Serum Myeloperoxidase Level in Systemic Lupus Erythematosus

Ming-jian Bai, Jing Feng, Feng Yu, Cun-ling Yan, Chan-juan Cui, Lei Huang, and Zhen-ru Feng*

1Department of Clinical Laboratory, Aerospace Central Hospital, Beijing 100049, China

2Department of Nephrology,3Department of Clinical Laboratory, Peking University First Hospital, Beijing100034, China

Serum Myeloperoxidase Level in Systemic Lupus Erythematosus

Ming-jian Bai1, Jing Feng1, Feng Yu2, Cun-ling Yan3, Chan-juan Cui3, Lei Huang3, and Zhen-ru Feng3*

1Department of Clinical Laboratory, Aerospace Central Hospital, Beijing 100049, China

2Department of Nephrology,3Department of Clinical Laboratory, Peking University First Hospital, Beijing100034, China

myeloperoxidase; systemic lupus erythematosus

Chin Med Sci J 2015; 30(3):199-202

SYSTEMIC lupus erythematosus (SLE) is a systemic autoimmune disease. Several mechanisms have been put forward as underlying the loss of self-tolerance and development of organ dysfunction, such as genetic, environmental, hormonal and immunoregulatory factors.1In recent years, oxidative stress is considered as an important factor in the atherogenesis of SLE.2Morgen et al3illustrated elevated levels of protein oxidation in serum from patients with SLE, which may play a role in the pathogenesis of chronic organ damage in SLE.

Myeloperoxidase (MPO), a member of the human peroxidase family, is a heme enzyme stored in and released by activated polymorphonuclear neutrophils (PMNs).4,5In the past, experiments of MPO mainly focused on its microbicida capacity;6however, in recent years, major investigations of MPO have been shifted to its non-microbicidal inflammatory processes. For instance, high level of serum MPO has been associated with atherosclerosis,7chronic kidney disease,8and activated ulcerative colitis.9

A few studies have investigated the role of serum MPO level in autoimmune disease. For example, MPO is elevated in patients with rheumatoid arthritis.10However, serum MPO level in SLE is still in controversy. Decreased serum MPO level was noted in one study in patients with SLE compared with controls and a trend toward decreased MPO level with increasing disease activity.3In contrast, another study showed that patients with SLE presented increased serum MPO level compared with controls, but there was no correlation between plasma MPO level and disease activity,11suggesting that MPO may play a role in the inflammatory process of some SLE manifestations.

The purpose of the present study is to determine the serum MPO level in SLE patients, and the possible correlation between MPO level and disease activity of SLE.

PATIENTS AND METHODS

Participants

A total of 196 out-patients with SLE were consecutively enrolled in this study between August 2012 and March 2014 from the Department of Nephrology of Peking University First Hospital. All the patients fulfilled the American College of Rheumatology (ACR) revised criteria for the classificationof SLE.12Patients with other autoimmune diseases, infectious disease, diabetes mellitus, leukemia, and malignancy were excluded. Meanwhile, 121 healthy controls were recruited from the Regular Physical Examination Center of Peking University First Hospital during the same period, with the same exclusion criteria as the SLE group. All the participants signed informed consent, and the study was approved by the Ethic Committee of Peking University First Hospital.

Disease activity assessment

Disease activity was assessed based on the SLE Disease Activity Index (SLEDAI) score.13Neutrophils, complement 3 (C3), complement 4 (C4), anti-dsDNA antibody were all detected at the time of enrollment into the present study. All the SLE patients were allocated into two groups according to SLEDAI score, Group I (n=73) with inactive disease (SLEDAI=0-4) and Group II (n=123) with active disease (SLEDAI≥5). Group II were further divided into 3 subgroups: the mild active group (SLEDAI=5-9, n=66), the moderate active group (SLEDAI=10-14, n=34) and the severe active group (SLEDAI≥15, n=23). The SLEDAI score of all SLE patients was assessed by a rheumatologist of Peking University First Hospital.

Laboratory indicator measurement

The peripheral blood was collected into serum tube and centrifuged at 3000 rpm for 10 minutes. Serum was cryopreserved in refrigerator at –80°C. MPO was quantified with a commercial ELISA kit (American RB company) according to the manufacturer’s instructions, the values were expressed as U/L. Anti-MPO antibody was tested with a commercial ELISA kit (EUROIMMUN Medical Laboratory Diagnostics Stock Company, Germany) according to the manufacturer’s instructions, the values were expressed as RU/ml. Avalue≥20 RU/ml was considered as a positive result. Neutrophils were measured by LH-750 (Beckman-Coulter, America). C3 and C4 were detected by rate nephelometry (IMMAGE 800, Beckman-Coulter, America). Anti-dsDNA antibody was detected using a commercial ELISA kit (EUROIMMUN Medical Laboratory Diagnostics Stock Company).

