Beta 2-microglobulin Concentrations Research Articles

High phosphorus diet rapidly induces nephrocalcinosis and proximal tubular injury in rats.

The development of nephrocalcinosis and the time course of changes in kidney function, especially proximal tubular function, were studied in young male rats fed a high-phosphorus diet. The animals were fed a purified diet with a phosphorus content of either 0.5% (normal phosphorus diet) or 1.5% (high-phosphorus diet). In the group fed the high-phosphorus diet, nephrocalcinosis was found in 4 of 42 rats after 1 d of feeding and in all rats of this group at 3 d. The degree of nephrocalcinosis gradually increased with time. Upon histological observation by electron microscopy, vacuoles, lysosomes and swelling of microvilli in the proximal tubules were observed in rats fed the high-phosphorus diet after 1 d of feeding. Giant lysosomes with deposition of calcium and deposition of hydroxyapatite in mitochondria were observed in the proximal tubules of rats fed the high-phosphorus diet at 3 d. Albumin concentration in the urine of these rats was significantly increased at 3 d. The activity of N-acetyl-beta-D-glucosaminidase in the urine was also significantly increased after 1 d of feeding the high-phosphorus diet, and then reached a plateau. The beta 2-microglobulin concentration in the urine of rats fed the high-phosphorus diet was significantly increased at 14 d, and increased more toward 21 d. We concluded that nephrocalcinosis and injury to the proximal tubules are rapidly induced in rats fed a high-phosphorus diet.

Serum Levels of Soluble IL-6 Receptor in Multiple Myeloma as Indicator of Disease Activity

Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 50 patients with plasma cell dyscrasias using a commercially available immunoenzymatic assay kit. There were 40 patients with multiple myeloma (MM), 5 patients with monoclonal gammopathy of undetermined significance (MGUS), 3 patients with solitary plasmacytoma (SPC), 1 patient with chronic myelogenous leukaemia and multiple myeloma (CML/MM), and 1 patient with plasma cell leukaemia (PCL). We found that serum sIL-6R concentrations were higher in MM patients (62.53 +/- 38.85 ng/ml) than in 20 normal volunteers studied (36.75 +/- 13.79 ng/ml) (p < 0.01). The cut-off value of 65 ng/ml seen in 2 of our controls was arbitrarily taken as the upper limit of the control range for serum sIL-6R; according to this criterion, 14 patients with MM (35%), 1 patient with SPC, the unique patient with CML + MM, and the unique patient with PCL had elevated concentrations of the receptor. Patients with MGUS had normal sIL-6R values. In MM patients, serum sIL-6R levels correlated with the clinical phase of the disease: they were elevated in patients with early or late active disease and ranged within normal limits in patients with plateau-phase disease (p < 0.001). Thirteen of 27 patients with active MM had elevated serum sIL-6R values, i.e. 48.1%, but only 1 out of 13 patients with disease in the plateau phase, i.e. 7.7% (p < 0.05). Furthermore, in the entire group of MM patients, serum sIL-6R levels correlated with the concentrations of serum beta 2-microglobulin, (p < 0.02), CRP (p < 0.01), ferritin (p < 0.01) and LDH (p < 0.01), while they did not correlate with disease stage, haemoglobin levels, proportion of marrow myeloma cells, the values of serum IL-6, the levels of serum albumin, or the grade of bone lesions. We conclude that elevated serum sIL-6R levels should be related to the growth of myeloma cells and suggest that serum sIL-6R concentrations may be used as an indicator of disease activity.

Immunoglobulin and beta 2-microglobulin concentrations in bronchoalveolar lavage of children and adults.

