Increased Gamma Globulin Following Immunotherapy with Sipuleucel-T Is Associated with Antigen-Specific Antibody Responses

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1738-1738
Author(s):  
Robert B. Sims ◽  
Mark H. Wener ◽  
Corazon P. dela Rosa ◽  
Lisa R. C. Lin ◽  
Nadeem A. Sheikh

Abstract Abstract 1738 Sipuleucel-T is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated with a recombinant human protein, PAP-GM-CSF (prostatic acid phosphatase [PAP] linked to granulocyte-macrophage colony-stimulating factor [GM-CSF]). It is prepared from cells collected by leukaphereses at Weeks 0, 2, and 4 and infused approximately 3 days following each leukapheresis. In the IMPACT study, 512 patients were randomized (2:1) to sipuleucel-T or control (non-activated autologous PBMCs). Serum samples were collected at Baseline and Weeks 6, 14, and 26, and were analyzed for routine clinical chemistry tests in a comprehensive metabolic panel, which included total protein and albumin. In selected samples, serum protein electrophoresis (SPEP) and densitometry were performed using the Sebia automated electrophoresis system. We observed elevated total protein at Weeks 6 and 14 in sipuleucel-T patients only. At Week 6, 10.0% (28/279) of sipuleucel-T patients with a normal baseline total protein concentration had an elevated total protein concentration (upper limit of normal [ULN] = 7.9 to 8.5 g/dL, depending on age) compared with 0% (0/140) of control patients. At Week 14, 10.4% (19/183) of sipuleucel-T patients with a normal baseline total protein had an elevated total protein compared with 0% (0/86) of control patients. Albumin levels were not elevated at Week 6 following treatment (0.4% ½84 of sipuleucel-T patients with a normal baseline albumin concentration had increases in post-treatment serum albumin), indicating that the changes in total protein were due to elevations in serum globulin. In sipuleucel-T patients, there was a positive correlation between the maximum globulin protein elevations (total protein minus albumin) and the magnitude of antibody titers to PAP-GM-CSF at Week 6 (n = 126; P = 0.001) and Week 14 (n = 85; P = 0.002). Samples from sipuleucel-T patients for whom both a baseline and post-treatment sample were available and who fell within the upper 10th percentile of the total protein change (n = 13) were evaluated by SPEP. All of these patients had increased gamma globulin compared with baseline. Nine patients (69.2%) developed gamma globulin above the upper limit of normal (i.e., > 1.5 g/dL) which was not present at baseline. A correlation between gamma globulin elevations and antibody titers to PAP-GM-CSF in these patients (n = 9) was observed at Week 6 (r = 0.664, P = 0.051). These data demonstrate that elevated gamma globulin levels can develop following treatment with sipuleucel-T and were associated with the development of an antigen-specific humoral response. Disclosures: Sims: Dendreon Corp.: Employment. dela Rosa:Dendreon Corp.: Employment. Lin:Dendreon Corp.: Employment. Sheikh:Dendreon Corp.: Employment.

1993 ◽  
Vol 264 (5) ◽  
pp. H1723-H1726 ◽  
Author(s):  
B. T. Peterson ◽  
R. W. Tate

The standard curve of a typical colorimetric assay for total protein is often nonlinear and dependent on the albumin fraction of the protein standard. We developed a simple mathematical transformation to make the standard curve linear and a computational method to correct for differences in albumin concentrations among the samples. This method uses data from total protein assays on two sets of standards (albumin and gamma globulin) and provides accurate measures of total protein over the full range of albumin fractions. Comparison of this two-standard method with the a method that uses only albumin as a standard shows that this method prevents physiologically significant overestimations in total protein concentration and calculated protein osmotic pressure differences in the lungs.


2019 ◽  
Vol 34 (4) ◽  
pp. 867-872
Author(s):  
Majlinda Ademi ◽  
Icko Gjorgoski ◽  
Ilbert Ademi

