Publication:
IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

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Date

2020-07-03

Authors

Thiagarajan, Divya
Oparina, Nina
Lundström, Susanna
Zubarev, Roman
Sun, Jitong
Alarcon-Riquelme, Marta
Frostegård, Johan

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Springer Nature
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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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Medical Subject Headings::Persons::Persons::Age Groups::Adult
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Autoantibodies
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin M
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aldehydes::Malondialdehyde
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Quaternary Ammonium Compounds::Trimethyl Ammonium Compounds::Choline::Phosphorylcholine
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics
Medical Subject Headings::Diseases::Musculoskeletal Diseases::Rheumatic Diseases
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Young Adult

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Keywords

Malondialdehyde, Phosphorylcholine, Proteomics, Rheumatic diseases, IgM, Immunoglobulin M, Malondialdehído, Fosforilcolina, Proteómica, Enfermedades reumáticas, Inmunoglobulina M

Citation

Thiagarajan D, Oparina N, Lundström S, Zubarev R, Sun J; PRECISESADS Clinical Consortium, et al. IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases. Sci Rep. 2020 Jul 3;10(1):11010