Immunoglobulins play an important role in the pulmonary host defense, but little information is available about immunoglobulin and beta 2-microglobulin concentrations in the lung of normal children. Using bronchoalveolar lavage (BAL) we have studied immunoglobulin and beta 2-microglobulin levels in 30 children 3-15 years old undergoing elective surgery for nonpulmonary illnesses and in 15 healthy adult volunteers. BAL was performed with 3 x 1 ml/kg of body weight normal saline through an endotracheal tube after induction of anesthesia in children and under local anesthesia in adults. Similar concentrations of IgA and IgG were found in BAL fluid of children and adults even though serum levels were lower in children. As comparable results were obtained for albumin, a serum-derived protein, these data suggest that the permeability of the alveolar membrane is higher in children. IgE and IgM were detected in BAL fluid in only a fraction of children. beta 2-microglobulin levels were higher in both blood and BAL fluid of children. These data provide the first reference data for immunoglobulin and beta 2-microglobulin in children and can serve as a basis for future studies of children with pulmonary diseases.

Development of human renal function: reference intervals for 10 biochemical markers in fetal urine

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (< or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Characterization of Myeloma Cells by Means of Labeling Index, Bone Marrow Histology, and Serumβ2-Microglobulin

The relationship between two cellular prognostic parameters of multiple myeloma, the plasma cell labeling index (LI%) and bone marrow histology was studied. The LI% as the percentage of monoclonal plasma cells in the S-phase was measured by bromodeoxyuridine incorporation using the anti-bromodeoxyuridine antibody BU-1. The histologic classification was based on six plasma cell types that allow prognostic grading as the Marschalko, small cell, cleaved, polymorphous, asynchronous, and blastic types. The biopsies also were used for estimating the degree of infiltration. Beta 2-microglobulin (IMx assay, Abbott, North Chicago, IL), the most significant serum parameter for myeloma also was measured for comparison. Bone marrow specimens and sera were obtained from 50 myeloma patients. Fourteen patients with smoldering myeloma were characterized by well-differentiated Marschalko or small cell type cells, a low LI% and a low beta 2-microglobulin concentration. Considering all myeloma patients, plasma cell type and degree of infiltration showed a significant correlation with LI% and beta 2-microglobulin concentration. Patients with plasma cells that were not mature cells of the Marschalko or small cell type revealed a high LI% or high beta 2-microglobulin level in 16 of 19 cases. However, a high LI% or high beta 2-microglobulin level could be detected in only 8 of 31 patients with plasma cells of the Marschalko or small cell type. Three of 21 stage I patients did not show the typical finding of a low LI%, low beta 2-microglobulin level, and a favorable grade. Stage II patients were not uniformly characterized by LI%, beta 2-microglobulin and plasma cell morphology. The percentage of nucleolated plasma cells was not associated with the LI%. Bone marrow histology, LI%, and beta 2-microglobulin concentration appear to be supplementary prognostic factors. If LI% and beta 2-microglobulin levels are not measured, a higher risk could be overlooked in cases with mature plasma cells.

Rapid Decline of Residual Renal Function in Patients on Automated Peritoneal Dialysis

To determine the effect of peritoneal dialysis modalities such as nightly intermittent peritoneal dialysis (NIPD), continuous cyclic peritoneal dialysis (CCPD), and continuous ambulatory peritoneal dialysis (CAPD) on residual renal function. A six-month prospective, nonrandomized comparison study. Outpatient CAPD unit of a university hospital. Eighteen end-stage renal disease patients treated by peritoneal dialysis (8 by NIPD, 5 by CCPD, and 5 by CAPD). Samples from the total dialysate, blood, and 24-hour urine collection were obtained monthly. Urea, creatinine, and beta2-microglobulin concentrations were measured. Renal and peritoneal clearances of each substance and KT/V urea were calculated. Residual renal function (RRF) was estimated by renal creatinine clearance (RCcr). No significant differences in age, sex, and primary renal disease among the three groups were noted. In all groups, anemic and hypertensive states were controlled identically, and mean weekly total (renal + peritoneal) KT/V urea (over 2.1/wk) and total creatinine clearance (over 60 L/wk/1.73 m2) were maintained during the whole experimental period. Starting mean RCcr was near 4.0 mL/min/1.73 m2 in all groups. Thereafter, a rapid and significant decline in RRF was demonstrated on NIPD and CCPD. The declining rates of RCcr values at 6 months after starting NIPD and CCPD were -0.29 and -0.34 mL/min/month, respectively, which were much greater than those of CAPD (+0.01 mL/min/month). Because of a possibly characteristic progressive loss of RRF in automated peritoneal dialysis (APD), strict regular assessment of RRF should be performed from the start of APD.

