Serum Levels of Beta-2 Microglobulin in Rheumatoid Arthritis Patients and its Relationship with Disease Activity: Can it be used as a Disease Activity Marker?

Abstract

Background Beta-2 microglobulin (β2M) is mainly released from activated lymphocytes. Increased serum β2M levels have been shown in autoimmune diseases. The aim of this study was to analyse the serum levels of β2M in rheumatoid arthritis (RA) patients and to evaluate its relationship with disease activity measures.

Material and Methods This cross-sectional study included 137 RA patients, 102 ankylosing spondylitis patients (AS) and 50 healthy controls (HC). To assess the disease activity of RA patients, the 28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR), the 28-joint Disease Activity Score-C-Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were used. A p value of <0.05 was considered statistically significant.

Results Serum β2M levels were significantly higher in RA patients (2.95±1.19 mg/L) compared with HC (2.21±0.54 mg/L) and AS patients (2.200.58 mg/L) (p<0.001). There was a statistically significant correlation between β2M levels and DAS28-ESR (rs=0.359, p<0.001), DAS28-CRP (rs=0.293, p=0.001), SDAI (rs=0.332, p<0.001) and CDAI (rs=0.291, p=0.001). Serum β2M levels were higher in the RA group with DAS28-ESR ≥3.2 (3.30±1.42 mg/L) than in the DAS28-ESR <3.2 group (2.67±0.87 mg/L) (p=0.002).

Conclusion Our study revealed that serum β2M levels were higher in RA patients than in healthy controls, and, in contrast to other studies, we found positive correlations between β2M levels and RA disease activity measures.

Zusammenfassung

Hintergrund Beta-2-Mikroglobulin (β2M) wird hauptsächlich aus aktivierten Lymphozyten freigesetzt. Erhöhte Serumlevel von β2M wurden bei Autoimmunerkrankungen nachgewiesen. Ziel dieser Studie war es, die Serum β2M-Level bei Patienten mit rheumatoider Arthritis (RA) zu analysieren und ihren Zusammenhang mit Messungen der Krankheitsaktivität zu bewerten.

Material-Methoden Diese Querschnittsstudie umfasste 137 RA, 102 Patienten mit Morbus Bechterew (MB) und 50 gesunde Kontrollen (GK). Zur Beurteilung der Krankheitsaktivität von RA-Patienten wurden 28 Gelenkaktivitäts-Score Blutsenkungsgeschwindigkeit (DAS28-BSG), 28 Gelenkaktivitäts-Score C-reaktives Protein (DAS28-CRP), vereinfachter Krankheitsaktivitätsindex (SDAI) und klinischer Krankheitsaktivitätsindex (CDAI) verwendet. Ein p-Wert von <0,05 wurde als statistisch signifikant angenommen.

Ergebnisse Die Serum β2M Konzentrationen waren bei RA-Patienten (2,95±1,19 mg/L) signifikant höher als bei GK (2,21±0,54 mg/L) und Spondylitis ankylosans (AS)-Patienten (2,20±0,58 mg/L) (p<0,001). Es bestand eine statistisch signifikante Korrelation zwischen den β2M Werten und DAS28-BSG (rs=0,359, p<0,001), DAS28-CRP (rs=0,293, p=0,001), SDAI (rs=0,332, p<0,001), CDAI (rs=0,291, p=0,001). Die Serum β2M-Levels waren in der RA-Gruppe mit DAS28-ESR≥3.2 (3,30±1,42 mg/L) höher als in der DAS28-ESR<3,2-Gruppe (2,67±0,87 mg/L) (p=0,002).

Diskussion Unsere Studie zeigte, dass die Serum β2M-Levels bei der RA höher als bei gesunden Kontrollen waren. Außerdem fanden wir positive Korrelationen zwischen den β2M-Levels und den Aktivitätswerten der RA im Gegensatz zu anderen Studien.

