Serum Beta 2-microglobulin Concentrations Research Articles

Association of Beta-2 Microglobulin with Stroke and All-Cause Mortality in Adults Aged ≥40 in U.S.: NHANES III.

Stroke is the predominant cause of death worldwide. We aimed to investigate the association of serum beta-2 microglobulin ( 2M) concentrations with risk of stroke and all-cause mortalities in a cohort study. Overall, 4914 U.S. adults (mean age = 63.0 years, 44.3% male) were recruited from the National Health and Nutrition Examination Survey (NHANES Ⅲ). During a median follow-up of 19.4 years, 254 stroke deaths and 3415 all-cause deaths were identified by the National Center for Health Statistics. The associations of 2M with stroke and all-cause mortalities were investigated by using weighted Cox proportional hazard regression models. 2M was positively associated with stroke and all-cause mortality in unadjusted models and multivariable-adjusted models. The multivariable HR (95% CI) for stroke mortality in Q5 VS Q1 of serum 2M concentrations was 3.45 (1.33-8.91; p for trend = 0.001) and that for all-cause mortality was 3.95 (3.05-5.12; p for trend 0.001). In subgroup analyses, the association of 2M and stroke mortality did not vary by different levels of sociodemographic and general stroke risk factors (p interaction 0.05). In addition, the magnitude of positive association between 2M with all-cause mortality did vary by age, ratio of family income to poverty, smoking status, and history of hypertensive (p interaction 0.05). Our findings suggest that support that 2M may be a marker of stroke and all-cause mortality, which provides a new perspective for the study of cerebrovascular health and long-term survival in the future.

Evaluation of serum interleukin 2 receptor and beta-2-microglobulin as prognostic factors for canine lymphoma: A pilot study.

Interleukin 2 receptor (IL-2R) is released from activated T cell lymphocytes and related to proliferation of B cells and T cells. Beta-2-microglobulin (B2M) is synthesized from all nucleated cells and constitutes a major histocompatibility complex class I antigen. In human medicine, high concentrations of these two factors have been found to be related to prognosis in aggressive non-Hodgkin's lymphoma. In this pilot study, we aimed to assess the correlation between the serum concentration of IL-2R and B2M and the diagnosis and prognosis of canine lymphoma. This study included 8 healthy dogs and 17 dogs with lymphoma. To measure the serum concentration of IL-2R and B2M, a commercial enzyme-linked immunosorbent assay was used. In dogs with lymphoma, IL-2R concentrations were significantly high at the time of diagnosis, but B2M concentrations were not. In relapsed dogs, both IL-2R and B2M concentrations were significantly higher than those in the control and chemotherapy response groups. When the serum concentrations of IL-2R and B2M during chemotherapy were monitored in four relapsed dogs, B2M levels were more closely related with relapse. This study demonstrated that serum IL-2R and B2M concentration can be a diagnostic or prognostic tool for canine lymphoma. Monitoring of serum B2M concentration seems to be useful for predicting relapse.

Association of Beta-2-Microglobulin With Coronary Heart Disease and All-Cause Mortality in the United States General Population.

Few prospective studies explored the association of beta-2-microglobulin (B2M) with coronary heart disease (CHD) mortality. The primary objective of this study was to examine the association of serum B2M with CHD and all-cause mortality. This is a prospective cohort study of a nationally representative sample of 4,885 adults, aged 40–85 years, who participated in the National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994. The relationships between B2M and CHD and all-cause mortality were estimated using Cox proportional hazards regression models. During a median follow-up of 15.5 years, 845 CHD and 3,388 all-cause deaths occurred among 4,885 participants [2,568 women (55.7%); mean (S.D.) age, 66.4 (12.5) years], respectively. In the unadjusted model, B2M concentration was strongly linearly associated with CHD and all-cause mortality (p-trend < 0.001). After adjusting multivariable factors, a positive linear association between B2M and all-cause mortality was still observed (H.R. for Q4 vs. Q1 5.90; 95% CI: 5.31–6.57; p-trend < 0.001). In the multivariable adjustment model, B2M was significantly associated with an increased risk of CHD mortality (H.R. for Q4 vs. Q1 2.72; 95% CI: 2.07–3.57; p-trend < 0.001). In the stratified analyses, the associations of B2M with CHD and all-cause mortality varied by risk factors, such as age, smoking status, and history of hypertension. The findings suggest a significant relationship between the higher serum B2M concentration and increased risk for CHD and all-cause mortality. Further large-scale follow-up studies are also needed to validate this association.