A New Polymethylmethacrylate Membrane for Hemodialysis

High molecular weight (MW) solutes are not removed during conventional hemodialysis (HD), and their accumulation is thought to play a role in some long-term HD complications (anemia, bone and joint pain, neuropathy, itching). The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate (PMMA) membrane (Filtryzer BK-F, 1.3 m2) compared to conventional PMMA (BK-P, 1.6 m2) and to cellulose acetate (CA, 1.3 m2). BK-F dialyzers, with a pore size of 100 A degrees and 62% porosity, are designed to remove high MW substances. Ten stable anuric RDT patients (53 +/- 13 years) were treated for one week with each membrane in a randomized sequence. Plasma concentrations of creatinine, BUN and beta 2-microglobulin (beta 2-M) were measured before (b) and after (a) HD to determine the reduction rate for these substances (%). Beta 2-M concentration after HD was corrected for changes in distribution volume. Samples of spent dialysate were collected after 3 minutes, 120 minutes and at the end of HD sessions, and appropriately treated and concentrated for HPLC analysis. The reduction rate for BUN and creatinine was similar for the 3 membranes. BK-F showed a higher beta 2-M reduction rate than BK-P (p < 0.005) or CA (p < 0.0001). HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons (kDa) throughout HD for BK-P and CA. Solutes > 10 kDa were infrequently detected. Peak profile during HD with BK-F was quite different, showing a predominant peak > 50 kDa which also included albumin. However, albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values, and was lower than that reported in CAPD patients. With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors. Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances, thereby preventing or controlling some long-term HD complications such as anemia or beta 2-M amyloid formation.

Similar Pleural Fluid Findings in Pleuropulmonary Tularemia and Tuberculous Pleurisy

Biochemical and cellular characteristics of pleural fluid from two patients with pleuropulmonary tularemia and 39 patients with tuberculous pleurisy were compared. High pleural fluid concentrations of adenosine deaminase, lysozyme, and beta 2-microglobulin occurred in both diseases. As is the case with tuberculous pleural effusions, pleural fluid in tularemia showed an abundance of lymphocytes, predominantly CD4-positive T lymphocytes. The similar pleural fluid findings suggest analogous local pathogenetic mechanisms in tularemia and tuberculosis. In the diagnostic evaluation of a lymphocyte-rich exudative pleural effusion with a high adenosine deaminase concentration, a possible cause to consider is tularemia.

Plasma allantoin in patients undergoing maintenance hemodialysis

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p < 0.0005, r = 0.313, p < 0.005, r = 0.368, p < 0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

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)

The diagnosis value of β2-microglobulin and immunoglobulins in primary Sjögren's syndrome

