[Possibilities of differentiation of antinuclear antibodies].

Science.gov (United States)

Müller, W; Rosenthal, M; Stojan, B

1975-10-15

Antinuclear antibodies can give diagnostic informations according to their titre values, the belonging to different classes of immune globulins and on the basis of different patterns of immunofluorescence connection. The determination of granulocyte-specific antibodies which frequently appear in progressive chronic polyarthritis further contributes to the differential-diagnostic classification of diseases of the connective tissue. An antibody against extractable nuclear antigen is specific for the so-called mixed connective tissue disease, an antimitochondrial antibody for the pseudo-LE-syndrome. Moreover, the own examinations resulted in a particularly high and frequent ability of complement fixation of the antinuclear factors in systematic lupus erythematosus and sclerodermy. In contrast to this in the progressive chronic polyarthritis the complement fixation was clearly more insignificant.

Antibody informatics for drug discovery

DEFF Research Database (Denmark)

Shirai, Hiroki; Prades, Catherine; Vita, Randi

2014-01-01

to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: a study on anti-CarP antibodies as an example.

Science.gov (United States)

Boeters, Debbie M; Trouw, Leendert A; van der Helm-van Mil, Annette H M; van Steenbergen, Hanna W

2018-05-03

The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA). There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF. Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2-2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3-3.7). For the 2010-UA patients, anti-CarP antibodies were associated with progression to RA; however, they were not when a correction was made for the presence of ACPA and RF (OR 0.8, 95% CI 0.3-2.1). Our finding that anti-CarP antibodies have no additional value when RA is defined according to the 2010 criteria might

Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.

Science.gov (United States)

Iwata, Naoko; Iwama, Shintaro; Sugimura, Yoshihisa; Yasuda, Yoshinori; Nakashima, Kohtaro; Takeuchi, Seiji; Hagiwara, Daisuke; Ito, Yoshihiro; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Caturegli, Patrizio; Koike, Teruhiko; Oshida, Yoshiharu; Arima, Hiroshi

2017-06-01

IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence. APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases. Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C

Science.gov (United States)

Ezzikouri, Sayeh; Kimura, Kiminori; Sunagozaka, Hajime; Kaneko, Shuichi; Inoue, Kazuaki; Nishimura, Tomohiro; Hishima, Tsunekazu; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

2015-01-01

Background New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC). Methods Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay. Results The serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens. Conclusions DHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC. PMID:26288822

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

Energy Technology Data Exchange (ETDEWEB)

Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

2014-11-07

Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

International Nuclear Information System (INIS)

Kim, Su Jin; Chang, Suhwan; Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho; Chung, Young-Hwa; Park, Young Woo; Koh, Sang Seok

2014-01-01

Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31 + vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models

Clinical spectrum and diagnostic value of antibodies against the potassium channel-related protein complex☆

Science.gov (United States)

Montojo, M.T.; Petit-Pedrol, M.; Graus, F.; Dalmau, J.

2016-01-01

Introduction Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes. Review summary In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed. Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain. Conclusions The discovery of antigens such as LGI1 and Caspr2 has resulted in a clinical and molecular definition of the broad group of diseases previously attributed to antibodies against VGKC. Considering the literature that describes the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we propose a practical

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study

NARCIS (Netherlands)

Eysink, P. E.; de Jong, M. H.; Bindels, P. J.; Scharp-van der Linden, V. T.; de Groot, C. J.; Stapel, S. O.; Aalberse, R. C.

1999-01-01

Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat

Tumor detection using radiolabeled monoclonal antibodies

International Nuclear Information System (INIS)

Moldofsky, P.J.; Powe, J.; Hammond, N.D.

1987-01-01

Radioisotope conjugated to monoclonal antibody products has been used for imaging tumors targeted by the antibody. As imaging progresses, new sets of procedural and technical questions arise. In this chapter, we discuss several current problems in imaging tumor with radiolabeled monoclonal antibody. These include (1) methods for selection of specific antibody and, once the particular antibody is selected, which fragment form is to be used; (2) imaging procedures: what are the optimum imaging parameters, such as optimum time for imaging after administration of tracer and considerations regarding background subtraction; and (3) noninvasive quantitative techniques: quantitation of localization of antibody indirectly from quantitative information in the images.100 references

Antiplatelet antibody may cause delayed transfusion-related acute lung injury

Directory of Open Access Journals (Sweden)

Torii Y

2011-09-01

Full Text Available Yoshitaro Torii1, Toshiki Shimizu1, Takashi Yokoi1, Hiroyuki Sugimoto1, Yuichi Katashiba1, Ryotaro Ozasa1, Shinya Fujita1, Yasushi Adachi2, Masahiko Maki3, Shosaku Nomura11The First Department of Internal Medicine, Kansai Medical University, Osaka, 2Department of Clinical Pathology, Toyooka Hospital, Hyogo, 3First Department of Pathology, Kansai Medical University, Osaka, JapanAbstract: A 61-year-old woman with lung cancer developed delayed transfusion-related acute lung injury (TRALI syndrome after transfusion of plasma- and leukoreduced red blood cells (RBCs for gastrointestinal bleeding due to intestinal metastasis. Acute lung injury (ALI recurred 31 days after the first ALI episode. Both ALI episodes occurred 48 hours after transfusion. Laboratory examinations revealed the presence of various antileukocyte antibodies including antiplatelet antibody in the recipient's serum but not in the donors' serum. The authors speculate that antiplatelet antibodies can have an inhibitory effect in the recipient, which can modulate the bona fide procedure of ALI and lead to a delay in the onset of ALI. This case illustrates the crucial role of a recipient's platelets in the development of TRALI.Keywords: delayed TRALI syndrome, recurrence, anti-platelet antibody

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis.

Science.gov (United States)

Peeler, Crandall E; De Lott, Lindsey B; Nagia, Lina; Lemos, Joao; Eggenberger, Eric R; Cornblath, Wayne T

2015-10-01

The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the

Clinical spectrum and diagnostic value of antibodies against the potassium channel related protein complex.

