Beta2-Microglobulin Can Be a Disease Activity Marker in Systemic Lupus Erythematosus

doi:10.1097/MAJ.0b013e3181d26dfb

The American Journal of the Medical Sciences

Volume 339, Issue 4, April 2010, Pages 337-340

https://doi.org/10.1097/MAJ.0b013e3181d26dfb Get rights and content

Abstract

Background

To investigate the clinical significance of beta2-microglobulin in Korean patients with systemic lupus erythematosus (SLE).

Methods

Blood samples were collected from patients with SLE (n = 100) and normal healthy controls (n = 50). The level of beta2-microglobulin was investigated by enzyme-linked immunosorbent assay. Serial samples from SLE patients were collected at 4.2 ± 2.6 months after first sampling.

Results

The beta2-microglobulin levels of the SLE patients (2.64 ± 0.11 μg/mL) were higher than the normal controls (2.14 ± 0.04 μg/mL, P < 0.001). The patients with SLE with serositis, oral ulcer, or lupus nephritis had significantly higher beta2-microglobulin levels than those without, respectively. A significant correlation was found between the beta2-microglobulin level and each of anti-dsDNA antibody, hemoglobin, complement, and SLE Disease Activity Index. In sequential sampling of patients with SLE, a positive correlation was found between the change of the SLE Disease Activity Index and the change of the beta2-microglobulin levels.

Conclusions

These data suggest that the measurement of beta2-microglobulin seem to be a useful addition to the laboratory tests that can help in assessment of disease activity of SLE.

Section snippets

MATERIALS AND METHODS

One hundred patients with SLE were enrolled. All met the revised criteria of the American College of Rheumatology for classification of SLE¹⁶ and were followed up at the Ajou University Hospital, and 50 healthy control subjects (NC) were recruited. Patients with impaired renal function, previous lymphoma, or multiple myeloma were excluded from the beta2-microglobulin analysis, as these conditions are known to be associated with increased serum beta2-microglobulin. All subjects gave their

RESULTS

The mean age was 32.8 ± 10.9 years (range, 13–62 years) in SLE patients and 29.5 ± 5.9 years in the NC. There are no significant differences in sex. However, the 2 groups significantly differed with age (P < 0.001). In SLE patients, 2 patients (2%) received cyclophosphamide pulse therapy, 7 patients (7%) were treated with azathioprine, and 3 patients (3%) were treated with cyclosporine. Daily glucocorticoids dose of SLE patients was 12.64 ± 17.21 mg prednisolone equivalent.

Serum beta2-microglobulin levels

DISCUSSION

To gain the clinical significance of beta2-microglobluin in the monitoring of SLE, we analyzed the level of beta2-microglobulin in SLE patients, relating them to disease activity and disease features. The beta2-microglobulin levels of the SLE patients were higher than the NC. The beta2-microglobulin levels were correlated with multiple clinical features and disease activity markers.

SLE is an autoimmune disorder characterized by several immunological changes, including B-cell hyperactivity and

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Cited by (35)

