Serum Levels Of Carbohydrate-deficient Transferrin Research Articles

Determination of serum carbohydrate-deficient transferrin by a nephelometric immunoassay for differential diagnosis of alcoholic and non-alcoholic liver diseases

BackgroundCarbohydrate-deficient transferrin is a biological marker of excessive drinking. The aim of this study was to evaluate the diagnostic value of a direct nephelometric immunoassay for the differential diagnosis of alcoholic and non-alcoholic liver diseases in comparison with gamma glutamyl transferase. MethodsSerum samples were obtained from 305 subjects, including 122 patients with alcoholic and 102 cases with non-alcoholic liver diseases. Serum levels of carbohydrate-deficient transferrin were expressed as a percentage of total transferrin. ResultsSerum % carbohydrate-deficient transferrin levels were significantly higher in patients with alcoholic than with non-alcoholic liver diseases. Carbohydrate-deficient transferrin had better specificity than gamma glutamyl transferase to differentiate between alcoholic and non-alcoholic liver diseases.There were 8 alcoholic liver disease patients with normal gamma glutamyl transferase levels, and carbohydrate-deficient transferrin was significantly elevated in 6 of them. On the other hand, there were 25 non-alcoholic liver disease patients with elevated gamma glutamyl transferase levels; their carbohydrate-deficient transferrin levels were within the reference intervals in all cases. ConclusionThis simple carbohydrate-deficient transferrin immunoassay is useful to detect so-called gamma glutamyl transferase non-responding drinkers and also to exclude the possible role of excessive drinking in apparently non-alcoholic liver diseases. A large-scale prospective study is needed to further confirm the diagnostic utility of carbohydrate-deficient transferrin.

RAPID ALTERATIONS IN TRANSFERRIN SIALYLATION DURING SEPSIS

The inflammatory process is associated with alterations in iron metabolism. Transferrin, an acute-phase N-glycosylated glycoprotein, plays an important role in iron transport. Human serum transferrin contains two biantennary glycans, each consisting of 0 to 4 molecules of sialic acid (SA); its SA content is heterogeneous with high concentration of tetrasialotransferrin (4SA) and low amounts of disialo-, trisialo-, penta-, and hexasialotransferrin. The hepatic uptake of iron is greater for desialylated transferrin isoforms (disialotransferrin) than for the other forms. We hypothesized that serum levels of carbohydrate-deficient transferrin (CDT, disialotransferrin) may increase rapidly in septic patients. Blood samples were obtained from critically ill patients with (n = 15) and without (n = 14) documented sepsis and compared with healthy volunteers. The different forms of transferrin were studied by capillary zone electrophoresis; SA concentrations were measured by enzymatic colorimetric assay. There was a significant increase in the proportion of CDT in septic compared with nonseptic patients and volunteers (18.3% [1.3-30.5] vs. 0.7% [0.5-0.9]; P < 0.01 and 0.9% [0.5-1.1]; P < 0.05). Conversely, tri- and tetrasialotransferrin levels were lower in septic patients. Total and free SA concentrations were significantly higher in septic patients than in healthy volunteers. In a sheep model of septic shock secondary to peritonitis, serum free SA was already increased after 15 h. Sepsis is associated with decreased SA content on circulating transferrin and with an increase in blood free SA concentrations. In view of these rapid modifications and the long half-life of transferrin, the most likely explanation is degradation of transferrin by neuraminidase. Further studies including measurement of blood neuraminidase concentration and activity are needed to understand the process and exact role of SA decrease in septic patients.

Cardiac Manifestations of Carbohydrate-Deficient Glycoprotein Syndrome

A 2-month-old girl with exudative pericarditis and hypertrophic obstructive cardiomyopathy is presented. The child had characteristic dysmorphic features of carbohydrate-deficient glycoprotein syndrome, which was confirmed by serum levels of carbohydrate-deficient transferrin.

Increased serum levels of carbohydrate-deficient transferrin in patients with chronic obstructive pulmonary disease.

The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = -0.81, p = 0.001). These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.

Usefulness of carbohydrate-deficient transferrin and trypsin activity in the diagnosis of acute alcoholic pancreatitis