Science.gov (United States)

Montojo, M T; Petit-Pedrol, M; Graus, F; Dalmau, J

2015-06-01

Antibodies against a protein complex that includes voltage-gated potassium channels (VGKC) have been reported in patients with limbic encephalitis, peripheral nerve hyperexcitability, Morvan's syndrome, and a large variety of neurological syndromes. In this article, a review is presented of the syndromes associated with antibodies against VGKC-related proteins and the main antigens of this protein complex, the proteins LGI1 (leucine rich glioma inactivated protein 1) and Caspr2 (contactin-associated protein-like 2). The conceptual problems and clinical implications of the description of antibodies against VGKC-related proteins other than LGI1 and Caspr2 are also discussed. Although initial studies indicated the occurrence of antibodies against VGKC, recent investigations have shown that the main antigens are a neuronal secreted protein known as LGI1 which modulates synaptic excitability, and a protein called Caspr2 located on the cell surface and processes of neurons of different brain regions, and at the juxtaparanodal region of myelinated axons. While antibodies against LGI1 preferentially associate with classical limbic encephalitis, antibodies against Caspr2 associate with a wider spectrum of symptoms, including Morvan's syndrome, peripheral nerve hyperexcitability or neuromyotonia, and limbic or more extensive encephalitis. In addition there are reports of patients with antibodies against VGKC-related proteins that are different from LGI1 or Caspr2. In these cases, the identity and location of the antigens are unknown, the syndrome association is not specific, and the response to treatment uncertain. The discovery of antigens such as LGI1 and Caspr2 has resulted in a clinical and molecular definition of the broad group of diseases previously attributed to antibodies against VGKC. Considering the literature that describes the presence of antibodies against VGKC other than LGI1 and Caspr2 proteins, we propose a practical algorithm for the diagnosis and treatment

Antiphospholipid Antibody Syndrome Presenting with Hemichorea

Directory of Open Access Journals (Sweden)

Yezenash Ayalew

2012-01-01

Full Text Available A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120 and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

Rapid isolation of antibody from a synthetic human antibody library by repeated fluorescence-activated cell sorting (FACS.

Directory of Open Access Journals (Sweden)

Sung Sun Yim

Full Text Available Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS. First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼ 10(6. These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

Energy Technology Data Exchange (ETDEWEB)

Wahl, R.L.; Piko, C.R.; Beers, B.A.; Geatti, O.; Johnson, J.; Sherman, P. (Michigan Univ., Ann Arbor, MI (USA). Dept. of Internal Medicine)

1989-01-01

The authors evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times. The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +- 5.1%) than for those perfused at 24h post i.v. antibody injection (32.9 +- 2.9%). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively by computer image analysis enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor. These studies show that much background antibody radioactivity can be removed using whole-body perfusion with saline, that the decline in whole body activity is larger with 4 than 24h perfusion and that tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.

THE EFFECT OF SALICYLATES ON THE PRECIPITATION OF ANTIGEN WITH ANTIBODY.

Science.gov (United States)

Coburn, A F; Kapp, E M

1943-02-01

1. Sodium salicylate modifies the precipitation of normal rabbit serum protein by sodium tungstate, and partially inhibits the precipitation of horse serum euglobulin by rabbit antiserum. Sodium salicylate added to a system containing crystalline egg albumin and its antibody partly prevents the formation of precipitate, the degree of inhibition being related to the concentration of salicylate. 2. Precipitation in the equivalence zone is more readily prevented by salicylate than precipitation in the region of antibody excess, the immune system becoming progressively less sensitive to the action of salicylate as the excess of antibody becomes larger. 3. Formed precipitates were partly dissolved following resuspension in the presence of salicylate. 4. The salicylate effect on immune precipitation is reversible, and appears to be due to inactivation of antibody. 5. Salicylate was more effective in preventing specific precipitation than other anions of a lyotropic series tested.

Monoclonal antibodies in oncology

International Nuclear Information System (INIS)

Chan, S.Y.T.; Sikora, K.

1986-01-01

Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. (Auth.)

Radiographic progression of rheumatoid arthritis related to some clinical and laboratory parameters

International Nuclear Information System (INIS)

Carvalho, A. de; Graudal, H.

1980-01-01

In 188 patients followed for 3 to 12 years, the radiologic course of rheumatoid arthritis was assessed in 20 joint groups. A severe course in most joints was related to the presence of rheumatoid factor and to high values of the ESR. Granulocyte-specific antinuclear antibodies were related to a severe course in most joints. The presence of nodules, the Rose-Waaler titre and the presence of organ non-specific antinuclear antibodies were generally unrelated to the course of the disease. (Auth.)

Comparative tumour localization properties of radiolabelled monoclonal antibody preparations of defined immunoreactivities

International Nuclear Information System (INIS)

Pimm, M.V.; Baldwin, R.W.

1987-01-01

The immunoreactive fraction of an anti-CEA monoclonal antibody preparation has been progressively decreased by the addition of increasing proportions of impurity in the form of immunologically inert mouse immunoglobulin. Following radioiodination, the immunoreactive fractions of the preparations were determined and their localization in a human tumour xenograft in nude mice was assessed. There was a progressive decline in tumour localization, from tumour to blood ratios of 2:1 with unadulterated antibody to 0.6:1 with preparations only 15% with respect to the initial antibody. These findings demonstrate that the immunoreactive fraction of monoclonal antibody preparations is a major limiting factor in tumour localization and this has implications for experimental and clinical applications of monoclonal antibodies. (orig.)

LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes

Science.gov (United States)

Binks, Sophie N M; Klein, Christopher J; Waters, Patrick; Pittock, Sean J; Irani, Sarosh R

2018-01-01

Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity. In this review, we describe and compare the clinical features associated with pathogenic LGI1 and CASPR2 antibodies, illustrate emerging laboratory techniques for antibody determination and describe the immunological mechanisms that may mediate antibody-induced pathology. We highlight marked clinical overlaps between patients with either LGI1 or CASPR2 antibodies that include frequent focal seizures, prominent amnesia, dysautonomia, neuromyotonia and neuropathic pain. Although occurring at differing rates, these commonalities are striking and only faciobrachial dystonic seizures reliably differentiate these two conditions. Furthermore, the coexistence of both LGI1 and CASPR2 antibodies in an individual occurs surprisingly frequently. Patients with either antibody respond well to immunotherapies, although systematic studies are required to determine the magnitude of the effect beyond placebo. Finally, data have suggested that CASPR2 and LGI1 modulation via genetic or autoimmune mechanisms may share common intermediate molecules. Taken together, the biochemical distinction of antigenic targets has led to important clinical advances for patient care. However, the striking syndrome similarities, coexistence of two otherwise rare antibodies and molecular insights suggest the VGKC complex may yet be a common functional effector of antibody action. Hence, we argue for a molecular evolution alongside a

GAD65 antibodies among Greenland Inuit and its relation to glucose intolerance

DEFF Research Database (Denmark)

Pedersen, Michael Lynge; Bjerregaard, Peter; Jørgensen, Marit Eika

2014-01-01

The aim of this study was to compare the prevalence of circulating Glutamin-Acid-decarboxylase 65 antibodies in a sample of Greenlanders (Inuit) with clinically verified diabetes with samples of participants from a population survey. The study population included participants with known diabetes.......3 % and less than 1 % among Greenlanders without diabetes (p = 0.001). The prevalence of circulating Glutamin-Acid-decarboxylase 65 antibodies among Greenlanders with and without diabetes is relatively low in a global perspective in accordance with one former study among Inuit. Autoimmune diabetes seems...

A pharmacology guided approach for setting limits on product-related impurities for bispecific antibody manufacturing.