Key words

beta 2 microglobulin - rheumatoid arthritis - ankylosing spondylitis

Schlüsselwörter

Beta-2-Mikroglobulin - Rheumatoide Arthritis - Spondylitis ankylosans

Publication History

Article published online:
19 November 2020

• References

• 1 Mateen S, Zafar A, Moin S. et al. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Sinoviyal membran Clinica Chimica Acta 2016; 455: 161-171
• 2 Brzustewicz E, Bryl E. The role of cytokines in the pathogenesis of rheumatoid arthritis- practical nd potential application of cytokines as biomarker and target of personalized therapy. Cytokine 2015; 76: 527-536
• 3 Latt D, Weiss BJ, Jayson MIV. Β2-microglobulin levels in serum and urine of rheumatoid arthritis patients on gold therapy. Ann Rheum Dis 1981; 40: 157-160
• 4 Aygündüz M, Bavbek N. Öztürk. et al. Serum beta 2-microglobulin reflects disease activity in Behçet’s disease. Rheumatol Int 2002; 22: 5-8
• 5 Ribaudo RK, Margulies DH. Independent and synergistic effects of disulfide bond formation, beta-2 microglobulin and peptides on class1 MHC folding and assembly in an in vitro translation system. J Immunol. 1192. 149-2935-2944
• 6 Li L, Dong M, Wang X-G. The implication and significance of beta 2 microglobulin: A conservative multifunctional regulator. Chinese Medical Journal 2016; 129: 448-455
• 7 Bethea M, Forman DT. Beta-2 Microglobulin- An immunogenetic marker of inflammatory and malignant origin. Annals of Clinical and Laboratory Science 1982; 12: 447-452
• 8 Leffers HCB, Hermansen ML, Sandholt B. et al. Plasma levels of β2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study. Lupus. 2018; 27: 1517-1523
• 9 Kim HA, Jeon JY, Yoon JM. et al. Beta2-microglobulin can be a disease activity marker in systemic lupus erythematosus. American Journal of Medical Sciences 2010; 339: 337-340
• 10 Wibell LB. β2-microglobulin in patients and normal subjects. Acta Clinica Belgica 1976; 31 (suppl8) 14-26
• 11 Evrin PE, Strom T. Beta 2-microglobulin and its binding activity in serum from patients with SLE. Ann Rheum Dis 1984; 43: 267-274
• 12 Strom T, Evrin PE, Karlsson A. Serum beta 2-microlgobulin in Sjögren’s syndrome. Scand J Rheumatol 1978; 7: 97-100
• 13 Zissis M, Afraoudakis A, Galanopoulos G. et al. B2 microglobulin: Is it a reliable marker of activity in inflammatory bowel disease?. The American Journal of Gastroenterology 2001; 7: 247-68.
• 14 Aletaha D, Neogi T, Silman AJ. et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62: 2569-2581
• 15 Van der Linden S, Vanlkenburg HA, Cats A. Evaluation of Diagnostic criteria for Ankylosing Spondylitis. A proposal for modification of the New York Criteria. Arthritis Rheum 1985; 27: 361-368
• 16 van Gestel AM, Prevoo ML, van't Hof MA. et al. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996; 39: 34-40
• 17 Aletaha D, Nell VP, Stamm T. et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 2005; 7: R796-R806
• 18 Smolen JS, Breedveld FC, Schiff MH. et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford) 2003; 42: 244-257
• 19 Garret S, Jenkinson T, Kennedy LG. et al. A new approach to defining disease status in ankylosing spondylitis. The Bath Ankylosing spondylitis disease activity index. J Rheumatol 1994; 21: 2286-2291
• 20 Calin A, Garret S, Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994; 21: 2281-2285