Predicting 3-year mortality based on the tumor necrosis factor alpha concentration in low-flux hemodialysis patients.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients.

The prognostic values of beta-2 microglobulin for risks of cardiovascular events and mortality in the elderly patients with isolated systolic hypertension.

Background:The present study aimed to investigate the effects of serum beta-2 microglobulin (B2M) on the risks of major cardiovascular events (MACEs) and all-cause death in Chinese elderly isolated systolic hypertension (ISH) patients without severe renal insufficiency (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2).Materials and Methods:Serum B2M concentration, creatinine-eGFR, and blood pressure variability were evaluated in 460 elderly patients (mean age, 82.6 years; 28 women) with ISH in this observational study. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios (HRs) of risk factors for cardiovascular events and all-cause deaths.Results:During a median follow-up period of 37.6 months, 63 patients (13.7%) died, and 65 patients (14.1%) had MACEs. Multivariable analysis showed that the higher serum B2M concentration (B2M ≥0.28 mg/dl) was an independent predictor of increased risk of MACEs (nonfatal acute myocardial infarction, acute heart failure, ischemic stroke, and cardiovascular deaths) and all-cause death (HR: 2.62, 95% confidence interval [CI]: 1.46–4.69, P = 0.001 and HR: 3.40, 95% CI: 1.78–6.48, P < 0.001, respectively) adjusting for other multiple confounders including creatinine-eGFR and cystatin C. In addition, blood pressure variability derived from ambulatory blood pressure measurement was not associated with incidence of MACEs and all-cause mortality (P > 0.05).Conclusion:Our data suggest that serum B2M concentration may be individually associated with MACEs and all-cause death in elderly ISH patients without severe renal insufficiency even after adjusted for creatinine-eGFR and cystatin C.

Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients

Recently, serum beta2-microglobulin, an endogenous marker for renal function, has been shown to be an independent predictor of mortality in older adults. However, the prognostic role of beta2-microglobulin in heart failure has not been elucidated. We prospectively evaluated serum beta2-microglobulin and creatinine concentrations, creatinine-based renal parameters (estimated glomerular filtration rate and creatinine clearance), and echocardiographic data in 131 patients with acute heart failure and creatinine concentrations < or =3.0mg/dL admitted to our hospitals. During 2.3+/-1.3 years, 42 patients died of cardiovascular causes and 12 died of noncardiac causes. Cardiovascular events were observed in 63 patients: 53 were readmitted due to worsening heart failure, 5 readmitted for cerebral embolism, and 5 died from sudden cardiac death. According to multivariate stepwise Cox proportional hazard analysis, higher baseline serum beta2-microglobulin concentrations (X(2)=16, p<0.0001), previous congestive heart failure (X(2)=11, p<0.001), presence of chronic obstructive pulmonary disease (X(2)=8, p<0.01), and lower diastolic blood pressure (X(2)=6, p<0.05) were independent predictors of increased cardiovascular events. Also, higher baseline serum beta2-microglobulin (X(2)=20, p<0.0001), lower systolic blood pressure (X(2)=11, p<0.001), higher relative left ventricular wall thickness (X(2)=6, p<0.05), and lower body mass index (X(2)=5, p<0.05) were independent predictors of increased cardiac mortality. The adjusted hazard ratio for cardiovascular events increased with baseline serum beta2-microglobulin above 2.1 mg/L: 2.9 with beta2-microglobulin of 2.2-2.6 mg/L (95%CI 1.2-6.9, p<0.05), 2.9 with beta2-microglobulin of 2.7-3.9 mg/L (95%CI 1.2-7.2, p<0.05), and 4.7 with beta2-microglobulin of > or =4.0 mg/L (95%CI 2.0-11, p<0.001). Higher baseline serum beta2-microglobulin concentration could be a promising risk marker in acute heart failure patients with creatinine < or =3.0 mg/dL.