Statistical analysis

Statistical analysis was performed with SPSS version 13.0. The Kolmogorov-Smirnov test showed that all data presented as non-normally distribution, all results were expressed as median and interquartile range (IR). Mann-Whitney U test was used for comparison of quantitative variables between SLE patients and healthy controls, and Kruskal-Wallis test was used for comparison of quantitative variables among the 3 active subgroups. Chi-square test was used for comparison of rates in different groups. Spearman rank correlation test was used to evaluate correlation between serum MPO level and SLEDAI score. Two-sided P values less than 0.05 were considered statistically significant.

RESULTS

The median age of SLE patients and healthy controls were 34 (27-45) and 32 (28-45) years, respectively, with no significant difference (P=0.828). The median course of disease in the SLE patients was 36 (12-108) months. The median serum MPO level in the SLE patients was 305.55 (138.33-591.85) U/L, significantly higher than that in the healthy controls [202.93 (148.04-298.78) U/L, P=0.001, Table 1].

The neutrophils and serum MPO between Group I and Group II were not significantly different; C3, C4 and anti-dsDNA antibody between the 2 groups were significantly different (Table 2). The serum MPO level in the three subgroups of Group II were 291.43 (153.40-583.52), 305.55 (146.84-614.98) and 438.37 (160.75-677.01), respectively, without significant difference (P=0.465).

There was no correlation between serum MPO level and SLEDAI score in SLE patients (r=0.130, P=0.069); serum C3, C4 and anti-dsDNA antibody levels were all correlated with SLEDAI score (r=–0.465, P=0.001; r=–0.356, P=0.001; r=0.329, P=0.001). There was significant correlation between serum MPO level and neutrophils (r=0.462, P=0.001).

Patients with neuropsychiatric involvement had higher serum MPO level than patients without (P=0.044); patients with arthritis involvement had lower serum MPO level than patients without (P=0.033). Patients with or without nephritis (P=0.189), mucocutaneous manifestations (P=0.072) and hematologic abnormalities involvements (P=0.331) had no significant difference in serum MPO levels.

DISCUSSION

Previous research findings regarding the MPO level in SLE patients are controversial, the inconsistency may be due to small sample size. The result of the present study showed higher serum MPO level in SLE patients compared with healthy controls.

MPO act on its substrate hydrogen peroxide and generates a number of reactive oxygen species with documented cytotoxic properties, such as hypochlorous acidwhich can contribute to host tissue damage.14Recent studies have demonstrated that MPO is an important factor in the initiation and progression of various inflammatory diseases.15

Table 1. Demographic features and laboratory results of the SLE patients and the controls

Table 2. Laboratory values of the Group I and Group II of SLE patients

Ren et al16found that increased peripheral blood cell apoptosis is correlated with increased disease activity of SLE, which suggested that the release of intracellular enzymes, including MPO and MPO products, by apoptotic neutrophils could be responsible for tissue damage of SLE. Combined with the results of the present study (serum MPO level of SLE patients was higher than healthy controls), we suggest that MPO may play a role in the pathogenesis of SLE. In the present study, 10 of the 196 SLE patients presented anti-MPO antibody, previous research17also found similar results, however, we found no difference in anti-MPO antibody between SLE patients and healthycontrols.

This study found no correlation between serum MPO level and disease activity of SLE, and no significant difference in MPO level was observed between active and inactive patients, consistent with Telles et al’s result.11On the contrary, the levels of serum C3, C4, and anti-dsDNA antibody were all significantly correlated with disease activity of SLE, which had been considered biomarkers in evaluating disease activity of SLE for a long time.13We concluded that, compared with C3, C4 and anti-dsDNA antibody, serum MPO may not help in evaluating the disease activity of SLE.

In this study, we found out that the serum MPO level of SLE patients with neuropsychiatric involvement was higher than patients without. On the contrary, patients with arthritis involvement had lower MPO level compared with patients without. With no clear explanation, we speculate that patients with different organ involvement may have different serum MPO levels.

In conclusion, serum MPO level in SLE patients is higher than that in healthy controls. MPO may play a role in the pathogenesis of SLE. There is no correlation between serum MPO level and disease activity of SLE, indicating that MPO level could not reflect the disease activity of SLE. Patients with different organ involvement may have different serum MPO level.

Acknowledgements

We acknowledge the support by Department of Nephrology, Peking University First Hospital.

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Received for publication December 9, 2014.

*Corresponding author Tel: 86-10-83575545/2042, E-mail: fengzhenru@ sina.com