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The Journal of Biological Chemistry Apr 2015β2-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare form of... (Review)
Review
β2-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare form of familial systemic amyloidosis. These two types of amyloidoses differ significantly in terms of the tissue localization of deposits and for major pathological features. Considering how the amyloidogenesis of the β2-microglobulin mechanism has been scrutinized in depth for the last three decades, the comparative analysis of molecular and pathological properties of wild type β2-microglobulin and of the D76N variant offers a unique opportunity to critically reconsider the current understanding of the relation between the protein's structural properties and its pathologic behavior.
Topics: Amyloid; Amyloidosis; Doxycycline; Humans; Models, Molecular; Mutation; Protein Aggregation, Pathological; Protein Conformation; Renal Dialysis; Single-Chain Antibodies; beta 2-Microglobulin
PubMed: 25750126
DOI: 10.1074/jbc.R115.639799 -
Journal of Dairy Science Feb 1982beta 2-Microglobulin has been isolated from several species, but only bovine beta 2-microglobulin, previously known as lactollin, has been crystallized. An improved... (Comparative Study)
Comparative Study Review
beta 2-Microglobulin has been isolated from several species, but only bovine beta 2-microglobulin, previously known as lactollin, has been crystallized. An improved method for its isolation from colostrum is described. The bovine homologue exhibits a concentration-dependent aggregation behavior. beta 2-Microglobulin is related to both immune and histocompatibility antigen systems. It exhibits homology with the constant domains of the immunoglobulin-G light and heavy chains and is an integral part of histocompatibility antigens bound to cell surface. beta 2-Microglobulin also occurs in the free state in various body fluids including milk and colostrum. The possible relationship of elevated free beta 2-microglobulin of pathological conditions is suggested for future research.
Topics: Amino Acid Sequence; Animals; Beta-Globulins; Cattle; Colostrum; HLA Antigens; Histocompatibility Antigens; Humans; Milk; beta 2-Microglobulin
PubMed: 6176605
DOI: 10.3168/jds.S0022-0302(82)82193-0 -
Proceedings of the National Academy of... Aug 1979beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized...
beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized as a precursor with an NH2-terminal extension of 19 amino acids: Ser-X-Ser-Val-X-Leu-Val-Phe-Leu-Val-Leu-Val-Ser-Leu-X-Gly-Leu-Tyr-X. The processing and segregation of this peripheral membrane protein are directly comparable to those of secretory proteins and integral membrane proteins: addition of dog pancreas microsomal membranes during translation caused conversion to the processed chain, but addition of membranes after synthesis did not; only the processed chain sedimented with the membrane vesicles and was protected from proteolysis by the vesicles; and processing of nascent beta 2-microglobulin was blocked by competitive inhibitors that prevent processing and segregation of secretory and integral membrane proteins. These results suggest that the signal sequences of secretory proteins, integral membrane proteins, and peripheral membrane proteins have a common function and a common receptor on the cytoplasmic face of dog pancreas microsomal membranes. This system also provides a means for studying in vitro the expression and function of the major histocompatibility antigens that are associated with beta 2-microglobulin on cell surfaces.
Topics: Amino Acid Sequence; Animals; Beta-Globulins; Binding Sites; Cell Line; Cell-Free System; Membrane Proteins; Mice; Microsomes; Protein Biosynthesis; Protein Precursors; Reticulocytes; beta 2-Microglobulin
PubMed: 91168
DOI: 10.1073/pnas.76.8.3651 -
Chinese Medical Journal Feb 2016This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate. (Review)
Review
OBJECTIVE
This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.
DATA SOURCES
The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.
STUDY SELECTIONS
Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.
RESULTS
β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.
CONCLUSIONS
Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.
Topics: Antigens, CD1; Hemochromatosis Protein; Histocompatibility Antigens Class I; Humans; Receptors, Fc; beta 2-Microglobulin
PubMed: 26879019
DOI: 10.4103/0366-6999.176084 -
Journal of the American Society For... Jul 2021NMR studies and X-ray crystallography have shown that the structures of the 99-residue amyloidogenic protein β-microglobulin (βm) and its more aggregation-prone...
