IgM antibodies against phosphorylcholine promote polarization of T regulatory cells from patients with atherosclerotic plaques, systemic lupus erythematosus and healthy donors. (January 2018)

• Record Type: Journal Article
• Authors: Sun, Jitong; Lundström, Susanna L.; Zhang, Bo; Zubarev, Roman A.; Steuer, Johnny; Gillgren, Peter; Rahman, Mizanur; Ajeganova, Sofia; Liu, Anquan; Frostegård, Johan
• Is Part Of: Atherosclerosis. Volume 268(2018)
• Page Start: 36
• Page End: 48
• Publication Date: 2018-01
• Subjects: Antibodies -- Phosphorylcholine -- T regulatory cells -- Atherosclerosis -- Autoimmunity; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2017.11.010
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: IgM antibodies against phosphorylcholine (anti-PC) are negatively associated with atherosclerosis, cardiovascular disease (CVD) and systemic lupus erythematosus (SLE), where the risk of CVD and atherosclerosis is high. We here study the effects of IgM anti-PC immune regulation. Methods: Mononuclear leukocytes were isolated from peripheral blood (PBMC) obtained from healthy blood donors, six SLE patients with age- and sex-matched controls, and symptom-giving human atherosclerotic plaques. The proportion of Th17 (CD4 + CCR6 + ) and Treg (CD4 + CD25 + CD127 dim/- ) cells was determined by flow cytometry in CD4 + T cells after 6 days of culture with Th17 or Treg-polarizing cytokines, with PMA and Ionomycin stimulation. IgM anti-PC were extracted from total IgM, with flow-through IgM as controls. Dendritic cells (DC) were differentiated from PBMC. Antibody peptide/protein characterization was done by a proteomics de novo sequencing approach. Results: IgM anti-PC increased significantly the proportion of Tregs from healthy donors, SLE patients and atherosclerotic plaque cells while control antibodies did not. T cells from SLE patients had a significantly lower proportion of Tregs and a higher proportion of Th17 cells as compared to matched controls. IgM anti-PC, but not control antibodies, significantly reduced the production of IL-17 and TNF-α in cell cultures from SLE patients and atherosclerotic plaque cells. IgM anti-PC interacted with CD40 and kept DCs in an immature stage, potentially being tolerogenic. We observed differences in the IgM peptide expression levels in anti-PC compared to control antibodies. Conclusions: IgM anti-PC promote polarization of Tregs, which could represent a novel protective mechanism in atherosclerosis and autoimmune conditions as SLE. Highlights: T cells from atherosclerotic plaque, SLE patients or controls were treated with IgM anti-phosphorylcholine(anti-PC). Anti-PC increased Tregs in all groups, and in SLE from a low level to normal level and kept DC in an immature stage. We identify differences on the IgM peptide expression level in anti-PC compared to control antibodies. IgM anti-PC promotes polarization of Tregs which could be a protective mechanism in atherosclerosis and SLE.