Serum beta2-microglobulin level in systemic lupus erythematosus patients: Relation to disease activity
2023, Egyptian Rheumatologist
Citation Excerpt :
In concordance, Gamal et al observed a significant correlation of β2M with both hematuria and pyuria [14]. Similarly, Kim et al. found that serum β2M was significantly higher in SLE patients with renal disease (hematuria and pyuria) [23]. Under normal conditions β2M is released by macrophages and lymphocytes, then it’sreabsorbed from proximal convoluted tubules after being filtered by renal glomeruli.
To assess the level of β2-microglubulin (β2M) in systemic lupus erythematosus (SLE) patients and its association with disease activity and other disease parameters.
40 SLE patients and 22 matched controls were studied. Serum β2M was assessed using enzyme-linked immunosorbent assay (ELISA). SLE Disease Activity Index (SLEDAI) and the damage index were assessed.
The patients were 36 females and 4 males (F:M 9:1) with a mean age of 28.5 ± 7.9 years and disease duration of 6.7 ± 3.3 years. The SLEDAI was 9.3 ± 5.2 and the damage index 1.83 ± 1.84. The mean level of serum β2M was significantly higher in SLE patients (6.42 ± 2.46 mg/L) than control (2.47 ± 0.4 mg/L) (p < 0.01).The serum level of β2M was significantly higher in patients with nephritis (n = 22) (7.45 ± 2.47 mg/L) compared to those without (n = 18) (5.17 ± 1.82 mg/L)(p = 0.002), And it was similar in those with and without arthritis (7.24 ± 2.3 mg/L vs 5.88 ± 2.4 mg/L (p0.07).The β2M significantly correlated with disease activity (r = 0.86, p 0.001), serum creatinine (r = 0.52, p > 0.001), urea (r = 0.63, p < 0.001), 24 h urinary protein (r = 0.56, p < 0.001), hematuria (r = 0.4, p < 0.01) and pyuria (r = 0.41; p < 0.01), ESR (r = 0.48; p < 0.01) and inversely with hemoglobin level (r = −0.34; p = 0.03). No significant correlation was found with C-reactive protein or with disease damage. Serum (β2M) significantly predicted nephritis and disease activity (sensitivity 63.6 %, specificity 77.8 %; p < 0.001 and 95 %CI: 0.25–0.41; p < 0.001 respectively).
Serum β2M is significantly associated with disease activity and lupus nephritis, suggesting that serum β2M may serve as a potential biomarker to monitor the disease activity and predicting lupus nephritis. However its association to disease severity needs further longitudinal studies.
Biomarkers of B cell activation in autoimmune connective tissue diseases: More than markers of disease activity
2022, Clinical Biochemistry
Citation Excerpt :
When both biomarkers were combined to evaluate the incidence of nephritis in SLE patients, the Area Under the Receiver Operating Characteristic (AUROC) curve was 0.927, which was significantly higher than anti-α-enolase antibodies or β2M alone [70]. Kim et al. and Tsai et al. similarly found that excretion of β2M in patients with LN was significantly higher than that in those without, however, Tsai et al. noted that excretion of β2M in patients with active or inactive LN was not significantly different [73,74]. Kim et al. also found that β2M in SLE patients with serositis or oral ulcers was significantly higher than in those without.
B cells play a central role in the pathogenesis of many autoimmune diseases, acting as antigen-presenting cells, producing inflammatory cytokines, and acting as a source of autoantibodies after differentiating into plasma cells. In this review, we aim to summarize and synthesize the literature for the utility of biomarkers of B cell activation (plasma immunoglobulins (Ig), free light chains (FLCs), and beta-2 microglobulin (β2M)) in monitoring inflammatory rheumatic connective tissue diseases, such as Sjogren’s syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc). Clinically, it is quite difficult to gauge prognosis in these conditions as there, historically, have not been many quantitative markers of disease activity available. From our extensive literature review, Ig, FLC, and β2M may function as invaluable prognostic markers of ongoing disease activity, and potentially as biomarkers for response to therapy or disease relapse. They are inexpensive and unsophisticated tests that are vastly underused in the setting of autoimmune disease. However, clinicians still need to be aware of the potential of false positives in times of infection or plasma cell dyscrasia, as these disease states can artificially increase these biomarkers. Ultimately, the utility of serum Ig, FLCs, and β2M is clearly delineated in SS and SLE, and least investigated in DM, and additional prospective studies utilizing these biomarkers, and specific B cell targeted therapies are still needed.
Elevated cerebrospinal fluid β2-microglobulin levels in patients with neuromyelitis optica spectrum disorders
2021, Multiple Sclerosis and Related Disorders
Cerebrospinal fluid (CSF) β2-microglobulin (β2-MG) levels elevated in patients with multiple sclerosis (MS). We examined the levels of β2-MG in serum and cerebrospinal fluid (CSF) from 46 patients with neuromyelitis optica spectrum disorders (NMOSD), in serum from 21 healthy controls (HC), in CSF from 25 disease controls with non-inflammatory neurological diseases (NIND) with normal CSF results. CSF β2-MG levels were significantly higher in patients with NMOSD than controls and with weak association with the number of white blood cells, protein and lactate levels in CSF. CSF β2-MG is thus one more, non-specific indicator of inflammation in NMOSD.
β2-microglobulin a biomarker of disease activity in systemic lupus erythematosus patients
2020, Revista Medica Clinica Las Condes
El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, caracterizada por daño crónico a órganos o sistemas, caracterizada por la activación anormal de linfocitos T y/o B debido a una presentación y reconocimiento antigénico anormal que favorece la producción de citoquinas pro inflamatorias y auto-anticuerpos fijadores de complemento que promueven la formación y depósito de complejos inmunes con el consecuente daño celular. También se caracteriza por periodos cíclicos de brote y remisión de la enfermedad. La búsqueda de biomarcadores clínicamente útiles para conocer de manera anticipada un brote de la enfermedad aún está en curso, entre los biomarcadores se sugiere que la β2-microglobulina (β2 M) puede ser útil para evaluar la actividad del LES.
El objetivo del estudio fue correlacionar la concentración de β2 M sérica con los marcadores comúnmente evaluados para establecer la actividad del LES.
La población de estudio consistió en 119 pacientes con LES activo y no activo (57 pacientes control, 42 pacientes con LES activo y 20 pacientes con LES inactivo) los cuales firmaron su consentimiento para participar en el estudio. El grupo control correspondía a pacientes sin antecedentes clínicos y familiares de enfermedad autoinmune. El grupo de pacientes con LES cumplía al menos 4 criterios de clasificación de LES del Colegio Americano de Reumatología. La concentración de β2 M se midió por ELISA. La actividad del LES fue evaluada mediante parámetros clínicos, niveles séricos de anti-ds-DNA, fracción del complemento C3 y C4. Los niveles de β2 M fueron asociados con marcadores serológicos de anti-nucleosoma, anti-C1q y creatinina.
El estudio reveló diferencia significativa en los niveles séricos de β2 M (p < 0.001) entre los tres grupos de estudio, en los pacientes con LES activo se observó una mediana 5,4 ug/mL, P₂₅ 3,17 ug/mL P₇₅ 6,72 ug/mL; el grupo control presentó una mediana menor al grupo LES activo de 1,8 ug/mL P₂₅ 1,6 ug/mL P₇₅ 1,9 ug/mL y al grupo de LES inactivo con mediana de 3,25 ug/mL P₂₅ 2,63 ug/mL P₇₅ 3,55 ug/mL. Además, se observó correlación de resultados entre la concentración de β2 M y niveles de anti-ds-DNA (p < 0,01; r = 0,595) y niveles séricos del complemento C3 (p < 0,01; r = −0,519) y C4 (p = 0,019; r = −0,345).
La medición de la β2 M sérica puede ser un biomarcador útil para evaluar la actividad de la enfermedad del LES siempre y cuando sea empleado con otros test de laboratorio que se utilizan de manera rutinaria para evaluar la actividad de LES.
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by chronic damage to organs or systems, due to abnormal activation of T and/or B-lymphocytes, caused by abnormal antigenic presentation and recognition that gives the production of pro- inflammatory cytokines and complement-fixing autoantibodies that promote formation of immune complexes and cellular damage. It is also characterized by cyclic periods of activation and remission. The search for clinically useful biomarkers for early knowledge of disease outbreak is going; biomarkers suggest that β2-microglobulin (β2 M) is useful for evaluating the activity of the SLE.
The objective of this study was to analyze the relationship between serum β2 M concentrations with markers of SLE activity.
One hundred nineteen patients were included (control 57, active SLE 42 and inactive SLE 20) who signed their consent to participate in the study. The control group corresponded to patients without clinical and family history of autoimmune disease. The patients group with SLE met at least four criteria of the American Society of Rheumatology for lupus diagnostic. β2 M concentration was measured using an ELISA test. SLE activity was evaluated by clinical parameters, serum levels of anti-ds-DNA, complement levels C3 and C4. β2 M levels were associated with anti-nucleosome, anti-C1q and creatinine.
The study revealed a significant difference between the three study groups (p < 0,01), in active SLE group a median 5,4 ug/mL, P25 3,17 ug/mL P75 6,72 ug/mL was observed. The control group presented a lower median to the active SLE group of 1,8 ug/mL P25 1,6 ug/mL P75 1,9 ug/mL and to the inactive SLE group with a median 3,25 ug/mL P25 2,63 ug/mL P75 3,55 ug/mL. In addition, correlation of results was observed between β2 M concentration and anti-ds-DNA levels (p < 0,01, r = 0,595) and complement serum level C3 (p < 0,01, r = -0,519) and C4 (p = 0,019; r = -0,345).
β2 M serum measurement can be a useful biomarker to assess the SLE activity as long as it is used with other laboratory tests that are routinely used to evaluate the activity of SLE.
Serum cystatin C and βeta-2 microglobulin as potential biomarkers in children with lupus nephritis
2023, Archives of Rheumatology
Serum beta-2 microglobulin as a predictor of nephritis, disease activity, and damage score in systemic lupus erythematosus: a cross-sectional study
2023, Rheumatology International

