - Svenstrup K AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Winge, Kristian AU - Winge K AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Pakkenberg, Bente AU - Pakkenberg B AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Aznar, Susana AU - Aznar S AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. FAU - Brudek, Tomasz AU - Brudek T AD - From the Research Laboratory for Stereology and Neuroscience (A.K.N., J.F., S.O., B.P., S.A., T.B.), and Department of Neurology (K.S., K.W.), Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen; Neuromuscular Clinic (K.S.), Department of Neurology, Rigshospitalet, Copenhagen; Institute of Clinical Medicine (B.P.), Faculty of Health and Medical Sciences, University of Copenhagen; and Copenhagen Center for Translational Research (S.A., T.B.), Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. tomasz.brudek@regionh.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201224 PL - United States TA - Neurol Neuroimmunol Neuroinflamm JT - Neurology(R) neuroimmunology & neuroinflammation JID - 101636388 RN - 0 (Autoantibodies) RN - 0 (Biomarkers) RN - 0 (DNA-Binding Proteins) RN - 0 (Immunoglobulin G) RN - 0 (TARDBP protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Amyotrophic Lateral Sclerosis/*blood/epidemiology/*immunology MH - Autoantibodies/*blood/*immunology MH - Biomarkers/blood MH - DNA-Binding Proteins/*blood/*immunology MH - Denmark/epidemiology MH - Female MH - Humans MH - Immunoglobulin G/blood/immunology MH - Male MH - Middle Aged MH - Young Adult PMC - PMC7768943 EDAT- 2020/12/29 06:00 MHDA- 2021/10/29 06:00 PMCR- 2020/12/24 CRDT- 2020/12/28 11:41 PHST- 2020/05/15 00:00 [received] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/12/28 11:41 [entrez] PHST- 2020/12/29 06:00 [pubmed] PHST- 2021/10/29 06:00 [medline] PHST- 2020/12/24 00:00 [pmc-release] AID - 8/2/e937 [pii] AID - NEURIMMINFL2020031054 [pii] AID - 10.1212/NXI.0000000000000937 [doi] PST - epublish SO - Neurol Neuroimmunol Neuroinflamm. 2020 Dec 24;8(2):e937. doi: 10.1212/NXI.0000000000000937. Print 2021 Mar.