• 21 Lukas C, Landewé R, Sieper J. et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68: 18-24
• 22 Berggard I, Bearn AG. Isolation and properties of a low molecular weight β2-globulin occuring in human biological fluids. J Biol Chem 1968; 243: 4095-4103
• 23 You L, Xie R, Haijuan H. et al. High levels of serum β-2microglobulin predict severity of coronary artery disease. BMC Cardiovascular Disorders 2017; 17: 71
• 24 Aghdashi M, Salami S, Nezhadisalami A. Evaluation of the serum β2 microglobulin level in patients with systemic lupus erthematosus and its correlation with disease activity. BioMedicine 2019; 9: 6-11
• 25 Zychowska I, Suszek D, Dryglewska M. et al. Β2-microglobulin as a marker of systemic lupus erythematosus activity. Adv Clin Exp Med 2018; 27: 379-382
• 26 Gottenberg JE, Seror R, Miceli-Richard C. et al. Serum levels of beta-2 microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren’s syndrome. Data at enrollment in the prospective ASSESS Cohort. PLoS ONE 2013; 8: e59868
• 27 Riega-Torres J, Delgado- Garcia G, Salas-Alanis JC. et al. Beta-2 microglobulin in whole unstimulated saliva can effectivrly distinguish between sjögren’s syndrome and non-autoimmune Sicca symptoms. Arch Rheumatol 2017; 32: 284-289
• 28 Talal N, Grey HM, Zivaifler N. et al. Elevated salivary and sinovial fluid B2-microglobulin in Sjögren’s syndrom and rheumatoid arthritis. Scince 1975; 187: 1196-1198
• 29 Manicort D, Brauman H, Orloff S. Plasma and urinary levels of β2 microglobulin in rheumatoid arthritis. Ann Rheum Dis 1978; 37: 328-332
• 30 Sjöblom KG, SAxne T, Wollheim FA. Plasma levels of β2-microglobulin in rheumatoid arthritis. Ann Rheum Dis 1980; 39: 333-339
• 31 Walters MT, Stevenson FK, Goswami R. et al. Comparison of serum and synovil fluid concentrations of β2-microglobulin and C reactive protein in relation to clinical disease activity and synovial inflammation in rheumatoid arthritis. Ann Rheum Dis 1989; 48: 905-911
• 32 Shi C, Zhu Y, Su Y. et al. Beta-2 microglobulin: Emerging as a promising cancer therapeutic target. Drug Discov Today 2009; 14: 25-30
• 33 Balint E, Sprague SM. Beta (2)-microglobulin and bone cell metabolism. Nephrol Dial Transplant 2001; 16: 1108-1111
• 34 Tsai CY, Wu TH, Yu CL. et al. Increased excretions of beta2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron 200 85: 207-214
• 35 Olsen N, Sokka T, Seehorn CL. et al. A gene expression signature for recent onset rheumatoid arthritis in peripheral blood mononuclear cells. Ann. Rheum. Dis. 2004; 63: 1387-1392
• 36 Mavragani CP, La DT, Stohl W. et al. Association of the response to tumor necrosis factor antagonists with plasma type I interferon activity and interferon-beta/alpha ratios in rheumatoid arthritis patients: a post hoc analysis of a predominantly Hispanic cohort. Arthritis Rheum 2010; 62: 392-401
• 37 Wendling D, Mas J, Chatelain F. et al. Serum beta 2-microglobulin and ankylosing spondylitis. Rev Rhum Mal OSteoartic 1989; 56: 441-443
• 38 Kepekçi Y, Boğa C, Başlamışlı F. et al. Ankilozan Spondilitli olgularda serum beta-2 microglobulin düzeyleri ve hastalık aktivitesi ilişkisi. Gaziantep Üniversitesi Tıp Fakültesi Dergisi 1992; 3: 155-161
• 39 Beersma MF, Derhaag PJ, Feltkamp TE. Serum levels of beta 2-miroglobulin in HLA-B27+ patients with acute anterior uveitis and ankylosing spondylitis. Scand J Rheumatol Suppl 1990; 87: 104-107