Salivary and serum concentrations of beta 2-microglobulin, salivary levels of the immunoglobulins, and salivary flow (as measured by a gravimetric method) were assessed in 34 patients and 11 controls. Of the 34 study patients, 16 had a primary form of Sjögren's syndrome (pSS) and 18 had sicca syndrome. The salivary and serum concentrations of beta 2-microglobulin and salivary levels of IgA and IgG were much higher in the patients with pSS than in controls or those with sicca syndrome (p < 0.001). Similarly, the salivary IgM levels of patients with pSS were higher (although at a lower degree of statistical significance) as compared to those of patients with sicca syndrome (p < 0.01) or controls (p < 0.05). No correlation was observed among the salivary flow and the salivary IgG and IgM levels, while there was a negative relationship (p < 0.01 with salivary IgA levels in all 45 patients considered as a whole. In 12 patients with pSS, the coefficient of correlation between the salivary gland biopsy focus score and the salivary (but not serum) concentration of beta 2-microglobulin was highly significant (p < 0.001). A similar relationship was observed with the IgG (p < 0.001) and IgM (p < 0.05) levels, but not IgA. In the diagnosis of pSS, the salivary IgA level demonstrates high sensitivity and low specificity. In contrast, serum and salivary concentrations of beta 2-microglobulin, salivary IgG, and to a lesser degree, salivary IgM have high specificity and positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum beta 2-microglobulin and prediction of progression to AIDS in HIV-infected injection drug users.

Several immunological and serological variables have become established in recent studies as valuable markers to identify human immunodeficiency virus (HIV)-positive individuals at the highest risk for rapid disease progression. These studies have been performed mainly in cohorts of homosexual men. In this study, we assessed the usefulness of CD4 lymphocyte count, serum beta 2-microglobulin concentration, and the presence of p24 antigen as predictors of AIDS in a cohort of 130 HIV-positive injection drug users (IDUs) followed-up for 1 to 67 months. Progression to AIDS was most strongly associated with reduced absolute numbers of CD4+ lymphocytes at baseline, but increases in beta 2-microglobulin levels at baseline were an independent predictor of outcome. After stratification by baseline CD4 count, beta 2-microglobulin concentration added significant prognostic information to CD4 count among IDUs with > 500/mm3 CD4 cells (Breslow statistic value, 5.84, p = 0.01). Thus among seropositive IDUs with normal CD4 counts, increases in beta 2-microglobulin may be used as an early marker of individuals with higher risk of progression to AIDS, who may benefit from more intensive laboratory monitoring or clinical management.

Age, gender, and other predictors of the wasting syndrome among HIV-1-infected injecting drug users.

We conducted a study to identify predictors of the wasting syndrome among human immunodeficiency virus 1 (HIV-1)-seropositive injecting drug users. We enrolled 113 cases (defined as an unexplained loss of > 10% baseline weight) and 226 controls (defined as < 5% weight loss or any weight gain) from a HIV-1-seropositive cohort of injecting drug users (N = 630) into a nested case-control study. Crude predictors of wasting included: older age [odds ratio (OR) for a 1-year difference = 1.06], female gender (OR = 1.66), more years spent injecting drugs (OR for 1-year difference = 1.05), presence of diarrhea (OR = 3.78), lower percentage of CD4 T-lymphocytes (OR for 10-unit difference = 0.73), and higher log beta 2-microglobulin concentration (OR for 1 log difference = 11.3). After adjusting for CD4 cell level, beta 2-microglobulin concentration, diarrhea, gender, length and frequency of drug use, age, the presence of thrush, and education, independent predictors of weight loss in HIV-seropositive injecting drug users were female gender (OR = 2.23) and increasing age (OR for 1-year difference = 1.06). Frequency and duration of drug use were not strongly associated with the odds of developing wasting syndrome in this HIV-1-seropositive cohort. These data indicate that HIV wasting syndrome in injecting drug users is distinct from complications of drug use.

Brain beta 2-microglobulin levels are elevated in the striatum in Parkinson's disease.

beta 2-Microglobulin (B2-MG) content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) from control and parkinsonian patients by a highly sensitive sandwich enzyme immunoassay. The concentrations of B2-MG in dopaminergic striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex showed no significant difference between parkinsonian and control subjects. Tumor necrosis factor-alpha (TNF-alpha) concentrations were also increased in the striatum, confirming our previous findings, but not in the cerebral cortex. Since TNF-alpha may induce B2-MG expression, these results suggest that an immunological response may occur in the nigrostriatal dopaminergic regions in Parkinson's disease.