Alkaline water is in the focus of scientific interest over the last decade, due to its ability to alkalize the organism as well as its antioxidant effect. The aim of our research is to determine the impact of ionized water by adding enzymatic and non-enzymatic antioxidants, glutathione and vitamin C, during hyperthermic stress, on the concentration of total proteins. The experiment performed on a white laboratory Wistar rats, a female sex, weighing 180-220 g, young rats, divided into three groups of 15 individuals. Oxidative stress was caused by acute hyperthermic exposure at 41˚C. The first group is the control group (KPM), the second group is treated with ionized water (TAM), and the third group with ionized water with added glutathione and vitamin C (TAD). The duration of treatment lasted 21 days. Acute hyperthermic exposure caused a significant difference in total protein concentration between the 7th and 14th day taken as the starting points and the 21st day of treatment, respectively, on the day of hyperthermic exposure of rats. Such a significant difference was observed in the KPM and the TAM group (p <0.001), whereas the TAD group is an exception where no statistically significant difference was observed in the same period (p> 0.05). Animals treated with ionized water on day 14 showed a significantly higher total protein concentration (p <0.01) compared to the group receiving only natural water, which is consistent with the finding obtained by comparison between the KPM and TAD group at 21st day where the difference is also statistically significant (p <0.05). The acute application of the treatment with ionized water, without or in combination with other antioxidants, in the absence of hyperthermic stress does not lead to a significant alteration in protein concentration. The hyperthermic exposure intensifies the production of oxygen radicals and the potential for oxidative modification of proteins and molecules with a protein structure. Individual action of ionized water as well as synergism with the added antioxidants caused a high protective effect on oxidative damage. Because of this, the effect of oxidative cleavage is less pronounced in rats treated with ionized water and antioxidants because they have a stronger antioxidant defense that prevents oxidative modification of proteins and all biomolecules in the body.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ulrica Almhöjd ◽  
Hulya Cevik-Aras ◽  
Niclas Karlsson ◽  
Jin Chuncheng ◽  
Annica Almståhl

Abstract Background To analyse over time changes in stimulated whole saliva regarding total protein, Immunoglobulin A (IgA), and mucin type O-glycans (mostly MUC5B and MUC7) in head and neck cancer patients. Methods 29 dentate patients (20 men and 9 women, 59 ± 8 years) treated with curative radiation therapy and chemotherapy for cancer of the head and neck region were included. The stimulated whole salivary secretion rate was determined and saliva collected at four time-points: at pretreatment, and at 6 months, 1 and 2 years post treatment. The total protein concentration was determined spectrophotometrically by using Bicinchoninic Acid assay and Immunoglobulin A (IgA) by using ELISA technique. Glycosylation pattern of salivary mucins was determined in samples collected pre- and post treatment by using LC/MS electrospray and mucin content quantified using SDS-AgPAGE gels and PAS staining. Results Compared with pretreatment, the total protein concentration was increased already at 6 months post treatment (p < 0.01), and continued to increase up to 2 years post treatment (p < 0.001). During that period no significant changes in IgA concentration was detected. At pretreatment, the output/min of both total protein and IgA was significantly higher than at all time-points post treatment. Saliva from the cancer patients showed a low abundance/no detectable MUC7, while the MUC5B level remained, compared to saliva from a healthy control. The glycomic analysis showed that the percentage of core 2 O-glycans was increased as core 1, 3 and 4 O-glycans were decreased. The level of sialylation was higher at 6 months post treatment, while sulfation was lower. Conclusion A decreased output per minute of proteins at decreased salivary secretion rate, as well as reduced sulfation of MUC5B at 6 months post treatment tended to correlate with the patients’ experience of sticky saliva and oral dryness. At 2 years post treatment, the decreased amount of IgA combined with a lowered salivary secretion rate indicate a reduced oral defense with increased risk of oral infections.


1987 ◽  
Vol 33 (3) ◽  
pp. 411-413 ◽  
Author(s):  
S H Zlotkin ◽  
C W Casselman

Abstract We measured the concentrations of total protein and albumin in sera of 281 well-fed premature infants, gestational ages 22-36 weeks, and calculated reference values from the 10th to 90th percentiles. The mean serum albumin concentration (27.6 +/- 4.4 g/L, mean +/- SD) and total protein concentration (49.2 +/- 6.7 g/L) at a postnatal age of 14.5 days were lower than reference values for full-term infants. We detected a significant positive correlation between albumin concentration and gestational age (r = 0.34, p less than 0.01) and total protein concentration and gestational age (r = 0.43, p less than 0.01). Even though albumin values were low, generalized edema was not present. We conclude that values for total protein and albumin in the preterm infant are lower than in the full-term infant but are an expected physiological response to premature birth.


2014 ◽  
Vol 27 (1) ◽  
pp. 253-257 ◽  
Author(s):  
Patrick Marcel Seumo Tchekwagep ◽  
Charles Péguy Nanseu-Njiki ◽  
Emmanuel Ngameni ◽  
Ravi Danielsson ◽  
Thomas Arnebrant ◽  
...  

