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Humoral response to neurofilaments and dipeptide repeats in ALS progression
OBJECTIVE: To appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS). METHODS: Antibodies and immune complexes against neurofil...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419401/ https://www.ncbi.nlm.nih.gov/pubmed/34318620 http://dx.doi.org/10.1002/acn3.51428 |
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author | Puentes, Fabiola Lombardi, Vittoria Lu, Ching‐Hua Yildiz, Ozlem Fratta, Pietro Isaacs, Adrian Bobeva, Yoana Wuu, Joanne Benatar, Michael Malaspina, Andrea |
author_facet | Puentes, Fabiola Lombardi, Vittoria Lu, Ching‐Hua Yildiz, Ozlem Fratta, Pietro Isaacs, Adrian Bobeva, Yoana Wuu, Joanne Benatar, Michael Malaspina, Andrea |
author_sort | Puentes, Fabiola |
collection | PubMed |
description | OBJECTIVE: To appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS). METHODS: Antibodies and immune complexes against neurofilament light, medium, heavy chains as well as poly‐(GP)‐(GR) dipeptide repeats were measured in blood samples from the ALS Biomarkers (n = 107) and the phenotype–genotype biomarker (n = 129) studies and in 140 healthy controls. Target analyte levels were studied longitudinally in 37 ALS cases. Participants were stratified according to the rate of disease progression estimated before and after baseline and C9orf72 genetic status. Survival and longitudinal analyses were undertaken with reference to matched neurofilament protein expression. RESULTS: Compared to healthy controls, total neurofilament proteins and antibodies, neurofilament light immune complexes (p < 0.0001), and neurofilament heavy antibodies (p = 0.0061) were significantly elevated in ALS, patients with faster progressing disease (p < 0.0001) and in ALS cases with a C9orf72 mutation (p < 0.0003). Blood neurofilament light protein discriminated better ALS from healthy controls (AUC: 0.92; p < 0.0001) and faster from slower progressing ALS (AUC: 0.86; p < 0.0001) compared to heavy‐chain antibodies and light‐chain immune complexes (AUC: 0.79; p < 0.0001 and AUC: 0.74; p < 0.0001). Lower neurofilament heavy antibodies were associated with longer survival (Log‐rank Chi‐square: 7.39; p = 0.0065). Increasing levels of antibodies and immune complexes between time points were observed in faster progressing ALS. CONCLUSIONS: We report a distinctive humoral response characterized by raising antibodies against neurofilaments and dipeptide repeats in faster progressing and C9orf72 genetic mutation carriers ALS patients. We confirm the significance of plasma neurofilament proteins in the clinical stratification of ALS. |
format | Online Article Text |
id | pubmed-8419401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84194012021-09-08 Humoral response to neurofilaments and dipeptide repeats in ALS progression Puentes, Fabiola Lombardi, Vittoria Lu, Ching‐Hua Yildiz, Ozlem Fratta, Pietro Isaacs, Adrian Bobeva, Yoana Wuu, Joanne Benatar, Michael Malaspina, Andrea Ann Clin Transl Neurol Research Articles OBJECTIVE: To appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS). METHODS: Antibodies and immune complexes against neurofilament light, medium, heavy chains as well as poly‐(GP)‐(GR) dipeptide repeats were measured in blood samples from the ALS Biomarkers (n = 107) and the phenotype–genotype biomarker (n = 129) studies and in 140 healthy controls. Target analyte levels were studied longitudinally in 37 ALS cases. Participants were stratified according to the rate of disease progression estimated before and after baseline and C9orf72 genetic status. Survival and longitudinal analyses were undertaken with reference to matched neurofilament protein expression. RESULTS: Compared to healthy controls, total neurofilament proteins and antibodies, neurofilament light immune complexes (p < 0.0001), and neurofilament heavy antibodies (p = 0.0061) were significantly elevated in ALS, patients with faster progressing disease (p < 0.0001) and in ALS cases with a C9orf72 mutation (p < 0.0003). Blood neurofilament light protein discriminated better ALS from healthy controls (AUC: 0.92; p < 0.0001) and faster from slower progressing ALS (AUC: 0.86; p < 0.0001) compared to heavy‐chain antibodies and light‐chain immune complexes (AUC: 0.79; p < 0.0001 and AUC: 0.74; p < 0.0001). Lower neurofilament heavy antibodies were associated with longer survival (Log‐rank Chi‐square: 7.39; p = 0.0065). Increasing levels of antibodies and immune complexes between time points were observed in faster progressing ALS. CONCLUSIONS: We report a distinctive humoral response characterized by raising antibodies against neurofilaments and dipeptide repeats in faster progressing and C9orf72 genetic mutation carriers ALS patients. We confirm the significance of plasma neurofilament proteins in the clinical stratification of ALS. John Wiley and Sons Inc. 2021-07-27 /pmc/articles/PMC8419401/ /pubmed/34318620 http://dx.doi.org/10.1002/acn3.51428 Text en © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Puentes, Fabiola Lombardi, Vittoria Lu, Ching‐Hua Yildiz, Ozlem Fratta, Pietro Isaacs, Adrian Bobeva, Yoana Wuu, Joanne Benatar, Michael Malaspina, Andrea Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title | Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title_full | Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title_fullStr | Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title_full_unstemmed | Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title_short | Humoral response to neurofilaments and dipeptide repeats in ALS progression |
title_sort | humoral response to neurofilaments and dipeptide repeats in als progression |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419401/ https://www.ncbi.nlm.nih.gov/pubmed/34318620 http://dx.doi.org/10.1002/acn3.51428 |
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