Science.gov (United States)

Rajan, Sharmila; Sonoda, Junichiro; Tully, Timothy; Williams, Ambrose J; Yang, Feng; Macchi, Frank; Hudson, Terry; Chen, Mark Z; Liu, Shannon; Valle, Nicole; Cowan, Kyra; Gelzleichter, Thomas

2018-04-13

bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product. The aim of the current study was to determine acceptable levels of product-related impurities for bFKB1. To determine the tolerable levels of these impurities, we dosed obese mice with bFKB1 enriched with various levels of either HMW impurities or anti-FGFR1-related impurities, and measured biomarkers for KLB-independent FGFR1 signaling. Here, we show that product-related impurities of bFKB1, in particular, high molecular weight (HMW) impurities and anti-FGFR1-related impurities, when purposefully enriched, stimulate FGFR1 in a KLB-independent manner. By taking this approach, the tolerable levels of product-related impurities were successfully determined. Our study demonstrates a general pharmacology-guided approach to setting a product specification for a bispecific antibody whose homomultimer-related impurities could lead to undesired biological effects. Copyright © 2018. Published by Elsevier Inc.

Atypical presentation of probable Creutzfeldt-Jakob disease associated with anti-Zic4 antibody: Literature review of neuronal antibodies in Creutzfeldt-Jakob disease.

Science.gov (United States)

Salazar, Richard

2018-05-01

Sporadic Creutzfeldt-Jakob disease is a prion disease characterized by rapidly progressive dementia, ataxia and myoclonus. Atypical phenotype masquerading as stroke, movement disorders or autoimmune encephalitis have been described. Here, I report a probable case of sCJD with an atypical presentation associated with anti-Zic4 antibody and review the literature of neuronal antibodies in CJD. A 70 year-old gentleman is admitted with a 2-month history of recurrent stroke-like symptoms associated with behavioral disturbances, gait ataxia and rapidly progressive dementia. His initial examination demonstrated akinetic mutism, diffuse rigidity, dysautononia, and Cheyne-Stokes respiration. Over the following weeks his condition progressed to profound coma. A comprehensive infectious, metabolic, inflammatory and autoimmune work-up yielded negative results. Empiric immunosuppressive therapy ensued. He expired three months after symptoms onset. Autopsy was not performed. After his demise, prion tests came back abnormal for elevated 14-3-3 protein, total tau and positive RTQuIC. Later on, anti-Zic4 antibodies were found in serum. This case underscores the importance of a high index of suspicion for CJD even in case of atypical features or the concurrence of neuronal antibodies. Further larger prospective studies on the prevalence of these neuronal antibodies in CJD and the contribution of these autoantibodies to disease pathophysiology are necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression

DEFF Research Database (Denmark)

Tsimikas, Sotirios; Miyanohara, Atsushi; Hartvigsen, Karsten

2011-01-01

We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibod...... antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis....

Antibodies to watch in 2014.

Science.gov (United States)

Reichert, Janice M

2014-01-01

Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.

Recent progress of diagnostic and therapeutic approach to cancers using polyclonal or monoclonal antibodies

International Nuclear Information System (INIS)

Koji, Toshihiko

1982-01-01

Among the major topics of interest in cancer immunology, immunodiagnosis and immunotherapy with the antibodies are summarized historically and prospectively. The concept of injecting anti-tumor cell antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials have been achieved with human tumors using specific or nonspecific tumor-localizing antibodies diagnostically or therapeutically. In 1970's, successes in immunodiagnosis with the antibodies to oncofetal proteins also have been reported. Recently, there are numerous papers dealed with a series of external scanning or serotherapeutic trials by the use of monoclonal antibodies that bind selectively to tumor cells. Various relevant problems with them are discussed. (author)

Quantitative relationship between antibody affinity and antibody avidity

International Nuclear Information System (INIS)

Griswold, W.R.

1987-01-01

The relationship between antibody avidity, measured by the dissociation of the antigen-antibody bond in antigen excess, and antibody affinity was studied. Complexes of radiolabelled antigen and antibody of known affinity were prepared in vitro and allowed to stand for seven days to reach equilibrium. Then nonlabelled antigen in one hundred fold excess was added to dissociate the complexes. After an appropriate incubation the fraction of antigen bound to antibody was measured by the ammonium sulfate precipitation method. The dissociation index was the fraction bound in the experimental sample divided by the fraction bound in the control. The correlation coefficient between the dissociation index and the antibody binding constant was 0.92 for early dissociation and 0.98 for late dissociation. The regression equation relating the binding constant to the dissociation index was K = 6.4(DI) + 6.25, where DI is the late dissociation index and K is the logarithm to the base 10 of the binding constant. There is a high correlation between avidity and affinity of antibody. Antibody affinity can be estimated from avidity data. The stability of antigen-antibody complexes can be predicted from antibody affinity

The development of AIDS or AIDS-related conditions in a cohort of HIV antibody-positive homosexual men during a 3-year follow-up period

DEFF Research Database (Denmark)

Pedersen, C; Kolby, P; Sindrup, J

1989-01-01

One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses...... with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy. When adjusted to the probable year of infection, these results are in accordance with previous cohort studies. It is concluded that most, or all, subjects seropositive for HIV will develop......, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes less than 0.5 x 10(9) l-1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes less than 0.3 x 10 l-1 and elevated serum level of IgA were significantly associated...

Bispecific antibodies targeting human CD73

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen.......The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen....

Natural Antibodies Related to Energy Balance in Early Lactation Dairy Cows

NARCIS (Netherlands)

Knegsel, van A.T.M.; Vries Reilingh, de G.; Meulenberg, S.; Brand, van den H.; Dijkstra, J.; Kemp, B.; Parmentier, H.K.

2007-01-01

The objectives of this study were to determine the presence of natural antibodies (NAb) in plasma and milk of individual dairy cows and to study the relation between NAb concentrations and energy balance (EB) and dietary energy source. Cows (n = 76) were fed a mainly glucogenic, lipogenic, or a

LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes.

Science.gov (United States)

Binks, Sophie N M; Klein, Christopher J; Waters, Patrick; Pittock, Sean J; Irani, Sarosh R

2018-05-01

Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity. In this review, we describe and compare the clinical features associated with pathogenic LGI1 and CASPR2 antibodies, illustrate emerging laboratory techniques for antibody determination and describe the immunological mechanisms that may mediate antibody-induced pathology. We highlight marked clinical overlaps between patients with either LGI1 or CASPR2 antibodies that include frequent focal seizures, prominent amnesia, dysautonomia, neuromyotonia and neuropathic pain. Although occurring at differing rates, these commonalities are striking and only faciobrachial dystonic seizures reliably differentiate these two conditions. Furthermore, the coexistence of both LGI1 and CASPR2 antibodies in an individual occurs surprisingly frequently. Patients with either antibody respond well to immunotherapies, although systematic studies are required to determine the magnitude of the effect beyond placebo. Finally, data have suggested that CASPR2 and LGI1 modulation via genetic or autoimmune mechanisms may share common intermediate molecules. Taken together, the biochemical distinction of antigenic targets has led to important clinical advances for patient care. However, the striking syndrome similarities, coexistence of two otherwise rare antibodies and molecular insights suggest the VGKC complex may yet be a common functional effector of antibody action. Hence, we argue for a molecular evolution alongside a

Antibodies to elastin peptides in sera of Belgian Draught horses with chronic progressive lymphoedema.