View all citing articles on Scopus

: This study was supported by the Brain Korea 21 project for Ajou University School of Medicine and by the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea grant A080588.

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Clinical InvestigationBeta2-Microglobulin Can Be a Disease Activity Marker in Systemic Lupus Erythematosus

Abstract

Background

Methods

Results

Conclusions

Section snippets

MATERIALS AND METHODS

RESULTS

DISCUSSION

Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function

Autoimmunity

Risk factors for infection and role of C-reactive protein in Korean patients with systemic lupus erythematosus

Clin Exp Rheumatol

Anti-DNA and autoantibodies

Curr Opin Rheumatol

Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus

Arthritis Rheum

Biomarkers in systemic lupus erythematosus: II. Markers of disease activity

Arthritis Rheum

Cytokines and their receptors as biomarkers of systemic lupus erythematosus

Expert Rev Mol Diagn

Studies on beta2-microglobulin in patients and normal subjects

Acta Clin Belg

Beta 2-microglobulin: its significance and clinical usefulness

Ann Clin Lab Sci

Beta-2 microglobulin—an immunogenetic marker of inflammatory and malignant origin

Ann Clin Lab Sci

Beta 2-microglobulin and its binding activity in serum from patients with SLE

Ann Rheum Dis

Beta 2-microglobulin levels in serum and urine of rheumatoid arthritis patients on gold therapy

Ann Rheum Dis

Clinical Investigation
Beta2-Microglobulin Can Be a Disease Activity Marker in Systemic Lupus Erythematosus