Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Atherosclerosis is characterized by activated immune competent cells and lipid oxidation, where two major epitopes forming adducts are phosphorylcholine (PC) and malondialdehyde (MDA). We here study the regulation and properties of IgM antibodies against these (anti-PC and anti-MDA) and their role in SLE where atherosclerosis and CVD are much increased.
Methods:
Peripheral blood mononuclear cells (PBMC), B, CD3 T, CD4 T and CD8 T cell were isolated from buffy coat. PBMC derived monocyte were differentiated into dendritic cells (DCs) and treated with or without PC-KLH or MDA-HSA. For activation naïve autologous T cells were co-cultured with pre-treated DCs. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plate. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti HLA II or CD40 blocking antibody were cultured 6 days. Also, CD40 was silenced and cultured similar days.
Antibody level in serum of SLE patients from the SLEVIC cohort (n=114) were compared with age- and sex-matched population-based controls (n=108). Common carotid intima-media thickness (IMT) and plaque occurrence were determined by B-mode ultrasound. Plaques were graded according to echogenicity (a measure of vulnerability).
Results:
Flow cytometry analysis showed PC-KLH and MDA-HSA stimulated DC mediated T cell activation. In addition, pro-inflammatory effects of inflammatory lipids were inhibited by anti-PC and anti-MDA.
More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plate there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti HLA II blocking antibody in mixed B and CD3 T cells culture, also inhibited by CD40 blocking antibody. In addition, CD40 role was ensured by CD40 gene silencing. Further, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production.
In serum having high levels, above 66rdpercentile, of both anti-PC and anti-MDA was a striking protection marker for plaque prevalence and vulnerability (OR 0.08, CI (0.01-0.46) and OR 0.10 and CI (0.01-0.82) respectively)
Conclusion:
Anti-MDA and anti-PC are T-cell dependent, anti-inflammatory and strong protection markers for atherosclerosis and plaque vulnerability in SLE and in general. This finding could indicate an underlying mechanism in autoimmune disease, namely low levels of natural antibodies and opens up therapeutic possibilities with these antibodies in autoimmune diseases.
To cite this abstract in AMA style:
Rahman MM, Hafström I, Liu A, Frostegård J. IgM Antibodies Against Malondialdehyde and Phosphorylcholine Are T Cell Dependent and Strong Protection Markers for Atherosclerosis in SLE [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/igm-antibodies-against-malondialdehyde-and-phosphorylcholine-are-t-cell-dependent-and-strong-protection-markers-for-atherosclerosis-in-sle/. Accessed .« Back to ACR/ARHP Annual Meeting 2015
ACR Meeting Abstracts - https://acrabstracts.org/abstract/igm-antibodies-against-malondialdehyde-and-phosphorylcholine-are-t-cell-dependent-and-strong-protection-markers-for-atherosclerosis-in-sle/