Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis

Abstract Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in se...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elisa Conti, Gessica Sala, Susanna Diamanti, Marco Casati, Christian Lunetta, Francesca Gerardi, Claudia Tarlarini, Lorena Mosca, Nilo Riva, Yuri Falzone, Massimo Filippi, Ildebrando Appollonio, Carlo Ferrarese, Lucio Tremolizzo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ef5762f44e5483381b6ff5311429ca6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9ef5762f44e5483381b6ff5311429ca6
record_format	dspace
spelling	oai:doaj.org-article:9ef5762f44e5483381b6ff5311429ca62021-12-02T11:50:30ZSerum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis10.1038/s41598-021-81599-52045-2322https://doaj.org/article/9ef5762f44e5483381b6ff5311429ca62021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81599-5https://doaj.org/toc/2045-2322Abstract Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer’s disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.Elisa ContiGessica SalaSusanna DiamantiMarco CasatiChristian LunettaFrancesca GerardiClaudia TarlariniLorena MoscaNilo RivaYuri FalzoneMassimo FilippiIldebrando AppollonioCarlo FerrareseLucio TremolizzoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisa Conti Gessica Sala Susanna Diamanti Marco Casati Christian Lunetta Francesca Gerardi Claudia Tarlarini Lorena Mosca Nilo Riva Yuri Falzone Massimo Filippi Ildebrando Appollonio Carlo Ferrarese Lucio Tremolizzo Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
description	Abstract Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before. In this exploratory study, we quantified the levels of both anti-TDP-43 NAb and TDP-43 protein as putative accessible markers for improving the ALS diagnostic process by using ELISA in N = 70 ALS patients (N = 4 carrying TARDBP mutations), N = 40 age-comparable healthy controls (CTRL), N = 20 motor neuron disease mimics (MN-m), N = 20 Alzheimer’s disease (AD) and N = 15 frontotemporal lobar degeneration (FTLD) patients. Anti-TDP-43 NAb were found to be significantly increased in ALS patients compared to all the other groups (p < 0.001). On the other hand, the distribution of serum levels of TDP-43 protein was highly variable among the various groups. Levels were increased in ALS patients, albeit the highest values were detected in MN-m patients. NAb and protein serum levels failed to correlate. For the first time, we report that serum anti-TDP-43 NAb are detectable in human serum of both healthy controls and patients affected by a variety of neurodegenerative disorders; furthermore, their levels are increased in ALS patients, representing a potentially interesting trait core marker of this disease. Further studies are needed to clarify the exact role of the NAb. This information might be extremely useful for paving the way toward targeting TDP-43 by immunotherapy in ALS.
format	article
author	Elisa Conti Gessica Sala Susanna Diamanti Marco Casati Christian Lunetta Francesca Gerardi Claudia Tarlarini Lorena Mosca Nilo Riva Yuri Falzone Massimo Filippi Ildebrando Appollonio Carlo Ferrarese Lucio Tremolizzo
author_facet	Elisa Conti Gessica Sala Susanna Diamanti Marco Casati Christian Lunetta Francesca Gerardi Claudia Tarlarini Lorena Mosca Nilo Riva Yuri Falzone Massimo Filippi Ildebrando Appollonio Carlo Ferrarese Lucio Tremolizzo
author_sort	Elisa Conti
title	Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
title_short	Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
title_full	Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
title_fullStr	Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
title_full_unstemmed	Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis
title_sort	serum naturally occurring anti-tdp-43 auto-antibodies are increased in amyotrophic lateral sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9ef5762f44e5483381b6ff5311429ca6
work_keys_str_mv	AT elisaconti serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT gessicasala serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT susannadiamanti serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT marcocasati serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT christianlunetta serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT francescagerardi serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT claudiatarlarini serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT lorenamosca serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT niloriva serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT yurifalzone serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT massimofilippi serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT ildebrandoappollonio serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT carloferrarese serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis AT luciotremolizzo serumnaturallyoccurringantitdp43autoantibodiesareincreasedinamyotrophiclateralsclerosis
_version_	1718395180864765952

Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis

Ejemplares similares