Serum lipoprotein‐associated phospholipase A2 activity in Chinese patients with systemic lupus erythematosus
)Graphical Abstract
Abstract
Few studies have explored the association between lipoprotein‐associated phospholipase A2 (Lp‐PLA2) and systemic lupus erythematosus (SLE). However, most of these studies have investigated only European patient populations and have come to contradictory conclusions. Furthermore, few studies have been conducted on Chinese patient groups. This study aimed to explore the association between serum Lp‐PLA2 activity and SLE in a Chinese patient group.
Serum Lp‐PLA2 activity was detected in 154 SLE patients and 55 age‐, sex‐, and body mass index‐matched healthy controls. Information concerning the anthropometric data, clinical manifestations, SLE Disease Activity Index 2000 (SLEDAI‐2K), complement C3 (C3), and complement C4 (C4) erythrocyte sedimentation rate (ESR), and autoantibodies were evaluated.
The average level of serum Lp‐PLA2 activity was 221 ± 56 U/L in SLE patients compared with 160 ± 37 U/L in healthy controls (p < 0.001). SLE patients that presented with nephritis, anemia, and fibrinolytic abnormality had higher serum Lp‐PLA2 activity than SLE patients who did not present with these symptoms (p < 0.05), and the levels of serum Lp‐PLA2 activity correlated with the severity of the clinical manifestations (p < 0.001). There was no correlation between serum Lp‐PLA2 activity and serum autoantibodies levels (p > 0.05). According to Spearman’s rank correlation coefficient, ESR, SLEDAI‐2K, C3, and C4 significantly correlated with serum Lp‐PLA2 activity (p < 0.001). According to binary logistic regression, Lp‐PLA2 activity was independently associated with active SLE in patients (OR 1.049; 95% CI: 1.025–1.073, p < 0.001).
Serum Lp‐PLA2 activity is associated with some clinical manifestations (nephritis, anemia, and fibrinolytic abnormality) in SLE patients, and its activity may contribute to the development of SLE disease. These findings provide new insight into the pathogenesis of SLE.
Keywords
References
Stojan G, Petri M. Epidemiology of systemic lupus erythematosus: an update. Curr Opin Rheumatol. 2018;30(2):144–50. https://doi.org/10.1097/BOR.0000000000000480
Zen M, Salmaso L, Barbiellini Amidei C, Fedeli U, Bellio S, Iaccarino L, et al. Mortality and causes of death in systemic lupus erythematosus over the last decade: data from a large population‐based study. Eur J Intern Med. 2023;112:45–51. https://doi.org/10.1016/j.ejim.2023.02.004
Ceccarelli F, Perricone C, Massaro L, Cipriano E, Alessandri C, Spinelli FR, et al. Assessment of disease activity in systemic lupus erythematosus: lights and shadows. Autoimmun Rev. 2015;14(7):601–8. https://doi.org/10.1016/j.autrev.2015.02.008
Accapezzato D, Caccavale R, Paroli MP, Gioia C, Nguyen BL, Spadea L, et al. Advances in the pathogenesis and treatment of systemic lupus erythematosus. Int J Mol Sci. 2023;24(7):6578. https://doi.org/10.3390/ijms24076578
Wu CY, Li CF, Wu QJ, Xu JH, Jiang LD, Gong L, et al. Chinese systemic lupus erythematosus treatment and research group registry Ⅸ: clinical features and survival of childhood‐onset systemic lupus erythematosus in China. Chin Med J. 2017;130(11):1276–82. https://doi.org/10.4103/0366-6999.206346
Muñoz‐Grajales C, Yilmaz EB, Svenungsson E, Touma Z. Systemic lupus erythematosus and damage: what has changed over the past 20 years? Best Pract Res Clin Rheumatol. 2023;37(4):101893. https://doi.org/10.1016/j.berh.2023.101893
Lou H, Ling GS, Cao X. Autoantibodies in systemic lupus erythematosus: from immunopathology to therapeutic target. J Autoimmun. 2022;132:102861. https://doi.org/10.1016/j.jaut.2022.102861
Davidson MH, Corson MA, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, et al. Consensus panel recommendation for incorporating lipoprotein‐associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol. 2008;101(12):S51–7. https://doi.org/10.1016/j.amjcard.2008.04.019
Gu X, Hou J, Yang S, Yu H, Tian J, Liu F, et al. Is lipoprotein‐associated phospholipase A2 activity correlated with fibrous‐cap thickness and plaque volume in patients with acute coronary syndrome? Coron Artery Dis. 2014;25(1):10–5. https://doi.org/10.1097/MCA.0000000000000041
Nezos A, Skarlis C, Psarrou A, Markakis K, Garantziotis P, Papanikolaou A, et al. Lipoprotein‐associated phospholipase A2: a novel contributor in Sjögren’s syndrome‐related lymphoma? Front Immunol. 2021;12:683623. https://doi.org/10.3389/fimmu.2021.683623