Elevated serum FGF23 concentrations in plasma cell dyscrasias

Fibroblast growth factor 23 (FGF23) is now recognized as a key regulator of phosphate metabolism. Numerous reports have found elevated serum FGF23 concentrations in oncogenic osteomalacia associated with mesenchymal tumors. Hypophosphatemic osteomalacia more rarely occurs in non-mesenchymal tumors. We identified elevated serum FGF23 levels in one patient with chronic lymphatic leukemia (CLL) and hypophosphatemia, prompting us to examine FGF23 concentrations in other patients with B-cell neoplasms. FGF23 levels were elevated in several patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), and were significantly associated with serum paraprotein and beta-2 microglobulin concentrations in these patients. Hypophosphatemia was not observed even in those patients with elevated FGF23, and a weak positive correlation was noted between serum FGF23 and phosphate concentrations. Malignant plasma cells in bone marrow trephines from patients with myeloma showed cytoplasmic expression of FGF23, similar to the cytoplasmic localization of FGF23 already described in mesenchymal tumors associated with oncogenic osteomalacia. Our findings contribute to an expanding literature regarding abnormal FGF/FGF receptor-signaling in myeloma. The absence of hypophosphatemia in these cases suggests either that FGF23 produced by clonal B-cells lacks systemic bioactivity or that other factors contribute to maintain serum phosphate. We suggest that the relationship between FGF23 and skeletal disease associated with plasma cell dyscrasias deserves further study.

Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome

To investigate the possible role of tryptophan metabolism in immune regulation of primary Sjögren's syndrome (pSS) the serum concentrations of tryptophan and its metabolite kynurenine were measured by reverse-phase high-performance liquid chromatography (HPLC) in 103 patients with pSS, 56 patients with sicca symptoms and 309 healthy blood donors. The kynurenine per tryptophan ratio (kyn/trp), which reflects the activity of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme involved in tryptophan catabolism, was calculated. Both female and male patients with pSS had significantly higher serum kynurenine concentrations and kyn/trp than subjects with sicca symptoms or healthy blood donors. The median (quartile range) concentration of kynurenine in female patients with pSS was 2.41 micromol/l (1.86-3.26) compared with 1.85 micromol/l (1.58-2.38, P < 0.0001) in subjects with sicca symptoms and 1.96 micromol/l (1.65-2.27, P < 0.0001) in healthy blood donors. Their kyn/trp x 1000 was 34.0 (25.1-44.3) compared with 25.3 (21.1-31.5, P < 0.0001) in subjects with sicca symptoms and 24.3 (21.0-28.9, P < 0.0001) in healthy blood donors. Female pSS patients with high IDO activity (kyn/trp x 1000 > or = 34.0) had significantly higher ESR, serum C-reactive protein, serum IgA and serum beta-2 microglobulin concentrations as well as higher serum creatinine levels, and they had positive antinuclear antibodies more frequently and presented with more American-European consensus group criteria than those with low IDO activity (kyn/trp x 1000 < 34.0). These data suggest that mechanisms dependent on tryptophan catabolism regulate immune responses in pSS. Tryptophan degradation is enhanced in patients with pSS, and high IDO activity is associated with severity of pSS.

