Regulation of β2-microglobulin expression in different human cell lines by proinflammatory cytokines

Vraetz, Thomas; Ittel, T. H.; Mackelenbergh, Michelle G. van; Heinrich, Peter C.; Sieberth, H. G.; Graeve, Lutz

doi:10.1093/ndt/14.9.2137

Cited by 44 publications

(30 citation statements)

References 39 publications

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“…6 Serum b 2 M indicates the clearance of middle molecules by HD, or may be related to inflammation, as suggested by some authorities. 22,23 Accumulation of b 2 M leads to dialysis-related amyloidosis, which usually becomes apparent after several years of HD. However, a postmortem study showed that b 2 M amyloid deposition occurs in 21% of cases within 2 years and in 33% within 4 years after initiation of HD.…”

Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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Increased prevalence of aortic and mitral valve calcification has been reported in patients on hemodialysis, but it remains unknown whether aortic and mitral valve calcification arise from similar pathogenesis. We detected heart valve calcification using two-dimensional echocardiography, and we related valve calcification to various clinical parameters in patients treated with hemodialysis three times a week for more than 1 year. In 112 patients (77 men and 35 women, age 67±10 years, duration on hemodialysis 95 ± 67 months), aortic and mitral valve calcification were observed in 84 (75.0%) and 58 (51.7%) patients, respectively. Aortic valve calcification was associated with increased age, higher serum calcium, lower serum albumin, lower total cholesterol and higher high-sensitivity C-reactive protein. Multivariate analysis showed that increased age and higher serum calcium were independently associated with aortic valve calcification. Conversely, mitral valve calcification was associated with increased age, higher high-sensitivity C-reactive protein and higher serum b 2 -microglobulin, but not with higher serum calcium. In multivariate analysis, increased age and higher serum b 2 -microglobulin were independently associated with mitral valve calcification. Serum b 2 -microglobulin was associated with longer duration on hemodialysis, malnutrition inflammation (lower serum albumin and higher high-sensitivity C-reactive protein) and dyslipidemia. Considering the results in previous studies showing that the distribution of b 2 -microglobulin amyloid deposition was consistent with that of tissue calcification in patients on hemodialysis, b 2 -microglobulin may have pathogenic roles in valve calcification.

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Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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“…7 A correlation between an inflammatory response during hemodialysis and elevated serum B2M has been already described. 8 Increased levels of B2M are seen in patients with hematologic and autoimmune disorders 9,10 but also seem to be elevated under conditions of high cell turnover, ischemia, or cardiomyopathy. 11,12 In 1 study in uremic patients on hemodialysis, B2M was related to carotid intima-media thickness.…”

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confidence: 99%

Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis

Amighi

Hoke²,

Mlekusch³

et al. 2011

Stroke

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Background and Purpose-Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events. Methods-One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. Results-We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (PϽ0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (PϽ0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better. Conclusions-B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis. (Stroke. 2011;42:1826-1833.)

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“…Taking into account that PCT is considered a marker of infection, [7][8][9]16,17,23] the correlation of B 2 -m to PCT is most likely attributed to the expression and production of these two substances from activated cells (i.e., monocytes, macrophages, lymphocytes). [5,17,24,25] This activation can be due to the secretion of cytokines and interferons during the immune response in the setting of pro-inflammatory substances release syndrome. Though this release can be provoked by infections or non-infectious conditions (e.g., contact of blood with bioincompatible membranes), the lack of correlation between B 2 -m to CRP, an accepted marker of systemic inflammatory reaction, [10][11][12] in all time periods points to the simultaneous production and release of B 2 -m and PCT only (or mostly) by infections.…”

Section: Discussionmentioning

confidence: 99%

Strong Correlation of B₂-Microglobulin (B₂-m) with Procalcitonin (PCT) in the Serum of Chronic Hemodialysis Patients: A Role for Infections in the Dialysis-Related Amyloidosis?

et al. 2008

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Introduction. Infections trigger the activation of defensive cells capable to produce and release B 2 -microglobulin (B 2 -m). Procalcitonin (PCT), secreted by a wide range of human cells, included the aforementioned defensive cells, is generally considered a sensitive and specific marker of infection. In this prospective study, we examined the possibility that infections, as detected by increased levels of PCT, increase the serum levels of B 2 -m in chronic hemodialysis (CHD) patients, possibly affecting the rate of progression of dialysis-related amyloidosis (DRA). Methods. For a period of four months, 76 CHD patients, 45 men/ 31 women, mean age 63 ± 15.7 years, with no residual renal function and in HD for 46 ± 50 months were studied bimonthly. Blood was drawn, at baseline T(0), two months T(2), and four months T(4), for measuring hematocrit (Ht), white blood cells (WBC), erythrocyte sedimentation rate (ESR), blood urea and serum creatinine, protein (albumin, globulin), C-reactive protein (CRP), and PCT και B 2 -m. Any events (especially infections) in the preceding 10-day period were recorded. Results. At baseline, 100% of all B 2 -m measurements were abnormal (>2.4 mg/ L), 13.4% of PCT values were increased (>1.5 ng/mL), and 49.4% of CRP values exceeded the lower limit of 5 mg/L with no statistically significant differences between the results of the three periods of the study. Statistically significant, in all periods, was the linear positive correlation of B 2 -m with PCT (T[0]: p < 0.001, T[2]: p < 0.004, T[4]: p < 0.001). Also, statistically significant (p < 0.005) was the positive correlation of B 2 -m to HD vintage. Conclusions. In this study, the strong positive correlation of B 2 -m to PCT probably signifies that the (mainly subclinical) infections increase B 2 -m production in CHD patients intensifying the problem of HD-related amyloidosis.

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Regulation of β2-microglobulin expression in different human cell lines by proinflammatory cytokines

Cited by 44 publications

References 39 publications

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis

Strong Correlation of B₂-Microglobulin (B₂-m) with Procalcitonin (PCT) in the Serum of Chronic Hemodialysis Patients: A Role for Infections in the Dialysis-Related Amyloidosis?

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Regulation of β2-microglobulin expression in different human cell lines by proinflammatory cytokines

Cited by 44 publications

References 39 publications

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis

Strong Correlation of B2-Microglobulin (B2-m) with Procalcitonin (PCT) in the Serum of Chronic Hemodialysis Patients: A Role for Infections in the Dialysis-Related Amyloidosis?

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Strong Correlation of B₂-Microglobulin (B₂-m) with Procalcitonin (PCT) in the Serum of Chronic Hemodialysis Patients: A Role for Infections in the Dialysis-Related Amyloidosis?