Tetta C, Bussolino F, Modena V, Montrucchio G, Segoloni G, Pescarmona G, et al. Release of platelet‐activating factor in systemic lupus erythematosus. Int Arch Allergy Appl Immunol. 1990;91(3):244–56. https://doi.org/10.1159/000235124
Denizot Y, Liozon E, Guglielmi L, Ly K, Soria P, Loustaud V, et al. No evidence for a putative involvement of platelet‐activating factor in systemic lupus erythematosus without active nephritis. Mediat Inflamm. 2003;12(2):101–5. https://doi.org/10.1080/0962935031000097718
Kotlęga D, Gołąb‐Janowska M, Masztalewicz M, Ciećwież S, Nowacki P. Association between selected gene polymorphisms and statin metabolism, risk of ischemic stroke and cardiovascular disorders. Postepy Hig Med Dosw. 2016;70:435–47. https://doi.org/10.5604/17322693.1201197
Ridker PM, MacFadyen JG, Wolfert RL, Koenig W. Relationship of lipoprotein‐associated phospholipase A2 mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: an analysis from the JUPITER trial. Clin Chem. 2012;58(5):877–86. https://doi.org/10.1373/clinchem.2011.180281
Cederholm A, Svenungsson E, Stengel D, Fei GZ, Pockley AG, Ninio E, et al. Platelet‐activating factor‐acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum. 2004;50(9):2869–76. https://doi.org/10.1002/art.20432
Gómez‐Puerta JA, Barbhaiya M, Guan H, Feldman CH, Alarcón GS, Costenbader KH. Racial/ethnic variation in all‐cause mortality among United States Medicaid recipients with systemic lupus erythematosus: a Hispanic and Asian paradox. Arthritis Rheumatol. 2015;67(3):752–60. https://doi.org/10.1002/art.38981
Gregson J, Stirnadel‐Farrant HA, Doobaree IU, Koro C. Variation of lipoprotein associated phospholipase A2 across demographic characteristics and cardiovascular risk factors: a systematic review of the literature. Atherosclerosis. 2012;225(1):11–21. https://doi.org/10.1016/j.atherosclerosis.2012.06.020
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288–91.
Robinson GA, Wilkinson MGL, Wincup C. The role of immunometabolism in the pathogenesis of systemic lupus erythematosus. Front Immunol. 2022;12:806560. https://doi.org/10.3389/fimmu.2021.806560
Ulrich C, Trojanowicz B, Fiedler R, Kohler F, Wolf AF, Seibert E, et al. Differential expression of lipoprotein‐associated phospholipase A2 in monocyte subsets: impact of uremia and atherosclerosis. Nephron. 2017;135(3):231–41. https://doi.org/10.1159/000454778
Yang S, Chen XY, Xu XP. The relationship between lipoprotein‐associated phospholipase A(2), cholesteryl ester transfer protein and lipid profile and risk of atherosclerosis in women with iron deficiency anaemia. Clin Lab. 2015;61(10):1463–9. https://doi.org/10.7754/clin.lab.2015.150202
Ragab SM, Safan MA, Obeid OM, Sherief AS. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) and tumor necrosis factor‐alpha (TNF‐α) and their relation to premature atherosclerosis in β‐thalassemia children. Hematology. 2015;20(4):228–38. https://doi.org/10.1179/1607845414Y.0000000180
Kim M, Yoo HJ, Lee D, Lee JH. Oxidized LDL induces procoagulant profiles by increasing lysophosphatidylcholine levels, lysophosphatidylethanolamine levels, and Lp‐PLA2 activity in borderline hypercholesterolemia. Nutr Metabol Cardiovasc Dis. 2020;30(7):1137–46. https://doi.org/10.1016/j.numecd.2020.03.015
Frostegård J. Systemic lupus erythematosus and cardiovascular disease. J Intern Med. 2023;293(1):48–62. https://doi.org/10.1111/joim.13557
Zheng H, Cui D, Quan X, Yang W, Li Y, Zhang L, et al. Lp‐PLA2 silencing protects against ox‐LDL‐induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages. Biochem Biophys Res Commun. 2016;477(4):1017–23. https://doi.org/10.1016/j.bbrc.2016.07.022
Xiong H, Cui M, Kong N, Jing J, Xu Y, Liu X, et al. Cytotoxic CD161‐CD8+ TEMRA cells contribute to the pathogenesis of systemic lupus erythematosus. EBioMedicine. 2023;90:104507. https://doi.org/10.1016/j.ebiom.2023.104507
Zhang F, Liu W, Meng F, Jiang Q, Tang W, Liu Z, et al. Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma. J Immunother Cancer. 2024;12(1):e008094. https://doi.org/10.1136/jitc-2023-008094
Gandino IJ, Scolnik M, Bertiller E, Scaglioni V, Catoggio LJ, Soriano ER. Complement levels and risk of organ involvement in patients with systemic lupus erythematosus. Lupus Sci Med. 2017;4(1):e000209. https://doi.org/10.1136/lupus-2017-000209
Heeger PS, Lalli PN, Lin F, Valujskikh A, Liu J, Muqim N, et al. Decay‐accelerating factor modulates induction of T cell immunity. J Exp Med. 2005;201(10):1523–30. https://doi.org/10.1084/jem.20041967
京公网安备11010802044758号