NMR studies and X-ray crystallography have shown that the structures of the 99-residue amyloidogenic protein β-microglobulin (βm) and its more aggregation-prone variant, D76N, are indistinguishable, and hence, the reason for the striking difference in their aggregation propensities remains elusive. Here, we have employed two protein footprinting methods, hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP), in conjunction with ion mobility-mass spectrometry, to probe the differences in conformational dynamics of the two proteins. Using HDX-MS, a clear difference in HDX protection is observed between these two proteins in the E-F loop (residues 70-77) which contains the D76N substitution, with a significantly higher deuterium uptake being observed in the variant protein. Conversely, following FPOP-MS only minimal differences in the level of oxidation between the two proteins are observed in the E-F loop region, suggesting only modest side-chain movements in that area. Together the HDX-MS and FPOP-MS data suggest that a tangible perturbation to the hydrogen-bonding network in the E-F loop has taken place in the D76N variant and furthermore illustrate the benefit of using multiple complementary footprinting methods to address subtle, but possibly biologically important, differences between highly similar proteins.
Topics: Amino Acid Substitution; Humans; Hydrogen Deuterium Exchange-Mass Spectrometry; Protein Conformation; Protein Footprinting; beta 2-Microglobulin
PubMed: 33586970
DOI: 10.1021/jasms.0c00438 -
Blood Research Sep 2014Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its... (Review)
Review
Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its potential role as a convenient and non-invasive prognostic indicator in malignant lymphomas, the influence of serum β2 microglobulin is currently underestimated, and therapeutic decision making is rarely affected by this marker. Recent studies that included relatively large numbers of patients with specific histologic subtypes showed that serum β2 microglobulin is a potent prognostic marker in malignant lymphomas. In follicular lymphoma, this effort led to the incorporation of serum β2 microglobulin as an indicator in a new prognostic model. In this review, we summarize the current evidence supporting the role of serum β2 microglobulin as a prognostic factor in patients with malignant lymphoma and discuss perspectives for future investigations.
PubMed: 25325033
DOI: 10.5045/br.2014.49.3.148 -
Acta Obstetricia Et Gynecologica... 2007An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e.g. beta-trace protein,...
BACKGROUND
An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e.g. beta-trace protein, beta-2-microglobulin and cystatin C, are increased in the third trimester of normal pregnancy. The plasma levels of cystatin C and beta-2-microglobulin are further increased in pre-eclampsia, and the cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of beta-trace protein, beta-2-microglobulin and cystatin C in pre-eclampsia, and to determine the diagnostic performance of these proteins compared to that of urate and creatinine.
METHODS
A case-control study of 57 women diagnosed with pre-eclampsia, and 218 healthy women with uncomplicated singleton pregnancies in the third trimester. Women in the catchment area of Lund, Sweden, were included during an 18-month period from October 2003 to April 2005. Venous blood samples were drawn upon inclusion when diagnosis was made. The maternal plasma concentrations of the 3 proteins were analysed by automated particle-enhanced immunoturbidimetric assays.
RESULTS
The plasma levels of the 3 proteins were significantly higher in the third trimester of pre-eclamptic patients compared to healthy pregnant women in the third trimester. The upper reference limits (parametric 97.5 percentile) were 2.57 mg/l for beta-2-microglobulin, 0.72 mg/l for beta-trace protein and 1.37 mg/l for cystatin C. ROC analysis showed similar diagnostic performance for the 3 proteins, with beta-trace protein displaying the best diagnostic performance of all the analytes.
CONCLUSIONS
In this study, the maternal plasma levels of beta2-microglobulin, beta-trace protein and cystatin C were all significantly elevated in pre-eclampsia compared to those of healthy pregnant women, and displayed similar diagnostic performance for diagnosing pre-eclampsia. The results indicate that low molecular mass proteins are useful as markers of renal impairment in pre-eclampsia.
Topics: Adult; Biomarkers; Blood Proteins; Case-Control Studies; Cystatin C; Cystatins; Female; Humans; Intramolecular Oxidoreductases; Lipocalins; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; ROC Curve; beta 2-Microglobulin
PubMed: 17653875
DOI: 10.1080/00016340701318133 -
Postepy Dermatologii I Alergologii Oct 2020Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. Prognostic factors may help to evaluate the course of the disease and may also be...
INTRODUCTION
Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. Prognostic factors may help to evaluate the course of the disease and may also be useful in selecting appropriate treatment plans for patients.
AIM
To investigate the potential prognostic factors of MF and their correlations with MF stage.