Effect of Iopentol on Renal Function and Its Use for Calculation of Glomerular Filtration Rate in Children

Nineteen children received 99mTc-DTPA for renography. The next day they received a simultaneous injection of the non-ionic contrast medium iopentol for urography and another injection of 99mTc-DTPA. The glomerular filtration rate (GFR) was estimated from the plasma elimination of 99mTc-DTPA as well as iopentol. Serum concentrations of creatinine and beta 2-microglobulin, and urine concentrations of creatinine, beta 2-microglobulin, alkaline phosphatase, N-acetyl-glucosaminidase, and albumin were determined. A significant reduction (12 +/- 3%) of GFR was observed after the injection of iopentol, without a subsequent rise in serum creatinine or beta 2-microglobulin. The urinary excretion of albumin and beta 2-microglobulin remained unchanged, while the excretion of alkaline phosphatase and N-acetyl-glucosaminidase was significantly increased after the urography, indicating some tubular effects of iopentol. Iopentol caused few and mild adverse events, the diagnostic yield was high, and the small changes in the renal tubular function parameters are presumed to be without clinical importance. The observed depressive effect on the GFR demands further investigations before iopentol can be recommended as a GFR-marker in children.

HIV type 1-specific cytotoxic T lymphocytes stimulate HLA class I and intercellular adhesion molecule type 1 expression and increase beta 2-microglobulin levels in vitro.

Besides acting in a direct manner, cytolytic HIV-1-specific CTLs release a variety of cytokines. To assess the potential role of cytokines released by these CTLs we tested the ability of soluble products secreted by HIV-1-specific CTLs to induce HLA class I and ICAM-1 expression and to raise beta 2-microglobulin (beta 2M) concentrations in cell culture. To this end, supernatants were derived from HIV-1-specific CTLs incubated with autologous B lymphoblasts presenting either the cognate HIV-1 epitope or a control peptide. Cell lines and peripheral blood mononuclear cells (PBMCs) were incubated with these supernatants for 24-48 hr. Similarly, cells were cocultured with CTLs and their targets. This study demonstrates that in parallel with lysis of their cognate target, HIV-1-specific CTLs secreted products that stimulated HLA class I and ICAM-1 expression on cell lines and PBMCs. As few as 1000 CTLs significantly induced the expression of these molecules. In addition, secreted products of HIV-specific CTLs enhanced beta 2M release by PBMCs and Jurkat cells. These effects were mediated primarily by IFN-gamma and suggest that HIV-specific CTLs may contribute to increased HLA class I expression in infected tissue and elevated ICAM-1 and beta 2M concentrations in serum and cerebrospinal fluid of infected individuals.

Spontaneous In Vitro Anti-Human Immunodeficiency Virus Type 1 Antibody Secretion By Peripheral Blood Mononuclear Cells Is Related To Disease Progression In Zidovudine-Treated Adults

As part of a continuous search for surrogate markers of therapeutic efficacy in AIDS, spontaneous in vitro production by peripheral blood mononuclear cells of antibody to human immunodeficiency virus type 1 (HIV-1) was investigated in 50 HIV-1-infected adults. It was independent of CD4+ cell counts, p24 antigenemia, serum beta 2-microglobulin concentration, and clinical status of the patients. The effect of zidovudine on this antibody secretion and the appearance of signs or symptoms of HIV-1 disease progression were evaluated in 20 patients over 24 weeks. Anti-HIV-1 antibody secretion decreased significantly (P = .002) as of the first month of zidovudine treatment only in the 13 HIV-1-infected patients without disease progression. This is earlier than the occurrence of variations in CD4+ cell count and serum beta 2-microglobulin concentration. These results suggest that in vitro antibody production could be a surrogate marker for evaluation of the in vivo antiretroviral efficacy of zidovudine, even in p24 antigen-negative patients.

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L-1 of urine (range: 0.17-546.31 pmol/L-1. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary beta 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.

Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha.

To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.