Science.gov (United States)

van Brantegem, L; de Cock, H E V; Affolter, V K; Duchateau, L; Hoogewijs, M K; Govaere, J; Ferraro, G L; Ducatelle, R

2007-09-01

Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge. Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown. An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83). Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions. CPL in draught horses is associated with an increase of serum AEAbs. Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.

The antibody approach of labeling blood cells

International Nuclear Information System (INIS)

Srivastava, S.C.

1992-01-01

Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated

The antibody approach of labeling blood cells

International Nuclear Information System (INIS)

Srivastava, S.C.

1991-01-01

Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated

The antibody approach of labeling blood cells

Energy Technology Data Exchange (ETDEWEB)

Srivastava, S.C.

1991-12-31

Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

The antibody approach of labeling blood cells

Energy Technology Data Exchange (ETDEWEB)

Srivastava, S.C.

1991-01-01

Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

The antibody approach of labeling blood cells

Energy Technology Data Exchange (ETDEWEB)

Srivastava, S.C.

1992-12-31

Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

Towards On-site Pathogen Detection Using Antibody-based Sensors

DEFF Research Database (Denmark)

Skottrup, Peter Durand; Nicolaisen, Mogens; Justesen, Annemarie Fejer

2008-01-01

In this paper the recent progress within biosensors for plant pathogen detection will be reviewed. Bio-recognition layers on sensors can be designed in various ways, however the most popular approach is to immobilise antibodies for specific capture of analytes. Focus will be put on antibody surfa...

Antibody-Based Immunotoxins for the Treatment of Cancer

Directory of Open Access Journals (Sweden)

Nurit Becker

2012-05-01

Full Text Available Antibody-based immunotoxins comprise an important group in targeted cancer therapeutics. These chimeric proteins are a form of biological guided missiles that combine a targeting moiety with a potent effector molecule. The targeting moiety is mostly a monoclonal antibody (MAb or a recombinant antibody-based fragment that confers target specificity to the immunotoxin. The effector domain is a potent protein toxin of bacterial or plant origin, which, following binding to the target cells, undergoes internalization and causes cell death. Over time and following research progression, immunotoxins become better fitted to their purpose, losing immunogenic fragments and non-specific targeting moieties. Many immunotoxins have gone through clinical evaluation. Some of these have been shown to be active and work is progressing with them in the form of further clinical trials. Others, mostly developed in the previous century, failed to generate a response in patients, or even caused undesired side effects. This article reviews the antibody and protein-toxin based immunotoxins that were clinically evaluated up to the present day.

[International classification of various types of monoclonal antibodies].

Science.gov (United States)

Scheen, A J

2009-01-01

Significant advances in the development of monoclonal antibodies ("mabs") have been acknowledged during the last two decades. Successive developments led to the marketing of murine antibodies ("o-mab" first, followed by chimeric antibodies ("xi-mab"), humanised antibodies ("zu-mab") and, finally, human monoclonal antibodies ("u-mab"). In order to facilitate the distinction between the various monoclonal antibodies used in clinical practice, an international nomenclature has been proposed with the use of a specific suffix corresponding to the origine/source of "mabs" preceded by an infix referring to the medicine's target. The efforts in developing new types of monoclonal antibodies aimed at improving their pharmacokinetics (longer half-life), pharmacodynamics (better efficacy because of stronger affinity to human receptor), and safety profile (less antigenic and immunogenic reactions). These progresses could be obtained thanks to the remarkable development of molecular biotechnology.

Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane

International Nuclear Information System (INIS)

Madaio, M.P.; Salant, D.J.; Adler, S.; Darby, C.; Couser, W.G.

1984-01-01

Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. The authors examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4-8.5) and anionic (pI 4.2-6.8) fractions, which were radiolabelled with 131 I and 125 I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r . 0.95, r . 0.97) and delivery of antibody (r . 0.98, r . 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P less than 0.001). The authors conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies

[Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases].

Science.gov (United States)

Watanabe, Osamu

2016-09-01

Voltage-gated potassium channel (VGKC) complex antibodies are auto-antibodies, initially identified in acquired neuromyotonia (aNMT; Isaacs' syndrome), which cause muscle cramps and difficulty in opening the palm of the hands. Subsequently, these antibodies were found in patients presenting with aNMT along with psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) patient with prominent amnesia and frequent seizures. Typical LE cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures (FBDS). The VGKC complex is a group of proteins that are strongly associated in situ and after extraction in the mild detergent digitonin. Recent studies indicated that the VGKC complex antibodies are mainly directed toward associated proteins (for example LGI1, Caspr2) that complex with VGKCs themselves. Patients with aNMT or MoS are most likely to have Caspr2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. We systematically identified and quantified autoantibodies in patient sera with VGKC-complex antibody associated encephalopathy and showed the relationship between individual antibodies and patient's symptoms. Furthermore, we revealed how autoantibodies disrupt the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, reducing the synaptic AMPA receptors.

Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire.

Science.gov (United States)

Liu, Ju; Li, Ruihua; Liu, Kun; Li, Liangliang; Zai, Xiaodong; Chi, Xiangyang; Fu, Ling; Xu, Junjie; Chen, Wei

2016-04-22

High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies. Copyright © 2016 Elsevier Inc. All rights reserved.

Case definition for progressive multifocal leukoencephalopathy following treatment with monoclonal antibodies.

Science.gov (United States)

Mentzer, Dirk; Prestel, Jürgen; Adams, Ortwin; Gold, Ralf; Hartung, Hans-Peter; Hengel, Hartmut; Kieseier, Bernd C; Ludwig, Wolf-Dieter; Keller-Stanislawski, Brigitte

2012-09-01

Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for PML is a prerequisite for a thorough assessment of PML. A working group was established to develop a standardised case definition for PML which permits data comparability across clinical trials, postauthorisation safety studies and passive postmarketing surveillance. The case definition is designed to define levels of diagnostic certainty of reported PML cases following treatment with MABs. It was subsequently used to categorise retrospectively suspected PML cases from Germany reported to the Paul-Ehrlich-Institute as the responsible national competent authority. The algorithm of the case definition is based on clinical symptoms, PCR for JC virus DNA in cerebrospinal fluid, brain MRI, and brain biopsy/autopsy. The case definition was applied to 119 suspected cases of PML following treatment with MABs and is considered to be helpful for case ascertainment of suspected PML cases for various MABs covering a broad spectrum of indications. Even if the available information is not yet complete, the case definition provides a level of diagnostic certainty. The proposed case definition permits data comparability among different medicinal products and among active as well as passive surveillance settings. It may form a basis for meaningful risk analysis and communication for regulators and healthcare professionals.

Applications of recombinant antibodies in plant pathology.