Serum free light chains for monitoring multiple myeloma

Monoclonal immunoglobulin free light chains (FLC) are found in the serum and urine of patients with a number of B-cell proliferative disorders, including multiple myeloma. Automated immunoassays, which can measure FLC in serum, are useful for the diagnosis and monitoring of light chain (AL) amyloidosis, Bence Jones myeloma and non-secretory myeloma patients. We report the results of a study investigating the utility of serum FLC measurements in myeloma patients producing monoclonal intact immunoglobulin proteins. FLC concentrations were measured in presentation sera from 493 multiple myeloma patients with monoclonal, intact immunoglobulin proteins. Serial samples were assayed from 17 of these patients and the FLC measurements were compared with other disease markers. Serum FLC concentrations were abnormal in 96% of patients at presentation. FLC concentrations fell more rapidly in response to treatment than intact immunoglobulin G (IgG) and showed greater concordance with serum beta2 microglobulin concentrations and bone marrow plasma cell assessments. It was concluded that serum FLC assays could be used to follow the disease course in nearly all multiple myeloma patients. In addition, because of their short serum half-life, changes in serum FLC concentrations provide a rapid indication of the response to treatment.

Serum free light chains for monitoring multiple myeloma.

Monoclonal immunoglobulin free light chains (FLC) are found in the serum and urine of patients with a number of B-cell proliferative disorders, including multiple myeloma. Automated immunoassays, which can measure FLC in serum, are useful for the diagnosis and monitoring of light chain (AL) amyloidosis, Bence Jones myeloma and non-secretory myeloma patients. We report the results of a study investigating the utility of serum FLC measurements in myeloma patients producing monoclonal intact immunoglobulin proteins. FLC concentrations were measured in presentation sera from 493 multiple myeloma patients with monoclonal, intact immunoglobulin proteins. Serial samples were assayed from 17 of these patients and the FLC measurements were compared with other disease markers. Serum FLC concentrations were abnormal in 96% of patients at presentation. FLC concentrations fell more rapidly in response to treatment than intact immunoglobulin G (IgG) and showed greater concordance with serum beta2 microglobulin concentrations and bone marrow plasma cell assessments. It was concluded that serum FLC assays could be used to follow the disease course in nearly all multiple myeloma patients. In addition, because of their short serum half-life, changes in serum FLC concentrations provide a rapid indication of the response to treatment.

Bone marrow angiogenesis and its correlation with other disease characteristics in multiple myeloma in stage I versus stage II-III.

We studied bone marrow angiogenesis in different stages of multiple myeloma according to the Durie and Salmon classification and its correlations with other disease characteristics. Sixty-five immunohistochemical CD34-stained, paraffin-embedded bone marrow biopsies of multiple myeloma patients and 12 controls were studied. The mean number of microvessels per area in each sample was determined as the microvessel density (MVD). In addition, plasma cell infiltration of the bone marrow, serum beta2-microglobulin, immunoglobulin levels, C-reactive protein, and serum calcium concentration were measured in 22 patients with stage I multiple myeloma and in 43 patients in stage II-III. In myeloma patients, the bone marrow MVD was significantly higher than in controls (P<0.001). In 43 patients with stage II-III multiple myeloma, MVD was significantly higher than in 22 patients with stage I (median MVD 46 and 21 vessels/mm(2), respectively, P=0.005). Additionally, in stage II-III the bone marrow MVD correlated positively with the bone marrow plasma cell infiltration (r=0.55, P<0.001) and the serum beta2-microglobulin level (r=0.53, P<0.001), while in stage I patients no correlation could be found. Angiogenesis is significantly increased in stage II-III myeloma in comparison to stage I. In stages II-III, bone marrow angiogenesis is correlated with plasma cell infiltration and serum beta2-microglobulin levels.

