IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

被引：0
作者：
Divya Thiagarajan
Nina Oparina
Susanna Lundström
Roman Zubarev
Jitong Sun
Marta Alarcon-Riquelme
Johan Frostegård
机构：
[1] Karolinska Institutet,Unit of Immunology and Chronic Disease, Institute of Environmental Medicine
[2] Karolinska Institutet,Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics
[3] GENYO,Pôle de pathologies rhumatismales systémiques et inflammatoires, Institut de Recherche Expérimentale et Clinique
[4] Center for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Government,Servicio Cantabro de Salud
[5] Parque tecnolуgico de la salud,Hospital Clinic I Provicia
[6] Referral Center for Systemic Autoimmune Diseases,Servicio Andaluz de Salud
[7] Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano,Servicio Andaluz de Salud
[8] Centre Hospitalier Universitaire de Brest,Servicio Andaluz de Salud
[9] Hospital de la Cavale Blanche,Servicio Andaluz de Salud
[10] Université catholique de Louvain,undefined
[11] Centro Hospitalar do Porto,undefined
[12] Hospital Universitario Marqués de Valdecilla,undefined
[13] Institut d’Investigacions Biomèdiques August Pi i Sunyer,undefined
[14] Katholieke Universiteit Leuven,undefined
[15] Klinikum der Universitaet zu Koeln,undefined
[16] Medizinische Hochschule Hannover,undefined
[17] Medical University Vienna,undefined
[18] Hospital Universitario Reina Sofía Córdoba,undefined
[19] Complejo hospitalario Universitario de Granada (Hospital Universitario San Cecilio),undefined
[20] Complejo hospitalario Universitario de Granada (Hospital Virgen de las Nieves),undefined
[21] Hospital Regional Universitario de Málaga,undefined
[22] Università degli studi di Milano,undefined
[23] Hospitaux Universitaires de Genève,undefined
[24] University of Szeged,undefined
[25] Charite,undefined
[26] Andalusian Public Health System Biobank,undefined
来源：
Scientific Reports | / 10卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
相关论文
共 76 条
[31]  
Wilde B(2010)Autoimmunity and the clearance of dead cells Cell 140 300-1486
[32]  
Imhof A(2005)Global natural regulatory T cell depletion in active systemic lupus erythematosus J Immunol 175 243723-43
[33]  
Nguyen TG(2006)Regulatory T cells in peripheral blood of patients with mixed connective tissue disease Scand J Rheumatol 35 2356-69
[34]  
Rahman M(2015)T Regulatory and T Helper 17 Cells in Primary Sjogren’s Syndrome: Facts and Perspectives Mediators of inflammation 2015 1333-undefined
[35]  
Barturen G(2018)Regulatory T Cells in Systemic Sclerosis Front Immunol 9 2214-undefined
[36]  
Beretta L(2001)Human-derived anti-oxidized LDL autoantibody blocks uptake of oxidized LDL by macrophages and localizes to atherosclerotic lesions Arterioscler Thromb Vasc Biol 21 1480-undefined
[37]  
Cervera R(1980)Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages Proc Natl Acad Sci USA 77 33-undefined
[38]  
Van Vollenhoven R(2010)Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis Free Radic Biol Med 49 59-undefined
[39]  
Alarcon-Riquelme ME(1999)Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines Atherosclerosis 145 7-undefined
[40]  
Sun J(2017)Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An Aspect of the Hygiene/Missing Old Friends Hypothesis Immunol Invest 46 undefined-undefined
12345678