Science.gov (United States)

Ziegler, Angelika; Torrance, Lesley

2002-09-01

Summary Advances in molecular biology have made it possible to produce antibody fragments comprising the binding domains of antibody molecules in diverse heterologous systems, such as Escherichia coli, insect cells, or plants. Antibody fragments specific for a wide range of antigens, including plant pathogens, have been obtained by cloning V-genes from lymphoid tissue, or by selection from large naive phage display libraries, thus avoiding the need for immunization. The antibody fragments have been expressed as fusion proteins to create different functional molecules, and fully recombinant assays have been devised to detect plant viruses. The defined binding properties and unlimited cheap supply of antibody fusion proteins make them useful components of standardized immunoassays. The expression of antibody fragments in plants was shown to confer resistance to several plant pathogens. However, the antibodies usually only slowed the progress of infection and durable 'plantibody' resistance has yet to be demonstrated. In future, it is anticipated that antibody fragments from large libraries will be essential tools in high-throughput approaches to post-genomics research, such as the assignment of gene function, characterization of spatio-temporal patterns of protein expression, and elucidation of protein-protein interactions.

Oligopeptide-based enzyme immunoassay for ovine lentivirus antibody detection.

OpenAIRE

Kwang, J; Torres, J V

1994-01-01

Ovine progressive pneumonia virus (OPPV) is a lentivirus which causes a progressive disease in sheep. Immunodominant epitopes have been identified in the envelope gp40 glycoprotein. Synthetic peptides representing these regions are able to detect the presence of OPPV antibodies in 96% of infected sheep.

Monoclonal antibodies in oncology. Review article

Energy Technology Data Exchange (ETDEWEB)

Chan, S Y.T.; Sikora, K

1986-05-01

Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. 69 refs.; 7 figs.; 3 tabs.

Chemoradiotherapy of cancer using boronated monoclonal antibodies. Progress report, December 1, 1982-November 30, 1983

International Nuclear Information System (INIS)

Soloway, A.H.

1984-01-01

The feasibility was established of using antibodies for the delivery of 10 B. Problems faced included 1) preservation of antibody activity following boronation, 2) antigenic receptor site density of the target cells, and 3) delivery of a critical number of 10 B atoms per cell. The linkage of a heavily boronated polymeric species to antibody by means of a single functional group allow for the delivery of a large number 10 B atoms per antibody molecule without a significant reduction in affinity. Both the polyclonally derived anti-thymocyte globulin (ATG) and the monoclonal anti-colorectal carcinoma antibody (17-1A) recognize antigens that are expressed with a density of approximately 10 6 epitopes per cell. The major concept that we advance is that just as effective cancer chemotherapy is based on the use of a combination of drugs, similarly a combination of compounds could be employed to deliver the requisite amount of 10 B to tumor target cells. This could include compounds such as Na 2 B 12 H 11 Sh together with boronated antibodies directed against tumor associated antigens. (DT)

Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

Directory of Open Access Journals (Sweden)

Mayada Ali Abdalla

2018-01-01

Conclusion: Anti-NCS antibodies could play a role in the pathogenesis of SLE and is related to disease activity. Its association with anti-dsDNA antibodies and its presence in those with negative anti-ds DNA may aid in the diagnosis of SLE.

Analysis of the relations between allergen specific LgG antibody and allergic dermatosis of 14 kinds foods

Directory of Open Access Journals (Sweden)

Yin’e Hu

2015-01-01

Full Text Available To use food-specific IgG antibody detection to explore its application in the allergy dermatoses. 181 patients were included from January 2014 to September 2014. Fourteen food-specific IgG antibodies were detected by ELISA. The positive rates of IgG antibody of the patient group and the healthy group were significantly different. The positive rates of IgG antibody of egg, milk, shrimp and crab took a large proportion in three groups of patients with three kinds of allergy dermatoses of urticaria, eczema and allergic dermatitis, the proportion of which was respectively 70.2%, 77.8% and 71.7%. There was mild and moderate intolerance of food in the allergic dermatitis group while there was no distribution difference of food intolerance in urticaria group and eczema group. Among urticaria and allergic dermatitis patients with positive antibody, the positive rate of children was significantly higher than that of adults while there was no significant difference between children and adults among eczema patients with positive antibody. Allergy dermatoses are closely related to food-specific IgG antibody and the allergy dermatoses patients have a high incidence rate of food intolerance; detecting IgG antibody in patients is of great significance for the diagnosis and treatment of allergy dermatoses.

Arrayed antibody library technology for therapeutic biologic discovery.

Science.gov (United States)

Bentley, Cornelia A; Bazirgan, Omar A; Graziano, James J; Holmes, Evan M; Smider, Vaughn V

2013-03-15

Traditional immunization and display antibody discovery methods rely on competitive selection amongst a pool of antibodies to identify a lead. While this approach has led to many successful therapeutic antibodies, targets have been limited to proteins which are easily purified. In addition, selection driven discovery has produced a narrow range of antibody functionalities focused on high affinity antagonism. We review the current progress in developing arrayed protein libraries for screening-based, rather than selection-based, discovery. These single molecule per microtiter well libraries have been screened in multiplex formats against both purified antigens and directly against targets expressed on the cell surface. This facilitates the discovery of antibodies against therapeutically interesting targets (GPCRs, ion channels, and other multispanning membrane proteins) and epitopes that have been considered poorly accessible to conventional discovery methods. Copyright © 2013. Published by Elsevier Inc.

Schistosome infection intensity is inversely related to auto-reactive antibody levels.

Directory of Open Access Journals (Sweden)

Francisca Mutapi

2011-05-01

Full Text Available In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2-86 years naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5-16 years were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

DEFF Research Database (Denmark)

Pörksen, Sven; Laborie, Lene Bjerke; Nielsen, Lotte

2010-01-01

BACKGROUND: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA......-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. MATERIALS AND METHODS: In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months...... of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea...

Incidence and progression rates of age-related maculopathy: the Rotterdam Study

NARCIS (Netherlands)

J.J.M. Willemse-Assink (Jacqueline); R. van Leeuwen (Redmer); R.C.W. Wolfs (Roger); J.R. Vingerling (Hans); Th. Stijnen (Theo); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); A. Hofman (Albert)

2001-01-01

textabstractPURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects

[Study of anti-idiotype antibodies to human monoclonal antibody].

Science.gov (United States)

Harada, R; Takahashi, N; Owaki, I; Kannagi, R; Endo, N; Morita, N; Inoue, M

1992-02-01

A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda.

Science.gov (United States)

Ssewanyana, Isaac; Arinaitwe, Emmanuel; Nankabirwa, Joaniter I; Yeka, Adoke; Sullivan, Richard; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Mayanja-Kizza, Harriet; Drakeley, Chris; Greenhouse, Bryan; Tetteh, Kevin K A

2017-02-10

People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as

Studies of nontarget-mediated distribution of human full-length IgG1 antibody and its FAb fragment in cardiovascular and metabolic-related tissues.

Science.gov (United States)

Davidsson, Pia; Söderling, Ann-Sofi; Svensson, Lena; Ahnmark, Andrea; Flodin, Christine; Wanag, Ewa; Screpanti-Sundqvist, Valentina; Gennemark, Peter

2015-05-01

Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10 mg/kg of either human IgG1or its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax ) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection

DEFF Research Database (Denmark)

Pedersen, C; Nielsen, C M; Vestergaard, B F

1987-01-01

and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test......A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte...... count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients...

