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Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations

BACKGROUND: Although autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have been studied extensively in rheumatoid arthritis and asso...

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Autores principales: Monahan, Rory C, van den Beukel, Michelle D, Borggreven, Nicole V, Fronczek, Rolf, Huizinga, Tom W J, Kloppenburg, Margreet, Steup-Beekman, Gerda M, Trouw, Leendert A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024229/
https://www.ncbi.nlm.nih.gov/pubmed/35450955
http://dx.doi.org/10.1136/rmdopen-2021-002079
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author Monahan, Rory C
van den Beukel, Michelle D
Borggreven, Nicole V
Fronczek, Rolf
Huizinga, Tom W J
Kloppenburg, Margreet
Steup-Beekman, Gerda M
Trouw, Leendert A
author_facet Monahan, Rory C
van den Beukel, Michelle D
Borggreven, Nicole V
Fronczek, Rolf
Huizinga, Tom W J
Kloppenburg, Margreet
Steup-Beekman, Gerda M
Trouw, Leendert A
author_sort Monahan, Rory C
collection PubMed
description BACKGROUND: Although autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have been studied extensively in rheumatoid arthritis and associate with disease progression. While PTMs have also been detected in patients with SLE, studies on anti-PTM antibodies remain scarce. We studied the presence of anti-PTM antibodies in SLE and neuropsychiatric SLE (NPSLE), a manifestation that lacks serological markers. METHODS: IgG antibody responses against six PTMs (malondialdehyde–acetaldehyde adducts (MAA), advanced glycation end-products (AGE), carbamylation (CarP), citrullination, acetylation and nitration) were tested using ELISA in sera of 349 patients with SLE (mean age 44±13 years; 87% female) and compared with 108 healthy controls. Levels and positivity were correlated with clinical features and SLE manifestations. RESULTS: Anti-MAA, anti-AGE and anti-CarP antibodies were more prevalent in SLE compared with controls (MAA: 29% vs 3%, AGE: 18% vs 4%, CarP: 14% vs 5%, all p≤0.0001). Anti-MAA and anti-AGE antibodies correlated with clinical manifestations and serological inflammatory markers. Patients with major NPSLE showed higher positivity of anti-MAA (39% vs 24%, p=0.01) and anti-CarP antibodies (20% vs 11%, p=0.04) than patients without major NPSLE. In addition, anti-PTM antibody levels correlated with brain volumes, an objective measure of nervous system involvement. CONCLUSIONS: In our NPSLE cohort, a subset of patients with SLE have anti-PTM antibodies against MAA, AGE and CarP modified proteins. Interestingly, anti-MAA and anti-CarP were more prevalent in NPSLE, a manifestation for which no biomarkers exist.
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spelling pubmed-90242292022-05-06 Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations Monahan, Rory C van den Beukel, Michelle D Borggreven, Nicole V Fronczek, Rolf Huizinga, Tom W J Kloppenburg, Margreet Steup-Beekman, Gerda M Trouw, Leendert A RMD Open Lupus BACKGROUND: Although autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have been studied extensively in rheumatoid arthritis and associate with disease progression. While PTMs have also been detected in patients with SLE, studies on anti-PTM antibodies remain scarce. We studied the presence of anti-PTM antibodies in SLE and neuropsychiatric SLE (NPSLE), a manifestation that lacks serological markers. METHODS: IgG antibody responses against six PTMs (malondialdehyde–acetaldehyde adducts (MAA), advanced glycation end-products (AGE), carbamylation (CarP), citrullination, acetylation and nitration) were tested using ELISA in sera of 349 patients with SLE (mean age 44±13 years; 87% female) and compared with 108 healthy controls. Levels and positivity were correlated with clinical features and SLE manifestations. RESULTS: Anti-MAA, anti-AGE and anti-CarP antibodies were more prevalent in SLE compared with controls (MAA: 29% vs 3%, AGE: 18% vs 4%, CarP: 14% vs 5%, all p≤0.0001). Anti-MAA and anti-AGE antibodies correlated with clinical manifestations and serological inflammatory markers. Patients with major NPSLE showed higher positivity of anti-MAA (39% vs 24%, p=0.01) and anti-CarP antibodies (20% vs 11%, p=0.04) than patients without major NPSLE. In addition, anti-PTM antibody levels correlated with brain volumes, an objective measure of nervous system involvement. CONCLUSIONS: In our NPSLE cohort, a subset of patients with SLE have anti-PTM antibodies against MAA, AGE and CarP modified proteins. Interestingly, anti-MAA and anti-CarP were more prevalent in NPSLE, a manifestation for which no biomarkers exist. BMJ Publishing Group 2022-04-21 /pmc/articles/PMC9024229/ /pubmed/35450955 http://dx.doi.org/10.1136/rmdopen-2021-002079 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Lupus
Monahan, Rory C
van den Beukel, Michelle D
Borggreven, Nicole V
Fronczek, Rolf
Huizinga, Tom W J
Kloppenburg, Margreet
Steup-Beekman, Gerda M
Trouw, Leendert A
Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title_full Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title_fullStr Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title_full_unstemmed Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title_short Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
title_sort autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations
topic Lupus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024229/
https://www.ncbi.nlm.nih.gov/pubmed/35450955
http://dx.doi.org/10.1136/rmdopen-2021-002079
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