OBJECTIVE: The aim of this study was to assess if carbohydrate-deficient transferrin (CDT) and trypsin activity differentiate acute alcoholic pancreatitis from nonalcohol-related pancreatitis, and as a secondary goal to evaluate its use in comparison to healthy controls. METHODS: Serum levels of CDT and trypsin activity were measured in frozen sera from 70 nonconsecutive patients with acute pancreatitis and in 16 healthy controls. RESULTS: Causes of pancreatitis were gallstones in 51%, chronic alcoholism in 23%, and other or unknown causes in 26% of the patients. Serum CDT was significantly higher in alcoholic pancreatitis than in the nonalcoholic disease ( p < 0.0001) with a median (interquartile range) of 30.8 U/L (23.6–41.7 U/L) in chronic alcoholism, 16.7 U/L (13.05–21.1 U/L) in gallstones, 17.5 U/L (15.9–21.6 U/L) in unknown cause, 19.3 U/L (15.1–27.7 U/L) in other etiologies, and 16.1 U/L (12.1–18.8 U/L) in controls. At a cutoff over 22.5 U/L, CDT showed a sensitivity of 87.5% and a specificity of 85.2%. Serum levels of trypsin activity were significantly higher ( p = 0.0007) in alcoholic pancreatitis, median 165 U/L (76–405 U/L) than in nonalcoholic pancreatitis, median 73 U/L (46.5–100.5 U/L). At a cutoff value over 152 U/L, the sensitivity of trypsin activity was 60% with a specificity of 100%. In the multivariate analysis, patient’s age (≤44 yr), CDT (>22.5 U/L), and trypsin activity (>152 U/L) enabled correct prediction of acute alcoholic pancreatitis in 98% of the cases. CONCLUSION: Serum CDT and trypsin activity are of clinical utility in differentiating alcoholic from nonalcoholic acute pancreatitis.

Increased serum levels of carbohydrate-deficient transferrin in patients with chronic obstructive pulmonary disease

Objective: The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. Method and results: A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r =- 0.81, p = 0.001). Conclusion: These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.

Utility of Biological Markers during Outpatient Treatment of Alcohol‐Dependent Subjects: Carbohydrate‐Deficient Transferrin Responds to Moderate Changes in Alcohol Consumption

A group of 25 alcohol-dependent subjects in outpatient treatment were monitored for a period of 4 weeks. They were weekly interviewed for their alcohol consumption and their serum levels of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were analyzed. The majority of the patients reported an excessive and fairly constant alcohol intake during the observation period. When selecting those patients that reported periods of 1 or 2 weeks with moderate changes in alcohol consumption, corresponding changes in CDT were demonstrated. Thus, of 14 patients reporting an increased alcohol consumption for 2 weeks (mean values increased from 57 to 101 g/day), 11 showed an increase in CDT at the end of the period. The mean CDT value of all 14 increased from 5.5 to 6.7% (p < 0.05). Slight, but not significant, increases were noted in GT, indicating that CDT is more sensitive than GT in detecting increased alcohol consumption. Furthermore, of 17 patients that reported decreased alcohol consumption for one or several weeks, 14 showed decreased CDT and GT values. The mean values of all 17 were reduced from 5.1% to 4.5% (CDT) and from 126 units/liter to 97 units/liter (GT) (p < 0.05 for both parameters). The results indicate that CDT responds to moderate changes in alcohol consumption in alcohol-dependent patients and may thus be useful as a corrective tool to self-reports of alcohol consumption during outpatient treatments.

Carbohydrate‐Deficient Transferrin Levels in a Female Population

Female college students (n = 49) from a small southwestern United States university participated in the 9-month study. Data collected included the assessment of drinking habits and other related substance use habits and serum levels of carbohydrate-deficient transferrin (CDT). Each subject provided an interview and blood sample on three occasions at 90-day intervals. Appended to the interview were a series of questions regarding stage of menstrual cycle and the diagnoses of certain diseases. The CDT values obtained were consistent with those obtained in other studies. Moderate-drinking subjects had significantly higher CDT values than did the abstainers and light drinkers. Females using oral contraceptives had significantly higher CDT values than those who were not taking oral contraceptives. Finally, although CDT values varied over time, they did not appear to vary as a function of menstrual cycle stage.

CORRELATIONS BETWEEN ACETALDEHYDE-MODIFIED HAEMOGLOBIN, CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) AND HAEMATOLOGICAL ABNORMALITIES IN CHRONIC ALCOHOLISM

Serum levels of carbohydrate-deficient transferrin (CDT), the proportions of eight haemoglobin fractions separated by cation exchange liquid chromatography, indices of liver function and various haematological parameters were determined in most of a group of 49 chronic alcoholics who had misused alcohol for at least the preceding 3 months and in 15 healthy non-alcoholic control subjects. The percentages of alcoholics giving abnormally high values for gamma-glutamyl transferase (GGT) activity, CDT levels, GGT activity or CDT levels or both, and aspartate aminotransferase (AST) activity were, respectively, 73.0, 71.0, 87.1 and 64.4. The percentages of patients giving abnormally high values for the proportion of HbA1a, proportion of HbA1ach, proportion of HbA1a or HbA1ach or both, MCH, MCV and red cell distribution width (RDW) were, respectively, 46.8, 25.5, 55.3, 55.3, 36.2 and 29.8. Reduced values for the red cell folate concentration, lymphocyte count and platelet count were found in 36.2%, 6.4% and 17.0%, respectively, of the alcoholics. When compared with the control subjects, the group of alcoholics showed statistically significant increases in the mean values for the MCV, MCH, MCHC and RDW and statistically significant decreases in the mean values for the haemoglobin distribution width (HDW) and the logarithms of the holo-transcobalamin II concentrations and the platelet count. The logarithms of the CDT values correlated directly with the MCV and MCH and inversely with the logarithms of the lymphocyte or platelet counts and the HDW, suggesting but not proving that the haematological changes in chronic alcoholism may be at least partly related to defective glycosylation of the constituents of developing blood cells or, possibly, of haemopoietic growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum Level of Carbohydrate-Deficient Transferrin as a Marker of Alcoholic Liver Disease

Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease.