Organizing, exploring, and analyzing antibody sequence data: the case for relational-database managers.

Science.gov (United States)

Owens, John

2009-01-01

Technological advances in the acquisition of DNA and protein sequence information and the resulting onrush of data can quickly overwhelm the scientist unprepared for the volume of information that must be evaluated and carefully dissected to discover its significance. Few laboratories have the luxury of dedicated personnel to organize, analyze, or consistently record a mix of arriving sequence data. A methodology based on a modern relational-database manager is presented that is both a natural storage vessel for antibody sequence information and a conduit for organizing and exploring sequence data and accompanying annotation text. The expertise necessary to implement such a plan is equal to that required by electronic word processors or spreadsheet applications. Antibody sequence projects maintained as independent databases are selectively unified by the relational-database manager into larger database families that contribute to local analyses, reports, interactive HTML pages, or exported to facilities dedicated to sophisticated sequence analysis techniques. Database files are transposable among current versions of Microsoft, Macintosh, and UNIX operating systems.

Relation between enzyme-linked immunosorbent assay and radioimmunoassay for detection of antibodies to the capsular polysaccharide of Haemophilus influenzae type b

International Nuclear Information System (INIS)

Kristensen, K.; Weis Bentzon, M.

1992-01-01

The measurement of antibodies to the capsular polysaccharide (PRP) of Haemophilus influenzae type b (Hib) is important because vaccines inducing such antibodies are now available. We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) for detection of these antibodies based on direct coating of the plates with tyraminated PRP. The assay fulfilled the requirements for parallel line assays; it was sensitive, specific, and reproducible with a coefficient of variation between days of 19%. Results from the ELISA were compared with results from radioimmunoassay and a correlation coefficient of 0.93 was found. Results obtained by the two methods were proportional and the relation was indepenedent of the antibody level. The relation between them was also unaffected by the contribution of different antibody isotypes, indicating that these were measured to the same extent by both methods. ELISA employing direct coating of the plates with tyraminated PRP represents a useful alternative for detection of antibodies when studying immunogenicity of Hib vaccines. (au)

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2...

IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

DEFF Research Database (Denmark)

Ross, Christian; Engler, Claus Bødker; Sander, Birgit

2002-01-01

We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

Antibody-radioisotope conjugates for tumor localization and treatment

International Nuclear Information System (INIS)

Larson, S.M.; Carrasquillo, J.A.

1985-01-01

In principle, anti-tumor antibodies can be used to carry radioactivity to tumors for in-vivo diagnosis and treatment of cancer. First, for diagnostic purposes, an antibody that targets a specific antigen (for example, the p97 antigen of human melanoma tumor), is labeled with a tracer amount of radioactivity. When this antibody-radioisotope conjugate is injected into the blood stream, the antibody carries the radioactivity throughout the body and in time, percolates through all the tissues of the body. Because the tumor has specific antigens to which the antibody can bind, the antibody conjugate progressively accumulates in the tumor. Using conventional nuclear medicine imaging equipment, the body of the patient is scanned for radioactivity content, and a map of the distribution of the radioactivity is displayed on photographic film. The tumor shows up as a dense area of radio-activity. These same antibody-radioisotope conjugates may be used for therapy of tumors, except that in this case large amounts of radioactivity are loaded on the antibody. After localization of the conjugate there is sufficient radiation deposited in the tumor of radiotherapy. The success of this approach in the clinic is determined in large measure by the concentration gradient that can be achieved between tissue antibody conjugate in tumor versus normal tissue

Discovery Of Human Antibodies Against Spitting Cobra Toxins

DEFF Research Database (Denmark)

Bojsen-Møller, Laura; Lohse, Brian; Harrison, Robert

Current snakebite envenoming treatment options consist of animal-derived antisera and are associated with severe adverse reactions due to the heterologous nature of the animal-derived antibodies present in these antisera, and the presence of therapeutically irrelevant antibodies. The African...... spitting cobras are among the most medically important snakes in sub-Saharan regions due to the severity of the clinical outcomes caused by their cytotoxic venom, which is derived from cytotoxins of the 3FTx toxin family and PLA2. Here we report the results of our progress in identifying human antibodies...... targeting relevant toxins from the venom of the black necked spitting cobra (Naja nigricolis)....

Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics.

Science.gov (United States)

Zhou, Lei; Hoofring, Sarah A; Wu, Yu; Vu, Thuy; Ma, Peiming; Swanson, Steven J; Chirmule, Narendra; Starcevic, Marta

2013-01-01

The availability of highly sensitive immunoassays enables the detection of antidrug antibody (ADA) responses of various concentrations and affinities. The analysis of the impact of antibody status on drug pharmacokinetics (PK) is confounded by the presence of low-affinity or low-concentration antibody responses within the dataset. In a phase 2 clinical trial, a large proportion of subjects (45%) developed ADA following weekly dosing with AMG 317, a fully human monoclonal antibody therapeutic. The antibody responses displayed a wide range of relative concentrations (30 ng/mL to >13 μg/mL) and peaked at various times during the study. To evaluate the impact of immunogenicity on PK, AMG 317 concentration data were analyzed following stratification by dose group, time point, antibody status (positive or negative), and antibody level (relative concentration). With dose group as a stratifying variable, a moderate reduction in AMG 317 levels (AMG 317 levels was revealed when antibody data was stratified by both time point and antibody level. In general, high ADA concentrations (>500 ng/mL) and later time points (week 12) were associated with significantly (up to 97%) lower trough AMG 317 concentrations. The use of quasi-quantitative antibody data and appropriate statistical methods was critical for the most comprehensive evaluation of the impact of immunogenicity on PK.

Radioimmunological proof of thyroglobulin antibodies in humans by the use of a double antibody method

International Nuclear Information System (INIS)

Waller, V.

1982-01-01

Thyroid antibodies, especially thyroglobulin antibodies, allow themselves to be proven with the double antibody method, in competitive radio binding assays and with the solid phase technique. These methods offer advantages relative to sensitivity and quantifiability. In this work a sensitive radioimmunoassay as a double antibody method was worked out whereby a 125 I-thyroglobulin/thyroglobulin antibody immune complex was precipitated out using anti-human immunoglobulin. The measured results from the radioimmunoassay show a good correlation with the results of the immune histological findings. A high to very high Tg antibody level occurs with autoimmune thyroiditis (80%), primary hypothyroidism (74%) and hyperthyroidism (70%). The control values with healthy people came to less than 5% specific binding. In correlation with the results of other authors this method is advantageous relative to test start and evaluation procedures. (orig.) [de

Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model.

Directory of Open Access Journals (Sweden)

Natalia Makarova

2011-04-01

Full Text Available Xenotropic murine leukemia virus-related virus (XMRV was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC. Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP that had the size and morphology of live infectious XMRV.Immunization elicited Env-specific binding and neutralizing antibodies (NAb against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.

