Volume 9, Number 3, September 2019
|Number of page(s)||6|
|Published online||27 August 2019|
Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity
Urmia University of Medical Sciences, Urmia, Iran
2 Shahid Beheshti University of Medical Sciences, Tehran, Iran
* Corresponding author. Department of Rheumatology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia. Iran. E-mail address: firstname.lastname@example.org (M. Aghdashi).
Accepted: 9 April 2019
Background: Designation of disease activity is serious for the management of systemic lupus erythematosus (SLE). Serum level of β2 microglobulin (β2M) may be associated with illness activity in SLE disease. Since the role of β2M for assessing of illness activity in SLE is not completely clear, the current study aimed to discern evaluation of β2M in patients with SLE and its correlation with sickness activity.
Materials and Methods: In this case-control study, 50 patients with SLE disease and 25 healthy individuals were selected in Imam Khomeini Hospital in central of Urmia.
Blood samples were collected safely from patients, serum was removed, and β2M measured using an ELISA method. The results for other parameters including C reactive protein, C3, C4, anti dsDNA and erythrocyte sedimentation rate were obtained from patients’ medical record. Data analyzed using appropriate statistical tests including Mann-Whitney U test, Independent f-test, Kruskal-Wallis, and Spearman used for analysis of data.
Results: In the current study, a significant difference was seen between two groups in terms of β2M (p < 0.001). Remarkable correlation was seen between the level of β2M with disease activity (p < 0.001). Furthermore, there are significant relevancy between the level of β2M with 24-hour urine protein, ESR, disease activity score, and CRP (p < 0.05).
Conclusion: The results revealed that serum amount of β2M in SLE patients is higher compared to healthy ones, which is significantly correlated to score of illness activity, CRP, and ESR in patients with SLE disease. Hence β2M might be an excellent serological marker helping the prediction of sickness activity and inflammation in SLE patients.
Key words: β2 microglobulin / Disease activity / SLE
© Author(s) 2019. This article is published with open access by China Medical University
Open Access This article is distributed under terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided original author(s) and source are credited.
Systemic lupus erythematosus (SLE) is a serologically and clinically heterogeneous illness  which leads to malfunction of the immune system [2–13]. It is a multiorgan disease stemmed from the production of a broad span of antinuclear antibodies and existence of immune complexes in the involved organs . Moreover, activation of T and B cells in SLE leads to the generation of autoantibodies and damage of tissues , evoking loss of self-tolerance. The tolerance loss following the deregulation of the immune system is due to genetic and environmental factors as well as stochastic events [15–18]. More than 30 genetic loci are involved in the pathogenesis of SLE .
According to previous study, the proper assessment of SLE activity and determination of its grade can identify suitable therapeutic regimes and manage the disease .
The current tools for estimation of disease activity are serum (anti-ds DNA) anti-double-stranded DNA antibodies, C3 and C4 complement components, and anti-C1q antibody [20–23]. CRP is a non-specific marker of various inflammatory situations, but it may be considered as a direct scale of disease or as a prognostic indicator of autoimmune diseases . Also, β2 microglobulin (β2M) is known as a low weight protein (11 kDa) existing in the all nucleated cell surfaces as section of main histocompatibility complex . Its daily formation is 50-200 mg with a plasma half-life of 2 hours . But it is proved that lymphocyte activity during lymphoproliferative and autoimmune illness can also alter the plasma level of β2M [25, 26]. The reabsorption of circulating β2M occurs in proximal renal tubule [27, 28] and the enhanced urinary β2M is a well-known sign of tubule interstitial renal diseases .
High amount of serum β2M have been reported in rheumatoid arthritis disease, Sjogren’s syndrome, and Systemic lupus erythematosus [29–31]. In addition, the level of β2M is as an index of illness activity for evaluating of SLE disease . However, the association of serum amount of β2M with SLE disease activity has not clearly elucidated yet. Since few studies have been done for evaluation of serum β2M level in patients with systemic lupus erythematosus and its correlation with disease activity in our country, the current study aimed to discern serum levels of β2M in SLE patients and its correlation with illness activity, CRP, and other parameters.
In current cross-sectional survey, 50 patients with diagnosed SLE disease from Imam Khomeini Hospital in central of Urmia, and 25 healthy individuals were included. All tests were performed in laboratory of Imam Khomeini Hospital. After giving consenting and approving of current study by Ethical Committee of University, demographic, clinical and other data of patients were obtained from medical records.
