Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) show autoantibodies against post-translational protein modifications (PTMs), such as anti-citrullinated protein antibodies. However, the range of recognized PTMs is unknown. Here, we addressed four PTMs: chlorination, non-enzymatic glycation, nitration, and ho...

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Main Authors: Lorena Rodríguez-Martínez, Cristina Regueiro, Sámer Amhaz-Escanlar, Carmen Pena, Paloma Herbello-Hermelo, Antonio Moreda-Piñeiro, Javier Rodriguez-Garcia, Antonio Mera-Varela, Eva Pérez-Pampín, Antonio González
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/12/2/352
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author Lorena Rodríguez-Martínez
Cristina Regueiro
Sámer Amhaz-Escanlar
Carmen Pena
Paloma Herbello-Hermelo
Antonio Moreda-Piñeiro
Javier Rodriguez-Garcia
Antonio Mera-Varela
Eva Pérez-Pampín
Antonio González
author_facet Lorena Rodríguez-Martínez
Cristina Regueiro
Sámer Amhaz-Escanlar
Carmen Pena
Paloma Herbello-Hermelo
Antonio Moreda-Piñeiro
Javier Rodriguez-Garcia
Antonio Mera-Varela
Eva Pérez-Pampín
Antonio González
author_sort Lorena Rodríguez-Martínez
collection DOAJ
description Patients with rheumatoid arthritis (RA) show autoantibodies against post-translational protein modifications (PTMs), such as anti-citrullinated protein antibodies. However, the range of recognized PTMs is unknown. Here, we addressed four PTMs: chlorination, non-enzymatic glycation, nitration, and homocysteinylation, identified as targets of atypical RA autoantibodies in studies whose protocols we have followed. The modified antigens included collagen type II, an extract of synovial proteins and a selection of peptides. We interpreted the results according to the optical density (OD) obtained in an enzyme-linked immunosorbent assay ( ELISA) with the modified antigen and the corrected OD obtained after subtracting the reactivity against the unmodified antigen. The results showed evidence of specific antibodies against glycated collagen type II, as the corrected ODs were higher in the 182 patients with RA than in the 164 healthy controls (<i>p</i> = 0.0003). However, the relevance of these antibodies was doubtful because the magnitude of the specific signal was small (median OD = 0.072 vs. 0.027, respectively). There were no specific antibodies against any of the other three PTMs. Therefore, our results showed that the four PTMs are not inducing a significant autoantibody response in patients with RA. These results indicated that the repertoire of PTM autoantigens in RA is restricted.
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spelling doaj.art-3f09cc9b925e4015b598fe39b05e58482023-11-23T19:30:38ZengMDPI AGDiagnostics2075-44182022-01-0112235210.3390/diagnostics12020352Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid ArthritisLorena Rodríguez-Martínez0Cristina Regueiro1Sámer Amhaz-Escanlar2Carmen Pena3Paloma Herbello-Hermelo4Antonio Moreda-Piñeiro5Javier Rodriguez-Garcia6Antonio Mera-Varela7Eva Pérez-Pampín8Antonio González9Experimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainDepartment of Orthopedic Surgery and Traumatology, Instituto de Investigación Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainTrace Element, Spectroscopy and Speciation Group (GETEE), Strategic Grouping in Materials (AEMAT), Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainTrace Element, Spectroscopy and Speciation Group (GETEE), Strategic Grouping in Materials (AEMAT), Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainDepartment of Clinical Analysis, Instituto de Investigación Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainExperimental and Observational Rheumatology and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clínico Universitario de Santiago (IDIS), 15706 Santiago de Compostela, SpainPatients with rheumatoid arthritis (RA) show autoantibodies against post-translational protein modifications (PTMs), such as anti-citrullinated protein antibodies. However, the range of recognized PTMs is unknown. Here, we addressed four PTMs: chlorination, non-enzymatic glycation, nitration, and homocysteinylation, identified as targets of atypical RA autoantibodies in studies whose protocols we have followed. The modified antigens included collagen type II, an extract of synovial proteins and a selection of peptides. We interpreted the results according to the optical density (OD) obtained in an enzyme-linked immunosorbent assay ( ELISA) with the modified antigen and the corrected OD obtained after subtracting the reactivity against the unmodified antigen. The results showed evidence of specific antibodies against glycated collagen type II, as the corrected ODs were higher in the 182 patients with RA than in the 164 healthy controls (<i>p</i> = 0.0003). However, the relevance of these antibodies was doubtful because the magnitude of the specific signal was small (median OD = 0.072 vs. 0.027, respectively). There were no specific antibodies against any of the other three PTMs. Therefore, our results showed that the four PTMs are not inducing a significant autoantibody response in patients with RA. These results indicated that the repertoire of PTM autoantigens in RA is restricted.https://www.mdpi.com/2075-4418/12/2/352rheumatoid arthritisautoantibodiespost-translational protein modificationschlorinationnon-enzymatic glycationnitration
spellingShingle Lorena Rodríguez-Martínez
Cristina Regueiro
Sámer Amhaz-Escanlar
Carmen Pena
Paloma Herbello-Hermelo
Antonio Moreda-Piñeiro
Javier Rodriguez-Garcia
Antonio Mera-Varela
Eva Pérez-Pampín
Antonio González
Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
Diagnostics
rheumatoid arthritis
autoantibodies
post-translational protein modifications
chlorination
non-enzymatic glycation
nitration
title Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
title_full Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
title_fullStr Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
title_full_unstemmed Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
title_short Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis
title_sort antibodies against 4 atypical post translational protein modifications in patients with rheumatoid arthritis
topic rheumatoid arthritis
autoantibodies
post-translational protein modifications
chlorination
non-enzymatic glycation
nitration
url https://www.mdpi.com/2075-4418/12/2/352
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