IgM anti-phosphorylcholine antibodies associate with senescent and IL-17+ T cells in SLE patients with a pro-inflammatory lipid profile. (13th July 2019)

• Record Type: Journal Article
• Authors: López, Patricia; Rodríguez-Carrio, Javier; Martínez-Zapico, Aleida; Pérez-Álvarez, Ángel I; Benavente, Lorena; Caminal-Montero, Luis; Suárez, Ana
• Is Part Of: Rheumatology. Volume 59:Number 2(2020)
• Page Start: 407
• Page End: 417
• Publication Date: 2019-07-13
• Subjects: atherosclerosis -- IgM anti-phosphorylcholine antibodies -- lipid profile -- Th17 -- Treg -- CD4+CD28null cells -- systemic lupus erythematosus; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/kez264
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objective: The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. Methods: Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4 + CD28 null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls. Results: IgM anti-PC serum levels were reduced in SLE patients compared with controls ( P < 0.001) and were associated with age (β= −0.252; P = 0.002), high-density lipoprotein (HDL; β = 0.271; P = 0.001), low-density lipoprotein (LDL; β= −0.192; P = 0.017) and glucocorticoid treatment (β= −0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased ( P = 0.007) and associated with age (β = 0.194; P = 0.028) and SLEDAI (β = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage ( P = 0.001). CD4 + CD28 null and Th17 cells were increased in SLE patients compared with controls ( P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4 + CD28 null : β = −0.455, P = 0.001; Th17: β= −0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines. Conclusion: The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role.