In this study, patients with definitive and deterministic diagnosis of SLE were selected, but the cases with concurring diabetes mellitus, endocrine disease, multiple myeloma, blood cancer and concomitant infection were excluded.
The score of SLE illness activity was calculated through the SLE- DAI or Systemic Lupus Erythematosus Disease Activity Index scoring guideline (SLEDAI 2000). Patients with SLE were classified into two subgroups of patients with score of less or more than 8.
A blood sample was collected via a safe vein puncture, and serum samples kept frozen at -20°C. β2M was measured using ELISA method (Pars Azmoon Co., Tehran, Iran)with a detection level of 0.1 mg/L. All steps were done according to the instructions.
CRP level was regularly evaluated for all patients during the first 24 hours. Nephlometery technique was used for assessment of human (Pars-Azmoon test kit, Tehran, Iran). All steps were done according to the instructions.
Erythrocyte sedimentation rate is a common hematologic test for the diagnosis of non-specific inflammation. When anticoagulant blood was transferred into the glass tube and placed immoble, the red blood cells dissipate from the plasma and precipitate. The speed at which red blood cells precipitate is measured as a transparent plasma millimeter appearing above the tube after an hour.
A Kinetic Nephelometric technique was used for assessment of Serum C3 and C4 using commercial kit (Pars Azmoon, Tehran, Iran). All steps were done according to the instructions.
The Farr assay (125I-labelled recombinant dsDNA) was used to determine serum anti-dsDNA antibodies according to manufacturer’s instruction (UK).
In current study, data were entered SPSS version 20. For comparison of case and control in terms of β2M and age, we used MannWhitney U test and Independent t test, respectively. For comparison of patients with respect to disease activity, Kruskal-Wallis was used. Spearman was applied for correlation of β2M with clinical data. P < 0.05 was considered for statistical analysis.
The mean value of clinical parameters of patients with SLE are summarized in Table 1.
The mean value of clinical data (ESR, Anti-ds DNA, C3, C4, Score of disease, duration of disease, age and 24 hour urine protein) in patients with SLE
No significant difference was organized between age of case (32.01 ± 1.61) and control (30.28 ± 1.11) groups (p = 0.37).
Table 2 presentes the status of CRP in patients with SLE.
- Frequency distribution of CRP in patients with SLE.
As clear from table 2, only 6% of patients with SLE had CRP score +3.
Table 3 shows comparison of serum levels of β2M in patients with SLE and control.
Comparison of serum levels of β2M in patients with SLE and control group.
As shown in table 3, a significant difference was seen in serum levels of β2M in SLE patients with healthy subjects (p < 0.001).
Table 4 summarized β2M level in SLE patients and subjects of control.
The comparison of serum amount of β2 microglobulin in SLE patients and healthy subject.
As domonestrated in Table 4, remarkable difference in serum levels of β2M was found between healthy subjects and patients with active and inactive SLE (p < 0.001).
Table 5 showed the correlation of β2M with duration of disease, SLEDAI, ESR level, CRP, anti-ds DNA, C4, C3 and 24 urine protein in SLE patients.
The correlation of β2 Mwith duration of disease, SLEDAI, ESR level, CRP, anti-ds DNA, C4, C3 and 24 urine protein in SLE patients.
Significant relevancy was seen between the serum amount of β2M with age, a score of disease activity, ESR, CRP and 24-hour urine protein (p < 0.05) (Table 5). However, no significant correlation was observed with C3 and C4, duration of disease, anti dsDNA (p > 0.05).
Fig. 1 shows correlation between serum β2M with score activity disease in patients with SLE.
Correlation of Serum Β2M with score activity disease in SLE patients.
Spearman coefficient correlation was used for correlation of serum β2M with score activity disease in patients with SLE and reported 0.39.
SLE as an autoimmune disease is associated with many immunological changes such as T cell abnormality and B cell hyperactivity. Recently, the significance of β2M for assessing of SLE activity has been highlighted.
