REVIEW ARTICLE Serum/plasma homocysteine levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis Napoleon Bellua Sam 1,2 & Qin Zhang 1,2 & Bao-Zhu Li 1,2 & Xiao-Mei Li 3 & De-Guang Wang 4 & Hai-Feng Pan 1,2 & Dong-Qing Ye 1,2 Received: 6 December 2019 /Revised: 17 January 2020 /Accepted: 7 February 2020 # International League of Associations for Rheumatology (ILAR) 2020 Abstract Published studies have shown contradictory results in the association of serum/plasma levels of homocysteine (HCY) with systemic lupus erythematosus (SLE). This study is to systematically evaluate the association of serum/plasma HCY levels in SLE. A search was done using PubMed, Embase, Web of Science, and ScienceDirect databases up to 7 April 2019. Thirty-six articles including 2919 SLE patients and 3120 healthy controls were finally included in this meta-analysis. The HCY levels were significantly higher in SLE patients than in healthy controls (P < 0.001). The subgroup analysis revealed that Asian, African, Arab, Mixed, White and others as well as ages (<35 and ≥ 35) had significant higher HCY levels in SLE patients than in the healthy controls. The study indicated that patients with disease activity index scores < 8 (P < 0.001) and ≥ 8(P = 0.003) of SLE had significant higher HCY levels as compared with the healthy controls. It was also revealed that disease duration in SLE patients for < 10 and ≥ 10 years (P < 0.001) had significant higher HCY levels as compared with the healthy controls. A significant higher HCY level for body mass index (< 23 and ≥ 23) was found as well as measurement type in SLE patients than healthy controls. This meta-analysis demonstrated higher HCY levels in patients with SLE than healthy controls, suggesting a possible role of HCY in the disease. Key Points • Homocysteine (HCY) is closely related to the mechanisms of systemic lupus erythematosus (SLE). • This study reveals a significant correlation between HCY levels and the various indexes of disease activity. • This study reveals that medication may influence HCY levels in SLE. • This study also discovers that the subgroup analysis of all the factors influences the HCY levels in SLE patients. Keywords Healthy controls . Homocysteine . Matched population . Meta-analysis . Systemic lupus erythematosus Introduction The systemic lupus erythematosus (SLE) is a prototypic auto- immune disease that has a wide collection of clinical expres- sions. It affects all ethnic, gender, and age groups with over 90% SLE cases being women within childbearing age. SLE patients have multiple arrays of irregularities involving their immune systems. The genetic component of SLE patients is complex and made up of several genes that convert different molecules with vital roles in the modification of the immune system [1–4]. Twin and genetically related studies recom- mended that heredity did play a function in lupus development [5]. A lot of biological as well as chemical studies have shown irregularities in the role of T and B cells, apoptosis, complex immune clearance, complement function and deficiencies, and nucleosome processing [6, 7]. Generally, such studies support an abnormal operational immune system. What really Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10067-020-04985-w) contains supplementary material, which is available to authorized users. * Hai-Feng Pan panhaifeng@ahmu.edu.cn; panhaifeng1982@sina.com * Dong-Qing Ye ydqahmu@126.com; ydq@ahmu.edu.cn 1 Department of Epidemiology & Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China 2 Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China 3 Department of Rheumatology and Immunology, Anhui Provincial Hospital, 17 Lujiang Road, Hefei, Anhui, China 4 Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, Anhui, China Clinical Rheumatology https://doi.org/10.1007/s10067-020-04985-w