Identification of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein A2

DEFF Research Database (Denmark)

Tronstrøm, Julie; Dragborg, Anette H.; Hansen, Paul Robert

2014-01-01

to as RA33. In the absence of citrulline antibodies, RA33 antibodies have been suggested to be associated with a milder disease course. In this study we screened the reactivity of a monoclonal antibody to RA33-derived peptides by modified enzyme-linked immunosorbent assays (ELISA). Terminally truncated......Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by progressive joint destruction and disability. Classical autoantibodies of RA are rheumatoid factors and citrulline antibodies. Patients positive for these autoantibodies are usually associated with a progressive disease...... course. A subgroup of RA patients does not express citrulline antibodies, instead are approximately 35% of these anti-citrulline-negative patients reported to express autoantibodies to the heterogeneous nucleoriboprotein A2, a ribonucleoprotein involved in RNA transport and processing also referred...

Effects of genetic engineering on the pharmacokinetics of antibodies

International Nuclear Information System (INIS)

Colcher, D.; Goel, A.; Pavlinkova, G.; Beresford, G.; Booth, B.; Batra, S.K.

1999-01-01

Monoclonal antibodies (MAbs) may be considered 'magic bullets' due to their ability to recognize and eradicate malignant cells. MAbs, however, have practical limitations for their rapid application in the clinics. The structure of the antibody molecules can be engineered to modify functional domains such as antigen-binding sites and/or effectors functions. Advanced in genetic engineering have provided rapid progress the development of new immunoglobulin constructs of MAbs with defined research and therapeutic application. Recombinant antibody constructs are being engineered, such as human mouse chimeric, domain-dispositioned, domain-deleted, humanized and single-chain Fv fragments. Genetically-engineered antibodies differ in size and rate of catabolism. Pharmacokinetics studies show that the intact IgG (150 kD), enzymatically derived fragments Fab' (50 kD) and single chain Fv (28 kD) have different clearance rates. These antibody forms clear 50% from the blood pool in 2.1 days, 30 minutes and 10 minutes, respectively. Genetically-engineered antibodies make a new class of immunotherapeutic tracers for cancer treatment

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

Science.gov (United States)

Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

2012-10-01

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

Quality assurance after process changes of the production of a therapeutic antibody.

Science.gov (United States)

Brass, J M; Krummen, K; Moll-Kaufmann, C

1996-12-01

Process development for the production of a therapeutic humanised antibody is a very complex operation. It involves recombinant genetics, verification of a strong expression system, gene amplification, characterisation of a stable host cell expression system, optimisation and design of the mammalian cell culture fermentation system and development of an efficient recovery process resulting in high yields and product quality. Rapid progress in the field and the wish of some pharmaceutical companies for outsourcing their production are the driving forces for process changes relatively late in the development phase. This literature survey is aimed at identifying the limits of acceptable process changes in up scaling of the fermentation and down stream processing of biopharmaceuticals and defining the demand in production validation to prove product equivalency and identity of the isolated, purified therapeutic antibody.

Targeting Malignant Brain Tumors with Antibodies

Directory of Open Access Journals (Sweden)

Rok Razpotnik

2017-09-01

-based therapy using the antibody to bind to the specific target(s. Finally, the current clinical trials are reviewed, showing the most recent progress of attractive approaches to deliver therapeutic antibodies across the BBB aiming at the specific antigen.

Radiolabeled antibodies in cancer. Oncology Overview

International Nuclear Information System (INIS)

1984-11-01

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories through the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiolabeled antibodies--labeling and imaging techniques; Radiolabeled antibodies--carcinoembryonic antigen; Radiolabeled antibodies--alpha-fetoprotein; Radiolabeled antibodies--human chorionic gonadotropin; Radiolabeled antibodies--ferritin; Radiolabeled antibodies--imaging of colorectal tumors; Radiolabeled antibodies--imaging of malignant melanoma; Radiolabeled antibodies--imaging of urogenital tumors; Radiolabeled antibodies--imaging of thyroid tumors; Radiolabeled antibodies--other clinical studies; Radiolabeled antibodies--selected preclinical studies; Radiolabeled antibodies--reviews

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

Science.gov (United States)

Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

1996-06-01

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

Science.gov (United States)

Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

2001-09-15

Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.

Tumor localization of 131I-labeled antibodies by radionuclide imaging

International Nuclear Information System (INIS)

Ghose, T.; Tai, J.; Aquino, J.; Guclu, A.; Norvell, S.; MacDondald, A.

1975-01-01

Intravenous injections of 131 I-labeled anti-EL4 lymphoma antibodies showed progressive localization of radioactivity in EL4 transplants but not in B16 melanoma in mice carrying both tumors. Normal rabbit globulin labeled with 131 I did not localize in either tumor and cleared more slowly from the internal organs. Metastatic localization of intravenous 131 I-labeled anti-tumor antibodies was also observed in two cancer patients. (U.S.)

High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.

Science.gov (United States)

Okayama, A; Chen, Y M; Tachibana, N; Shioiri, S; Lee, T H; Tsuda, K; Essex, M

1991-01-01

Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

Opalescence of an IgG2 monoclonal antibody solution as it relates to liquid-liquid phase separation.

Science.gov (United States)

Mason, Bruce D; Zhang, Le; Remmele, Richard L; Zhang, Jifeng

2011-11-01

Opalescence for a monoclonal antibody solution was systematically studied with respect to temperature, protein concentration, ionic strength (using KCl), and pH conditions. Multiple techniques, including measurement of light scattering at 90° and transmission, Tyndall test, and microscopy, were deployed to examine the opalescence behavior. Near the vicinity of the critical point on the liquid-liquid coexistence curve in the temperature-protein concentration phase diagram, the enhanced concentration fluctuations significantly contributed to the critical opalescence evidently by formation of small liquid droplets. Furthermore, our data confirm that away from the critical point, the opalescence behavior is related to the antibody self-association (agglomeration) caused by the attractive antibody-antibody interactions. As expected, at a pH near the pI of the antibody, the solution became less opalescent as the ionic strength increased. However, at a pH below the pI, the opalescence of the solution became stronger, reached a maximum, and then began to drop as the ionic strength further increased. The change in the opalescence correlated well with the trends of protein-protein interactions revealed by the critical temperature from the liquid-liquid phase separation. Copyright © 2011 Wiley-Liss, Inc.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

Science.gov (United States)

Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Food related antibodies in headache patients.

OpenAIRE

Merrett, J; Peatfield, R C; Rose, F C; Merrett, T G

1983-01-01

Highly sensitive and specific methods for assaying IgE and IgG4 for antibodies in serum have been developed in order to test a recent suggestion that food allergy is a major cause of migraine. Sera were collected from 208 adults--74 with dietary migraine, 45 with non-dietary migraine, 29 with cluster headache and 60 controls. No significant differences were identified between any of the groups with the one exception that cluster headache patients had significantly raised levels of total serum...