In current study, significant relevancy was seen between case and control groups in terms of β2M, so that lower level of β2M was detected in healthy control compared to SLE patients. Kim et al., in similar study evaluated the level of β2M through ELISA in normal healthy one and patients with SLE disease  and reported that theses patients have higher level of β2M than healthy control. Yeung et al., measured the amount of serum β2M in 115 patients with SLE  and observed increased level of serum β2M in 16.4% of patients with external manifestation of SLE . Iwona et al., conducted a study on 100 SLE patients and observed increased level of β2M in 97% of them . Hermansen et al., also demonstrated that the concentration of β2M was remarkably higher in SLE patients . The reason of elevated amount of β2M in SLE disease has not been completely clear. Such an increase might be due to turnover of lymphocytes during lympho proliferative and autoimmune illness [35–38] or presence of immune complexes (β2M and anti-β2M antibodies) which is elemi- nated by kidney . But, Wakabayashi et al., showed that β2M level was decreased during the immunosuppressive treatment .
Furthermore, we observed remarkable correlation between disease activity and serum level of β2M in SLE patients Moreover, Choe Y et al., achieved similar result and reported that the level of β2M is accompanied with disease activity in women with SLE . Kim et al., showed that the level of serum β2M can be as an excellent biomarker for determining of disease activity in patients with SLE . Lwona et al., reported that increased level of β2M is correlated with disease activity including SLEDAI . Hermansen et al., demonstrated significant correlation between SLEDAI score and β2M . Choe et al., evaluated urine β2M and SLEDAI in patients with SLE and reported that there was significant association between urine SLEDAI and β2M .
In another study, the level of β2M was assumed for distinguishing of disease activity . According to findings of aforementioned studies, it seems that β2M can be assumed as a good parameter for detecting SLE activity .
In current study, remarkable relevancy was observed between serum β2M and 24 hour urine protein. Choe et al., also observed a relevancy between renal involvement and disease activity in SLE didease . Badr et al, reported that β2M is an accurate and sensitive marker for evaluating of renal action. They also reported that there is significant relation between β2M and glomerular filtration rate (GFR) .
Moreover, we observed a significant relevancy between serum level of β2M with CRP and ESR. Skare et al., evaluated the correlation between serum level of β2M and ESR. They found a positive correlation between SLEDAI and ESR which is consistent with our study . Rezaeiyazdi et al., observed higher level of CRP in patients with lupus disease compared to healthy control. But they reported that this marker could not be as a good indicator for disease activity . Enocsson et al., evaluated serum level of CRP in 155 SLE patients and 100 controls. They saw a powerful relevancy between the level of CRP and disease activity. They also reported that CRP genotype affects the response of CRP in patients with SLE. Therefore, it seems that polymorphisms in the CRP gene can influence CRP answer in these patients .
Furthermore, no significant relevancy was seen between serum level of β2M with anti-dsDNA antibodies and C3, as well as C4in current study. However, Żychowska et al., observed the correlation between the level of β2M with complement of C4, C3 and anti-dsDNA  which is inconsistent with our study. It seems that one of the possible reasons is due to methods used for measurement of these biomarkers. In Żychowska’ s study, C4 components were measured by turbidimetry method, and antidsDNA antibody was evaluated by ELISA technique, while in our study, the 125I Farr assay and nephelometric technique were used for assessment of anti-dsDNA and C4, respectively. Moreover, different kits used in various studies is other influential factor on results and findings. In addition, sample size of Żychowska’s study was greater than our study.
Skare et al. evaluated the level of β2M and C3 in systematic lupus disease and reported a inverse relevancy between the level of β2M and C3 . We also observed inverse relevancy between β2M and C3, but this correlation was not statistically emi- ment which could be due to our smaller sample size than Skare et al., study. In addion, current study did not achive significant correlation between C4 component and β2M, while Lewona et al., observed significant association between C4 component and β2M . Maybe it is due to small sample size. We assessed this study on 50 patients, wherease, Lewona et al., performed this study on larger sample size.
According to data of current study, serum level of β2M is increased in SLE patients which is correlated to score of activity of disease, CRP and ESR. It seems that β2M may be a favorable biomarker and excellent serological marker in laboratory tests to assess disease activity of SLE.
The authors wish to disclose no conflicts of interest.
We thanks of staff of Imam Khomeini Hospital, Urmai, Iran.