Urinary β2-Microglobulin Masquerading as a Bence Jones Protein

Bence Jones proteinuria, a common clinical manifestation of multiple myeloma, can also be seen in patients with other B-cell-derived neoplasms. Measurement of pretreatment levels is a useful adjunct in the diagnosis and staging of multiple myeloma, whereas serial levels reflect response to therapy. Serum concentrations of beta2-microglobulin, a small-molecular-weight protein associated with the major histocompatibility complex class I antigens, are often elevated in hematopoietic neoplasms and are also commonly measured at baseline, before treatment, and serially throughout therapy in patients with multiple myeloma and other lymphoproliferative disorders as a marker of tumor burden. Urinary concentrations, however, are considered an indicator of renal tubular function. High urinary levels are found in tubular proteinuria, a frequent sequela of long-standing multiple myeloma. A case is described in which a high urinary concentration of beta2-microglobulin interfered with Bence Jones protein quantification by electrophoresis studies.

Serum beta2-microglobulin reflects increased bone resorption in immobilized stroke patients.

The so-called bone-derived growth factor, beta2-microglobulin, has a regulatory function in bone metabolism by stimulating osteoclast activity. We undertook this study because osteoclast activity is known to be enhanced in patients with immobilized stroke, suggesting that their beta2-microglobulin concentrations may be increased. We studied 79 patients with acute stroke hemiplegia, including 36 men and 43 postmenopausal women ranging in age between 51 and 70 yr. The mean Barthel Index was 43 and 42 for men and women, respectively. The serum beta2-microglobulin concentration was increased in male and female patients, compared with the findings of 44 age-matched control subjects, and the serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen was also increased in male and female patients, compared with the findings of the control subjects. Serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen correlated negatively with Barthel Index scores in both genders, indicating increased bone resorption caused by immobilization in these patients. Linear regression analysis revealed a positive correlation between beta2-microglobulin and pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen in both genders. These findings suggest that beta2-microglobulin reflects osteoclastic activity in response to stroke-induced immobilization in both genders. Beta2-microglobulin is a useful indicator of bone resorption in patients with immobilized stroke.

Spontaneous monoclonal immunoglobulin-secreting peripheral blood mononuclear cells as a marker of disease severity in multiple myeloma.

Peripheral blood from patients with multiple myeloma (MM) contains a small number of plasma cells related to the bone marrow tumour cells by their cytoplasmic immunoglobulin (Ig), their cell membrane antigen expression and/or their gene rearrangements, but hitherto the monoclonal Ig (M-Ig) production by circulating cells has not been reported. Using a two-colour ELISPOT assay, Ig-secreting cells (Ig-SCs) were detected in the blood of 28 MM and five Waldenstrom's macroglobulinaemia (WM) patients. The number of cells that spontaneously produced an Ig isotype similar to that of the M-Ig in serum was greater than that of the other Ig-SCs. MM patients presented an excess of circulating heavy-chain (alpha or gamma) Ig-SCs (0.38% of the PBMC) with kappa or lambda light chains (0.48%) compared with the number of cells secreting the other heavy- (0.02%) and light-chain isotypes (0.03%). WM patients also presented high numbers of cells secreting the mu-heavy-chain isotype (0.66%). The Ig synthesized in vitro was characterized as monoclonal, and the M-Ig secretory capacity of the peripheral blood cells was similar to that observed for Ig-SCs from polyclonal activated B cells in vivo. The number of these monoclonal cells was significantly increased in patients in an advanced stage of MM (I/II vs. III, P < 0.001) and correlated with the serum beta-2 microglobulin concentration (r = 0. 69; P < 0.0003). The number of M-Ig-SCs in MM patients could be a useful marker for evaluating the progression of multiple myeloma.