MATERIAL AND METHODS
We evaluated the records of patients with MF who were followed in our lymphoma clinic between 1998 and 2015. Age, sex, disease stage, peripheral blood eosinophilia, eosinophil cationic protein, serum total IgE, lactate dehydrogenase (LDH), and β-microglobulin levels were investigated and recorded at the time of diagnosis.
RESULTS
There was a statistically significant positive correlation between high β-microglobulin levels and the advanced stage of disease ( < 0.001). The older group of patients had statistically significantly higher levels of β-microglobulin compared to the younger group ( = 0.001). We found strong, significantly positive correlations between disease stage and β-microglobulin, LDH, and total IgE levels ( < 0.001, rho = 0.335; = 0.001, = 0.302; = 0.001, = 0.311, respectively). Additionally, there were significantly positive correlations between LDH levels and β-microglobulin, total IgE levels ( < 0.001, rho = 0.484; = 0.001, = 0.212, respectively). Study limitations: A limited number of patients and the retrospective nature of the study.
CONCLUSIONS
We found that β-microglobulin was a significant prognostic factor in our study population of MF patients. Also, elevated LDH, β-microglobulin, and total IgE levels were correlated with advanced disease. Thus, these parameters can be used together to identify patients who have progressed to the later stages of the disease and who require more aggressive treatment.
PubMed: 33240023
DOI: 10.5114/ada.2020.100491 -
Kidney International Oct 2004Daily short hemodialysis (HD) is often prescribed by simply doubling treatment frequency and halving treatment time; however, the effect of this prescription approach on...
BACKGROUND
Daily short hemodialysis (HD) is often prescribed by simply doubling treatment frequency and halving treatment time; however, the effect of this prescription approach on the equilibrated HD dose (urea eKt/V) and whole body clearance for beta(2)-microglobulin has not been established.
METHODS
We compared urea and beta(2)-microglobulin kinetics during and 60 minutes after a short HD treatment and a conventional HD treatment in a crossover study on 22 maintenance HD patients: 16 male and 6 female, 61 +/- 18 (mean +/- standard deviation) years of age. One patient in each treatment modality was excluded from certain analyses because of missing data. Short and conventional HD treatments were essentially identical, except for treatment times, which were 116 +/- 14 and 241 +/- 27 minutes, respectively. Blood samples were collected at regular intervals during and after treatments, and additional blood and dialysate samples were collected at 60 minutes of treatment to evaluate dialyzer clearances.
RESULTS
Plasma water urea clearances measured directly across the dialyzer during short and conventional HD treatments were not different (255 +/- 23 mL/min and 255 +/- 28 mL/min, respectively). The 60-minute postdialysis blood urea nitrogen concentration rebounded more (P < 0.01) after short HD than conventional HD (5.9 +/- 3.1 vs. 4.0 +/- 1.5 mg/dL, respectively). Calculated urea eKt/V values using the Daugirdas-Schneditz rate equation were not different from those measured during conventional HD using the 60-minute postdialysis concentration but significantly overestimated measured urea eKt/V values during short HD. Postdialysis rebound of beta(2)-microglobulin concentrations was variable but similar after short and conventional HD treatments (0.1 +/- 3.4 vs. 0.7 +/- 1.8 mg/L, respectively). Whole body clearances of beta(2)-microglobulin calculated from predialysis and immediate (10-second) postdialysis serum concentrations during short and conventional HD treatments were not different from each other (42.9 +/- 24.1 vs. 41.9 +/- 22.4 mL/min, respectively).
CONCLUSION
These observations show that the Daugirdas-Schneditz rate equation is accurate in predicting urea eKt/V during conventional, but not during short, HD. In contrast, whole body clearances of beta(2)-microglobulin during short and conventional HD treatments were similar. We conclude that calculation of accurate estimates of urea eKt/V, but not clearances of beta(2)-microglobulin, differ during short and conventional HD treatments.
Topics: Blood Urea Nitrogen; Humans; Kidney Failure, Chronic; Kinetics; Models, Biological; Renal Dialysis; Urea; Water; beta 2-Microglobulin
PubMed: 15458465
DOI: 10.1111/j.1523-1755.2004.00934.x -
Antimicrobial Agents and Chemotherapy Oct 1987The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in...
The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and beta 2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group. Overall, beta 2M elimination was variable in all treatment groups. Although the beta 2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminopeptidases; CD13 Antigens; Female; Gentamicins; Humans; Male; Middle Aged; Vancomycin; beta 2-Microglobulin
PubMed: 2893584
DOI: 10.1128/AAC.31.10.1461