- Hermansen M-LF, Hummelshø L, Lundsgaard D, Hornum L, Keller P. Increased serum β2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosuspatients. Lupus. 2012; 21: 1098–104. [CrossRef] [PubMed] [Google Scholar]
- Kim H, Jeon J, Jeong-Moon Y. Beta2-Microglobulin Can Be a Disease Activity Marker in Systemic Lupus Erythematosus. AJMS. 2010; 339(4): 337–40. [CrossRef] [Google Scholar]
- Kyttaris VC, Krishnan S, Tsokos GC. Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function. Autoimmunity. 2006; 39: 705–9. [CrossRef] [PubMed] [Google Scholar]
- Badr Abeer M, El-Melligy Dalal Mohamed, Mostafa Heba, El Deeb Somaya. 1 Evaluation of Beta2-Microglobulin as a Possible Biomarker for Assessment of Disease Activity in Systemic Lupus Erythematosus and Chronic Kidney Disease. World J Med Sci. 2005; 12(1): 26–35. [Google Scholar]
- Kanne JP, Yandow DR, Haemel AK, Meyer CA. Beyond Skin deep: thoracic manifestations of systemic disorders affecting the skin. Radiographics. 2011; 31: 1651–68. [CrossRef] [PubMed] [Google Scholar]
- Midgly A. Systemic Lupus Erythematosus (SLE). Category: Immune Dysfunction. British Society for Immunology. Bitsized Immunology. 2018. [Google Scholar]
- Hochberg MC, Boyd RE, Ahearn JM, Arnett FC, Bias WB, Provost TT, et al. Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on demographic subsets. Medicine (Baltimore). 1985; 64(5): 285–95. [CrossRef] [PubMed] [Google Scholar]
- Davies K, Bukhari M, Ottewell L. Acroosteolysis in a patient with systemic lupus erythematosus/mixed connective tissue disease. Rheumatology (Oxford). 2018; 12: 1–8. [Google Scholar]
- Mira-Avendano IC, Abril A. Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed connective tissue disease. Rheum Dis Clin North Am. 2015; 41(2): 263–77. [CrossRef] [PubMed] [Google Scholar]
- Williams JN, Chang SC, Sinnette C, Malspeis S, Parks CG, Karlson EW, et al. Pesticide exposure and risk of systemic lupus erythematosus in an urban population of predominantly African-American women. Lupus. 2018; 27(13): 2129–34. [CrossRef] [PubMed] [Google Scholar]
- Ho Ch. Lupus Erythematosus, Drug-Induced. StatPearls Internet. Treasure Island (FL): StatPearls. 2018; 1–8. [Google Scholar]
- Vedove CD, Del Giglio M, Schena D, Girolomoni G. Drug-induced lupus erythematosus. Arch Dermatol Res. 2009; 301(1): 99–105. [CrossRef] [PubMed] [Google Scholar]
- Chlebus E, Wolska H, Blaszczyk M, Jablonska S. Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus: diagnostic criteria and therapeutic implications. J Am Acad Dermatol. 1998; 38(3): 405–12. [CrossRef] [PubMed] [Google Scholar]
- Tony E, Mohammed H, Fathi N, Tonys Abeer A, Afifi Ola, Abdou Madleen Adel A, Gamal Rania M. Serum and Urinary Biomarkers, Endothelin-1, Beta-2 Microglobulin, Cystatin C, Galectin-3 and Alpha-1-acid Glycoprotein; Can they Surrogate Clinical and Histological Staging in Lupus Nephritis Patients?. J Arthritis. 2016; 5: 6–9. [Google Scholar]
- Choi J. The Pathogenesis of Systemic Lupus Erythematosus – An Update. Curr Opin Immunol. 2012; 24(6): 651–7. [CrossRef] [PubMed] [Google Scholar]
- Delgado-Vega. Recent findings on genetics of systemic autoimmune diseases. Curr Opin Immunol. 2010; 22: 698–705. [CrossRef] [PubMed] [Google Scholar]
- Deng Y, Tsao BP. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol. 2010; 6: 683–92. [CrossRef] [PubMed] [Google Scholar]
- Taylor KE, Chung SA, Graham RR, Ortmann WA, Lee AT, Langefeld CD, et al. Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes. PLoS Genet. 2011; 7: e1001311. [CrossRef] [PubMed] [Google Scholar]
- Skare T. Systemic lupus erythematosus activity and beta two microglobulin levels. Sao Paulo Med J. 2014; 132(4): 239–42. [CrossRef] [PubMed] [Google Scholar]
- Gladman DD, Ibenz D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002; 29: 288–91. [PubMed] [Google Scholar]