Flowcytomeric analysis on neutrophil intracellular enzyme activity in patients on hemodialysis and continuous ambulatory peritoneal dialysis

To elucidate the mechanism of neutrophil dysfunction in patients with maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), intracellular enzyme activity such as oxidative burst, elastase, cathepsin, and collagenase, was investigated. Response of enzyme activity to in vitro addition of TNF-alpha, which is known to have a powerful priming effect on neutrophils, was also evaluated. Peripheral blood from 15 HD and 15 CAPD patients was washed and incubated with Cell Probe, an indicator for intracellular enzyme activity. Mean fluorescent intensity of neutrophils, which represents neutrophil enzyme activity, was measured by flowcytometry. In HD group, unstimulated enzyme activity was similar to that of control, but activity after addition of TNF-alpha was significantly lower than the control. In the group of CAPD, enzyme activity without stimulation was not different from that of control, and in TNF-alpha stimulated neutrophils, only elastase activity was lower than control. Many of the enzyme activities after stimulation were lower in HD than in CAPD. Response to in vitro addition of TNF-alpha was diminished in both dialysis groups, but more prominent in HD neutrophils. Duration of dialysis, serum concentration of beta 2-microglobulin (beta 2-MG) and parathyroid hormone (PTH) was significantly related inversely to intracellular enzyme activity in HD patients. To the contrary, in CAPD group, although beta 2-MG and PTH showed similar negative correlation, duration of dialysis was not related to enzyme activity. These results indicate that neutrophils in patients with maintenance dialysis have diminished intracellular oxidative burst, elastase, and cathepsin activity. Especially, impaired response to TNF-alpha closely related to neutrophil dysfunction in dialysis patients.

Beta 2-microglobulin does not behave as a biological marker of bone remodelling in patients with primary hyperparathyroidism

Parathormone has been shown to increase the secretion and production of lysosomal enzymes including tartrate-resistant acid phosphatase. All our 68 patients with proven primary hyperparathyroidism had signs of hyperparathyroid bone disease. Tartrate-resistant acid phosphatase and bone alkaline phosphatase activities are raised as a result of enhanced bone remodelling. Serum beta 2-microglobulin concentration in patients with primary hyperparathyroidism was normal 1.6 (1.4–1.8) mg/l versus 1.8 (1.7–2.2) mg/l in 51 control subjects. In hyperparathyroid patients, serum beta 2-microglobulin concentration does not correlate with plasma tartrate-resistant acid phosphatase activity which is known to be a sensitive biological marker of bone remodelling (r=0.088). Our findings indicate that serum beta 2-microglobulin does not behave as a biological marker of remodelling in patients with enhanced remodelling in primary hyperparathyroidism.

Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta-1a after intramuscular and subcutaneous administration.

The pharmacokinetics and pharmacodynamics of recombinant human interferon beta (IFN-beta-1a) were compared after intramuscular administration of two preparations (Rebif(R) and AvonexTM) and subcutaneous administration of Rebif(R). Healthy volunteers (n = 30) received a single dose (60 µg) of each of the three treatments in a randomised crossover study. Serum concentrations of IFN-beta were measured by enzyme-linked immunosorbent assay over 24 h after dosing. Pharmacodynamics were assessed by measurement of intracellular 2',5'-oligoadenylate synthetase activity, and serum neopterin and beta2-microglobulin concentrations, over 144 h after dosing. There was no significant difference between the three treatments in peak serum IFN-beta concentrations (Cmax) or area under the concentration-time curve (AUC). No significant differences in pharmacodynamic measures were observed between the three treatments. It is concluded that the bioavailability of IFN-beta-1a is equivalent after subcutaneous or intramuscular administration of Rebif(R), and intramuscular administration of AvonexTM. Copyright Rapid Science Ltd

Predictors of progression in long-term nonprogressors. Australian Long-Term Nonprogressor Study Group.

