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IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

Authors
  • Thiagarajan, Divya1
  • Oparina, Nina1
  • Lundström, Susanna1
  • Zubarev, Roman1
  • Sun, Jitong1
  • Beretta, Lorenzo2
  • Vigone, Barbara2
  • Pers, Jacques-Olivier3
  • Saraux, Alain3
  • Devauchelle-Pensec, Valérie3
  • Cornec, Divi3
  • Jousse-Joulin, Sandrine3
  • Lauwerys, Bernard4
  • Ducreux, Julie4
  • Maudoux, Anne-Lise4
  • Vasconcelos, Carlos5
  • Tavares, Ana5
  • Neves, Esmeralda5
  • Faria, Raquel5
  • Brandão, Mariana5
  • And 50 more
  • 1 Karolinska Institutet, Stockholm, Sweden , Stockholm (Sweden)
  • 2 Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy , Milan (Italy)
  • 3 Centre Hospitalier Universitaire de Brest, Hospital de la Cavale Blanche, Brest, France , Brest (France)
  • 4 Université catholique de Louvain, Brussels, Belgium , Brussels (Belgium)
  • 5 Centro Hospitalar do Porto, Porto, Portugal , Porto (Portugal)
  • 6 Hospital Universitario Marqués de Valdecilla, Santander, Spain , Santander (Spain)
  • 7 Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain , Barcelona (Spain)
  • 8 Katholieke Universiteit Leuven, Leuven, Belgium , Leuven (Belgium)
  • 9 Klinikum der Universitaet zu Koeln, Cologne, Germany , Cologne (Germany)
  • 10 Medizinische Hochschule Hannover, Hanover, Germany , Hanover (Germany)
  • 11 Medical University Vienna, Vienna, Austria , Vienna (Austria)
  • 12 Hospital Universitario Reina Sofía Córdoba, Córdoba, Spain , Córdoba (Spain)
  • 13 Complejo hospitalario Universitario de Granada (Hospital Universitario San Cecilio), Granada, Spain , Granada (Spain)
  • 14 Complejo hospitalario Universitario de Granada (Hospital Virgen de las Nieves), Granada, Spain , Granada (Spain)
  • 15 Hospital Regional Universitario de Málaga, Málaga, Spain , Málaga (Spain)
  • 16 Università degli studi di Milano, Milan, Italy , Milan (Italy)
  • 17 Hospitaux Universitaires de Genève, Geneva, Switzerland , Geneva (Switzerland)
  • 18 University of Szeged, Szeged, Hungary , Szeged (Hungary)
  • 19 Charite, Berlin, Germany , Berlin (Germany)
  • 20 Andalusian Public Health System Biobank, Granada, Spain , Granada (Spain)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Jul 03, 2020
Volume
10
Issue
1
Identifiers
DOI: 10.1038/s41598-020-66981-z
Source
Springer Nature
License
Green

Abstract

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren’s syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions.

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