- Gordon C, Sutcliffe N, Skan J, Stoll T, Isenberg DA. Definition and treatment lupus flares measured by the BILAG index. Rheumatology. 2003; 42: 1372–9. [CrossRef] [PubMed] [Google Scholar]
- Trendelenburg M. Antibodies against C1q in patients with systemic lupus erythematosus. Semin Immunopathol. 2005; 27: 276–85. [Google Scholar]
- Żychowska I, Suszek D, Dryglewska M, Majdan M. β2-micro- globulin as a marker of systemic lupus erythematosus activity. Adv Clin Exp Med. 2018; 27(3): 379–82. [CrossRef] [PubMed] [Google Scholar]
- Wibell LB. Studies on beta2-microglobulin in patients and normal subjects. Acta Clin Belg. 1976; 31: 14–26. [Google Scholar]
- Choe Y. Urine β2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus. SAGE J. 2014; 8: 1–10. [Google Scholar]
- Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity. 2010; 33: 967–78. [CrossRef] [PubMed] [Google Scholar]
- Bronson PG, Chaivorapol C, Ortmann W, Behrens TW, Graham RR. The genetics of type I interferon in systemic lupus erythematosus. Curr Opin Immunol. 2012; 1–9. [Google Scholar]
- Craft JE. Dissecting the immune cell mayhem that drives lupus pathogenesis. Sci Transl Med. 2011; 3: 73–9. [Google Scholar]
- Evrin PE, Strom T. Beta 2-microglobulin and its binding activity in serum from patients with SLE. Ann Rheum Dis. 1984; 43: 267–74. [CrossRef] [PubMed] [Google Scholar]
- Latt D, Weiss JB, Jayson MI. Beta 2-microglobulin levels in serum and urine of rheumatoid arthritis patients on gold therapy. Ann Rheum Dis. 1981; 40: 157–60. [CrossRef] [PubMed] [Google Scholar]
- Strom T, Evrin PE, Karlsson A. Serum beta-2-microglobulin in Sjogren’s syndrome. Scand J Rheumatol. 1978; 7: 97–100. [CrossRef] [PubMed] [Google Scholar]
- Yeung CK, Wong KL, Wong WS, Chan KH. beta 2-Microglobulin and systemic lupus erythematosus. J Rheumatol. 1986; 13(6): 1053–8. [PubMed] [Google Scholar]
- Żychowska Iwona. β2-microglobulin as a marker of systemic lupus erythematosus activity. Advances in Clinical and Experimental Medicine. Adv Clin Exp Med. 2018; 27(3): 379–82. [CrossRef] [PubMed] [Google Scholar]
- Hermansen ML, Hummelshøj L, Lundsgaard D, Hornum L, Keller P, Fleckner J, et al. Increased serum β2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients. Lupus. 2012; 21(10): 1098–104. [CrossRef] [PubMed] [Google Scholar]
- Font J. Serum beta 2-microglobulin as a marker of activity in systemic lupus erythematosus. Scand J Rheumatol. 1986; 15(2): 201–5. [CrossRef] [PubMed] [Google Scholar]
- Maury CP, Helve T, Sjoblom C. Serum beta 2-microglobulin, sialic acid, and C-reactive protein in systemic lupus erythematosus. Rheumatol Int. 1982; 2: 145–9. [CrossRef] [PubMed] [Google Scholar]
- Curry R, Thoen J, Shelborne C, Gaudernack G, Messner R. Antibodies to and elevations of beta 2 microglobulin in the serum of ankylosing spondylitis patients. Arthritis Rheum. 1982; 25: 375–80. [CrossRef] [PubMed] [Google Scholar]
- Karlsson FA, Wibell L, Evrin PE. Beta 2-microglobulin in clinical medicine. Scand J Clin Lab Invest Suppl. 1980; 154: 27–37. [PubMed] [Google Scholar]
- Wakabayashi K, Inokuma S, Matsubara E, Onishi K, Asashima H, Nakachi S, et al. Serum β2-microglobulin level is a useful indicator of disease activity and hemophagocytic syndrome complication in systemic lupus erythematosus and adultonset Still’s disease. Clin Rheumatol. 2013; 32: 999–1005. [Google Scholar]
- Rezaeiyazddi Z. Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus? SAGE Journal. 2011; 3: 1–5. [Google Scholar]
- Enocsson H, Sjöwall C, Kastbom A, Skogh T, Eloranta ML, Rönnblom L, et al. Association of serum C-reactive protein levels with lupus disease activity in the absence of measurable interferon-a and a C-reactive protein gene variant. Arthritis Rheumatol. 2014; 66(6): 1568–73. [CrossRef] [PubMed] [Google Scholar]
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