IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases
Authors: Thiagarajan Divya , Oparina Nina , Lundström Susanna , Zubarev Roman , Sun Jitong ,   The PRECISESADS Clinical Consortium, Beretta Lorenzo , Vigone Barbara , Pers Jacques-Olivier , Saraux Alain , Devauchelle-Pensec Valérie , Cornec Divi , Jousse-Joulin Sandrine , Lauwerys Bernard , Ducreux Julie , Maudoux Anne-Lise , Vasconcelos Carlos , Tavares Ana , Neves Esmeralda , Faria Raquel , Brandão Mariana , Campar Ana , Marinho António , Farinha Fátima , Almeida Isabel , Mantecón Miguel Angel Gonzalez-Gay , Alonso Ricardo Blanco , Martínez Alfonso Corrales , Cervera Ricard , Rodríguez-Pintó Ignasi , Espinosa Gerard , Lories Rik , Langhe Ellen De , Hunzelmann Nicolas , Belz Doreen , Witte Torsten , Baerlecken Niklas , Stummvoll Georg , Zauner Michael , Lehner Michaela , Collantes Eduardo , Ortega-Castro Rafaela , Aguirre-Zamorano Mª Angeles , Escudero-Contreras Alejandro , Castro-Villegas Mª Carmen , Ortego Norberto , Roldán María Concepción Fernández , Raya Enrique , Moleón Inmaculada Jiménez , de Ramon Enrique , Quintero Isabel Díaz , Meroni Pier Luigi , Gerosa Maria , Schioppo Tommaso , Artusi Carolina , Chizzolini Carlo , Zuber Aleksandra , Wynar Donatienne , Kovács Laszló , Balog Attila , Deák Magdolna , Bocskai Márta , Dulic Sonja , Kádár Gabriella , Hiepe Falk , Gerl Velia , Thiel Silvia , Maresca Manuel Rodriguez , López-Berrio Antonio , Aguilar-Quesada Rocío , Navarro-Linares Héctor , Alarcon-Riquelme Marta , Frostegård Johan 
Published: July 2020

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.