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.
Highlights
IgM antibodies against phosphorylcholine and malondialdehyde may have protective properties in cardiovascular and rheumatic diseases
It is negatively associated with cardiovascular disease including stroke and myocardial infarction (MI), atherosclerosis increase after four years, and mortality after MI12–14
We demonstrate that for the combined patient cohort anti-PC IgM is significantly negatively correlated with the Cardiovascular score (CV) score, but not anti-MDA (Spearman’s rank correlation p-value 8.3E-05, 8.6-E07 and 0.64)
Summary
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. PRECISESADS (Precision medicine strategies for Systemic Autoimmune Diseases) patients with various autoimmune diseases: SLE (Systemic Lupus Erythematosus), RA (Rheumatoid Arthritis), SjS (Sjögrens syndrome), SSc (Systemic Sclerosis), MCTD (Mixed Connective Tissue Disease), PAPs (Primary Antiphospholipid syndrome) and UCTD (Undifferentiated Connective Tissue Disease), were recruited. We have reported protective associations for IgM anti-PC in different chronic inflammatory disease conditions. It is negatively associated with cardiovascular disease including stroke and myocardial infarction (MI), atherosclerosis increase after four years, and mortality after MI12–14. These and similar findings have largely been confirmed and extended into other diseases like vasculitis and even osteoarthritis[19,20,21,22,23,24,25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