Iron uptake from transferrin and asialotransferrin by hepatocytes from chronically alcohol-fed rats.

Chronic alcohol intake is often associated with alterations to iron homeostasis and an increase in the serum levels of carbohydrate-deficient transferrin. As the liver is a major iron storage site and also synthesizes transferrin, the normal serum iron transport protein, the aim of this study was to test the hypothesis that these disturbances in iron homeostasis were caused by altered hepatocyte iron uptake from the abnormal transferrin. To achieve this, we have investigated iron uptake from both transferrin and asialotransferrin by hepatocytes from male Sprague-Dawley rats fed the De Carli and Lieber alcohol diet. Iron uptake from transferrin by hepatocytes from alcoholic rats was less than 60% that of control values, and in the presence of 50 mM ethanol decreased still further to 35% of the uptake by the corresponding control cells. Iron uptake from rat asialotransferrin was reduced in both groups when compared to that observed from normal transferrin; 13% by control cells and 39% by hepatocytes from alcohol-fed rats. Alcohol, however, had no further effect on asialotransferrin uptake by either hepatocytes from alcohol-fed rats, or their pair-fed controls. Transferrin binding to hepatocytes was also influenced by the alcohol diet. Although there was no difference in binding at 37 degrees C, cells from alcohol-fed rats bound 85% of this total at 4 degrees C, compared to 44% by control hepatocytes. Similar values were also obtained for hepatocyte binding of asialotransferrin; alcohol feeding resulted in an increase in binding at 4 degrees C to 73% from 58% with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in carbohydrate-deficient transferrin levels after alcohol withdrawal.

Sequential serum levels of carbohydrate-deficient transferrin (CDT) were determined in 72 alcoholics at various intervals during detoxification. Before treatment, 57 patients (79%) had increased CDT values (Group A), whereas in 15 individuals (21%) (Group B), CDT levels were within the normal range. In 51 Group A patients, CDT decreased progressively after cessation of alcohol intake (half-life, 16 +/- 5 days), but fluctuated and remained abnormal in the remaining six. Nine Group B patients maintained normal CDT values throughout the follow-up period, but slightly or moderately increased levels were recorded on one occasion in the other six Group B subjects. Patients whose CDT levels had reached normal values after treatment, showed a recurrent increase in CDT after a relapse. gamma-Glutamyl transferase activities, which were elevated in 56% of Group A and in 80% of Group B alcoholics, showed a decrease after cessation of alcohol consumption in most patients with initially elevated values (Group A, 30 of 32; Group B, 10 of 12). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as mean corpuscular volumes (MCV) were normal in the majority of patients. CDT/total transferrin ratios correlated positively with CDT levels. CDT proved to be the most sensitive marker for chronic alcoholism (79%), whereas GGT activity levels were more useful only in patients with normal CDT levels before alcohol withdrawal. In the assessment of treatment outcome, the combination of CDT and GGT as markers yielded a sensitivity of 95%.

Carbohydrate-deficient transferrin, a marker for chronic alcohol consumption in different ethnic populations.

Serum levels of carbohydrate-deficient transferrin (CDT) were determined in a racially mixed population of 107 alcoholics, 18 healthy, nonalcoholic control subjects, 62 abstinent alcoholics, and in 64 Caucasian patients with various nonalcoholic liver diseases. The upper limit of normal CDT levels was 80 mg/liter (2 SD above the mean). CDT values exceeding this level were found in more than 80% of Black, Puerto Rican, and Caucasian alcoholics who had consumed greater than or equal to 50 g of alcohol/day for 1 month or longer prior to testing. Puerto Rican alcoholics had higher CDT values than the Black and Caucasian ethnic groups; however, these differences were significant only when compared to the Black population. Of 64 patients with nonalcoholic liver diseases, one individual with chronic active hepatitis (CAH) with an alcohol consumption of 20 g/day, and 10 of 26 subjects with primary biliary cirrhoses (PBC), who claimed to consume either no or only occasional moderate amounts of alcohol, had CDT levels ranging from 81 to 144 mg/liter. Seven of these individuals were in advanced stages of PBC. Total transferrin levels were variable and not significantly different in all subject groups studied. CDT/total transferrin ratios were increased in most patients with abnormal amounts of CDT, and there was a significant correlation between these ratios and CDT levels in all study groups. Serum enzyme parameters as well as red blood cell mean corpuscular volumes did not correlate with CDT values.(ABSTRACT TRUNCATED AT 250 WORDS)