It is now apparent that a proportion of individuals (5-8%) remains clinically free of HIV-1 disease with normal levels of CD4+ lymphocytes (> or =500/microl) for more than 8 years following infection. However, the proportion of these individuals who ultimately progress to AIDS remains to be established. We determined the virological and immunological characteristics of a cohort of long-term nonprogressors in Australia and examined the role of these factors in predicting disease progression. Individuals with documented asymptomatic HIV-1 infection for at least 8 years with CD4+ lymphocyte counts >500 cells/microl were recruited from hospital clinics and general practices serving the eastern area of Australia. CD4+ lymphocyte count, rate of CD4+ lymphocyte change, CD8+ lymphocyte count, beta2-microglobulin, immune complex dissociated (ICD) HIV-1 p24 antigen, and plasma HIV-1 RNA were measured at baseline and multiple visits at 6-month intervals over an average period of 2 years. Up to November 1996, 67 study participants were recruited, of whom 72% had been infected with HIV-1 for at least 10 years. HIV-1 RNA correlated with beta2-microglobulin, ICD p24 antigen, and the ability to isolate virus in culture but not with levels of CD4+ or CD8+ lymphocytes. Serum beta2-microglobulin was a stronger predictor of CD4+ lymphocyte decline than HIV-1 RNA and the only factor significantly associated with CD4+ lymphocyte decline. These findings show that the serum concentration of beta2-microglobulin is a strong predictor of immunological progression in people with long-term asymptomatic HIV-1 infection and provides additional prognostic information to HIV-1 RNA in determining the risk of disease progression.

Effects of alpha-interferon on serum beta-2-microglobulin.

Beta-2-microglobulin (B2M) forms the small invariable light chain subunit of class I HLA antigens on the cell membrane of all nucleated cells. During the continuous turnover of the HLA molecules, B2M is shed from the cell membrane into blood. Lymphocytes are the main source of serum free B2M. Serum B2M concentration is increased in renal diseases, various malignant diseases and some inflammatory and autoimmune disorders. In lymphatic malignancies serum B2M has significant prognostic value. Interferons (IFNs) have the ability to enhance the expression of class I and II histocompatibility antigens. Accordingly, IFNs cause a rise in formation and release of B2M. Currently, treatment with IFN alpha is used in diseases, like multiple myeloma, where serum B2M measurements are used to assess tumor burden. We have measured serum B2M levels during IFN alpha treatment in patients with both multiple myeloma and chronic myeloproliferative diseases, and IFN alpha caused a significant increase in serum B2M. It can be concluded that use of IFN alpha abolishes the value of serum B2M as an indicator of disease activity.

Serum beta 2-microglobulin in chronic diseases of the pancreas.

Elevated serum concentrations of beta 2-Microglobulin (beta 2-MG) has been reported in a variety of chronic diseases and solid tumors. We determined serum beta 2-MG concentrations in 140 subjects divided into five groups: group 1, 34 patients with proven chronic pancreatitis, 8 of whom were studied during a painful relapse; group 2, 40 patients with pancreatic cancer staged according to the Cubilla-Fitzgerald classification; group 3, 40 healthy subjects; group 4, 10 patients with digestive nonpancreatic carcinomas; group 5, 16 patients with benign digestive nonpancreatic diseases. Serum soluble interleukin-2 receptor (sIL-2R) was also determined in all patients with pancreatic diseases as an index of immune system activation. In addition, serum CA 19-9 was assayed in patients of groups 2 and 4, and C-reactive protein (CRP) of groups 1 and 5. Renal function, evaluated by serum creatinine determination, was normal in all subjects studied. Patients with pancreatic cancer and those with chronic pancreatitis had serum concentrations of beta 2-MG significantly higher than those of healthy subjects (p < 0.001 and p < 0.005, respectively). Patients with stage I and stage III pancreatic cancer had similar serum levels of beta 2-MG, and these concentrations were significantly lower than those of patients with stage II tumors (p < 0.002 and p < 0.05, respectively). In chronic pancreatitis patients, those studied during painful relapse of the disease had serum concentrations of beta 2-MG similar to those studied during clinical remission.(ABSTRACT TRUNCATED AT 250 WORDS)