2015 ◽  
Vol 6 (1) ◽  
pp. 17-22
Author(s):  
A. I. Shevtsova ◽  
G. A. Ushakova

There is no standard as to treatment of anthracycline chemotherapy complications. The reduction of cytotoxic drugs toxicity without weakening of their antitumor action remains relevant. The extracellular matrix which key component is fibronectin is present in all tissues and it continuously undergoes controlled remodeling. So, the purpose of our work was to study the level of fibronectin in the experimental model of doxorubicin-induced cardiomyopathy and effects of this cytostatic and its co-administration with antioxidants of different nature.The level of fibronectin was measured by ELISA using monospecific antibodies against fibronectin (Sigma, USA), secondary anti-IgG labeled with horseradish peroxidase (Sigma, USA) and fibronectin standard (Sigma, USA). The study was conducted on Wistar male rats with weight of 210 ± 50 g which were divided into 4 groups by 8 animals in each group: 1 – control, rats receiving saline i/p; 2 – doxorubicin 1 mg/kg i/p once a week during 4 weeks; 3 – doxorubicin by the same scheme plus 1% 2-oxoglutarate in drinking water during 4 weeks;4 – doxorubicin by the same scheme and korvitin injection 30 min before doxorubicin application once a week during 4 weeks. Obtained data indicate the effect of doxorubicin to decrease in index mass heart in 38% of animals compared to control animals; decrease in total protein concentration by 8% (Р < 0,05) and increase of the level of fibronectin by 67% (P < 0,001) in blood plasma of rats and decrease in the level of fibronectin in the heart extract by 19% (Р < 0,05) under development of doxorubicin-induced cardiotoxicity. Increased fibronectin concentration in blood plasma had strong correlation with decreased total protein concentration in blood (r=0,80) and heart extract (r=0,59) in rats with doxorubicin-induced cardiomiophaty indicating the sensitive reaction of fibronectin to development of metabolic disorders under doxorubicin influence. 


1964 ◽  
Vol 19 (2) ◽  
pp. 292-296 ◽  
Author(s):  
Irene R. Held ◽  
Smith Freeman

The binding of calcium to human plasma albumin, alpha, beta, and gamma globulins was studied with the aid of an ultracentrifuge. The amount of calcium bound to these separated proteins was determined in solutions with electrolyte concentrations and pH within physiological ranges. The total calcium concentration was 2.35–2.90 mm/liter H2O and the total protein concentration was 3.91–4.29 g/100 ml H2O. In these solutions no significant differences were found for the binding of calcium (expressed as mm Ca++ bound per gram protein) by albumin, alpha, and beta globulins; the average values obtained were, respectively, 0.016, 0.018, and 0.023. Significantly less calcium was bound by gamma globulin; 0.009 mm/gram. The pH was varied between 7.200–7.550 and the sodium chloride concentration between 114–157 mEq Na per liter. These changes did not measurably affect the amount of calcium bound to albumin. protein-bound calcium; ultracentrifugation and determination of protein-bound calcium; plasma globulin-bound calcium; plasma albumin-bound calcium Submitted on July 2, 1963


1983 ◽  
Vol 29 (1) ◽  
pp. 126-129 ◽  
Author(s):  
P R Finley ◽  
R J Williams

Abstract We evaluated a rate colorimetric method (Beckman) for measuring total protein in cerebrospinal fluid. The automated instrument we used was Beckman's ASTRA TM. A 100-microL sample of spinal fluid is introduced into the biuret reagent in the reaction cell and the increase in absorbance at 545 nm is monitored for 20.5 s. Solid-state circuits determine the rate of alkaline biuret-protein chelate formation, which is directly proportional to the total protein concentration in the sample. The linear range of measurement is 120 to 7500 mg/L. Day-to-day precision (CV) over the range of 150 to 1200 mg/L ranged from 15.2 to 2.3%. The method was unaffected by radical alteration of the albumin/globulin ratio, but there is a positive interference in the presence of hemoglobin, a suppression in the presence of bilirubin, and no effect by xanthochromia. The method is precise, accurate, rapid, and convenient. The method was compared with the trichloroacetic acid method as performed on the Du Pont aca III, giving a correlation coefficient (r2) of 0.9693. The method is precise, accurate, rapid, and convenient.


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