β 2-microglobulin as a marker of systemic lupus erythematosus activity

Material and methods. The study group consisted of 69 SLE patients (62 women and 7 men), aged 34.5 ±11 years (19–69). Patients with kidney failure and infection were excluded from the study group. The concentration of β2M was measured using an ELISA test. SLE activity was assessed with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and by measuring the levels of C3 and C4 complement components, anti-double stranded DNA antibodies (anti-dsDNA antibodies) and β2M. The relationship between β2M and the clinical manifestation of SLE was also covered in the study.


Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease leading to chronic inflammation of numerous tissues and organs.The pathogenesis of SLE is complex and associated, i.a., with excessive activation of T and B cells, apoptosis impairment, and inadequate immune complex clearance.Excessive B cell activation results in the overproduction of autoantibodies, which combine with chromatin, creating immune complexes and inducing inflammation. 1][7] The search for new SLE activity markers is ongoing.In recent years, the effectiveness of marking the β2-microglobulin (β2M) serum concentrations in monitoring SLE activity has been consistently highlighted.β2M is a lowmolecular-weight protein found on the surface of nucleated cells, including lymphocytes and macrophages.As a result of T and B cells activation, β2M is released, resulting in the elevation of its serum concentration level.The increased concentration of the protein is found chiefly in patients suffering from lymphoproliferative diseases, kidney failure and autoimmune diseases. 8,9[12][13]

Patients and methods
The study was carried out on a group of 69 SLE patients (62 women and 7 men) aged 34.5 ±11 years (19-69), hospitalized at the Department of Rheumatology and Connective Tissue Diseases of the Medical University of Lublin between 2013 and 2014.All patients met the 1997 SLE diagnosis criteria of the American College of Rheumatology.The average disease duration was 5.8 ±4.8 years (0.5-19).Mucocutaneous symptoms were found in 22 patients (31.9%), arthritis in 7 patients (10.1%), 8 patients (11.6%) were diagnosed with lupus nephritis, hematological symptoms were found in 6 patients (8.7%), and vasculitis in 8 patients (11.6%).None of the patients were diagnosed with nervous system disorder or serositis.Patients suffering from infection, cancer and kidney failure were excluded from the study group.
In all the patients, SLE activity was assessed through checking the concentration of C3 and C4 components, anti-dsDNA antibodies and β2M, as well as using SLEDAI-2K.β2M serum concentration was measured using an ELISA test.C3 and C4 components levels were measured by turbidimetry, and anti-dsDNA antibodies concentration was determined by ELISA.
The statistical analysis was done using STATISTICA v. 10.0 software (StatSoft, Kraków, Poland).All data was given as means ±SD.Nonparametric tests were used: the Mann-Whitney U test and Spearman's rank correlation coefficient.Differences were considered significant at p < 0.05.

Results
Table 1 shows the selected parameters of disease activity assessment in the group of SLE patients.The study group revealed a statistically significant correlation between β2M concentration and anti-dsDNA antibodies titer (p < 0.05; r = 0.3), C4 component (p < 0.05; r = −0.3),and SLEDAI-2K (p < 0.05; r = 0.6) (Fig. 1-3).No significant relationship was found between β2M and C3 component, the patients' age or the duration of the disease.
Table 2 presents mean concentrations of β2M in SLE patients with different clinical manifestations of the disease.β2M concentration was significantly higher in patients with No statistically significant deviation of β2M concentration was found in patients suffering from cutaneous and/or mucosal manifestations or kidney damage (Table 2).

Discussion
Considerable importance has been attached recently to early detection of SLE exacerbation and to monitoring its activity.The search for sensitive markers of the disease activity continues to enable anticipation of exacerbation at the preclinical stage.The significance of β2M in monitoring SLE activity has been highlighted lately.This study revealed that increased β2M level was found in 34.8% of the patients, and correlated with the disease activity markers such as SLEDAI-2K, anti-dsDNA antibodies titer, and C4 component.Considerably higher β2MG levels were found in patients with musculoskeletal system involvement, hematological symptoms and vasculitis.
The study by Kim et al., conducted on 100 SLE patients, revealed increased β2M concentration in 97% of patients.β2M concentration was significantly higher in patients with serositis, oral erosions and symptoms of lupus nephritis.Much like in the case of the study described in the present paper, a statistically significant correlation was found between β2M and anti-dsDNA antibodies titer, C3 component and hemoglobin concentration, and SLE-DAI disease activity score. 10Hermansen et al. examined 26 SLE patients and proved the relationship between β2M concentration and disease activity scored according to SLEDAI, C3 complement component and daily proteinuria.They also found a significant correlation between the concentration of β2M and cytokines responsible for SLE pathogenesis: IL-6, IL-8, IL-10, IL-18, IFN-α. 11Similar results were obtained by Skare et al. -in a group of 129 SLE patients, β2M concentration correlated with SLEDAI, OB, anti-dsDNA antibodies, and C3. 12 Wakabayashi et al. proved that β2M concentration decreased throughout the course of immunosuppressive treatment. 13he cause of elevated β2M concentration in SLE patients is not fully understood.Some researchers suggest the β2M increase may result from increased lymphocyte turnover in autoimmune disease, or the presence of immune complexes formed by β2M with anti-β2M antibodies removed by kidneys. 10,14,15An experimental study on diseased SLE mice with β2M deficiency revealed differences in the clinical picture of the disease -a higher percentage of mice with cutaneous symptoms, with a lower percentage of kidney damage.The results suggest a possible influence of β2M on the clinical course of SLE. 16e number of studies assessing the significance of β2M in monitoring SLE activity is scarce.So far, only a small group of patients has been studied, with very few studies focused on the influence of treatment on β2M concentration.The authors consider it viable to include β2M in the process of assessing SLE activity, and to monitor β2M concentration in the same patients over different disease activity periods.

Table 1 .
Selected markers of disease activity in SLE patients