Natural antibodies related to metabolic and mammary health in dairy cows

NARCIS (Netherlands)

Knegsel, van A.T.M.; Hostens, M.; Vries Reilingh, de G.; Lammers, A.; Kemp, B.; Opsomer, G.; Parmentier, H.K.

2012-01-01

Natural antibodies (NAb) are defined as antibodies that circulate in normal healthy individuals under the absence of deliberate antigenic stimulation. Two types of NAb are distinguished: NAb towards exogenous antigens and NAb towards autoantigens (N(A)Ab). The objectives of the current study were

Clarification technologies for monoclonal antibody manufacturing processes: Current state and future perspectives.

Science.gov (United States)

Singh, Nripen; Arunkumar, Abhiram; Chollangi, Srinivas; Tan, Zhijun George; Borys, Michael; Li, Zheng Jian

2016-04-01

Considerable progress has been made increasing productivity of cell cultures to meet the rapidly growing demand for antibody biopharmaceuticals through increased cell densities and longer culture times. This in turn has dramatically increased the burden of process and product related impurities on the purification processes. In addition, current trends in the biopharmaceutical industry point toward both increased productivity and targeting smaller patient populations for new indications. Taken together, these developments are driving the industry to explore alternative separation technologies as a future manufacturing strategy. Clarification technologies well established in other industries, such as flocculation and precipitation are increasingly considered as a viable solution to address this bottleneck in antibody processes. However, several technical issues need to be fully addressed including suitability as a platform application, robustness, process cost, toxicity, and clearance. This review will focus on recent efforts to incorporate new generation clarification technologies for mammalian cell cultures producing monoclonal antibodies as well as challenges to their implementation supported by a case study. © 2015 Wiley Periodicals, Inc.

Severe antiphospholipid antibody syndrome - response to plasmapheresis and rituximab.

Science.gov (United States)

Gkogkolou, Paraskevi; Ehrchen, Jan; Goerge, Tobias

2017-09-01

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, recurrent abortions and detection of antiphospholipid antibodies. In fulminant cases, involvement of multiple organs can lead to significant morbidity and even fatal outcomes, so that a rapid, interdisciplinary treatment is needed. Here, we describe the case of a 39-year-old woman with a severe hard-to-treat APS with arterial occlusion and progressive skin necrosis, who was successfully treated with a combination therapy with plasmapheresis and rituximab. The treatment led to complete remission of the skin lesions for over a year. Clinical response correlated with a long-lasting reduction of antiphospholipid antibodies and B-cell depletion. This case demonstrates the use of antiphospholipid antibodies for monitoring APS-activity and shows that this severe vascular disease requires rigorous therapeutic approaches.

Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression.

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Oudin, Madeleine J; Hughes, Shannon K; Rohani, Nazanin; Moufarrej, Mira N; Jones, Joan G; Condeelis, John S; Lauffenburger, Douglas A; Gertler, Frank B

2016-03-01

Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena(INV) isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena(INV) within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena(INV) isoform-specific monoclonal antibody and used it to examine Mena(INV) expression patterns in mouse mammary and human breast tumors. Mena(INV) expression increases during tumor progression and to examine the relationship between Mena(INV) expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena(INV) robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena(INV)-isoform specific antibody, and provide the first description of endogenous Mena(INV) protein expression in mouse and human tumors.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

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Lang Yi

2016-01-01

Full Text Available The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA patients, and healthy controls (HC in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28. In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

In situ click chemistry: from small molecule discovery to synthetic antibodies

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Agnew, Heather D.; Lai, Bert; Lee, Su Seong; Lim, Jaehong; Nag, Arundhati; Pitram, Suresh; Rohde, Rosemary; Heath, James R.

2013-01-01

Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents. PMID:22836343

Progressive cerebral atrophy in neuromyelitis optica.

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Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

2015-12-01

We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

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Fanale, Michelle A; Younes, Anas

2007-01-01

resistant to a targeted therapy by activating an alternative pathway to evade apoptosis has driven studies that combine antibodies such as epratuzumab plus rituximab (ER) or ER plus chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) [ER-CHOP], inotuzumab ozogamicin plus rituximab, alemtuzumab plus CHOP (CHOP-C), bevacizumab plus rituximab, and now the combination of rApo2L/TRAIL plus rituximab. As a result of the expansion of research in this area, several treatment-specific adverse effects have been noted, including infusion-related reactions for rituximab, myelosuppression secondary to (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, and immunosuppression leading to infectious complications for alemtuzumab. Also, soluble forms of the antigens (sCD30) are now being investigated as potential mechanisms of resistance to antibody treatments by binding the antibody before the drug can bind to the lymphoma cell. In addition, it has also become apparent that these antibodies often have a dose-dependent half-life (rituximab) or long half-lives of up to 2-3 weeks (epratuzumab and galiximab) with a consequent delay to a response, thus influencing how long we should wait for a response before declaring an antibody to be ineffective. Antibody-based therapeutic approaches have already had a profound impact on the treatment of NHL, and it is almost certain that, as their clinical development progresses, we will continue to refine the optimum methods of incorporating these drugs in NHL treatment in order to offer our patients the best clinical benefits.

Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort

DEFF Research Database (Denmark)

Olsson, Tomas; Achiron, Anat; Alfredsson, Lars

2013-01-01

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody...... prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49...

Identification of antibody glycosylation structures that predict monoclonal antibody Fc-effector function.

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Chung, Amy W; Crispin, Max; Pritchard, Laura; Robinson, Hannah; Gorny, Miroslaw K; Yu, Xiaojie; Bailey-Kellogg, Chris; Ackerman, Margaret E; Scanlan, Chris; Zolla-Pazner, Susan; Alter, Galit

2014-11-13

To determine monoclonal antibody (mAb) features that predict fragment crystalizable (Fc)-mediated effector functions against HIV. Monoclonal antibodies, derived from Chinese hamster ovary cells or Epstein-Barr virus-immortalized mouse heteromyelomas, with specificity to key regions of the HIV envelope including gp120-V2, gp120-V3 loop, gp120-CD4(+) binding site, and gp41-specific antibodies, were functionally profiled to determine the relative contribution of the variable and constant domain features of the antibodies in driving robust Fc-effector functions. Each mAb was assayed for antibody-binding affinity to gp140(SR162), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and for the ability to bind to FcγRIIa, FcγRIIb and FcγRIIIa receptors. Antibody glycan profiles were determined by HPLC. Neither the specificity nor the affinity of the mAbs determined the potency of Fc-effector function. FcγRIIIa binding strongly predicted ADCC and decreased galactose content inversely correlated with ADCP, whereas N-glycolylneuraminic acid-containing structures exhibited enhanced ADCP. Additionally, the bi-antenary glycan arm onto which galactose was added predicted enhanced binding to FcγRIIIa and ADCC activity, independent of the specificity of the mAb. Our studies point to the specific Fc-glycan structures that can selectively promote Fc-effector functions independently of the antibody specificity. Furthermore, we demonstrated antibody glycan structures associated with enhanced ADCP activity, an emerging Fc-effector function that may aid in the control and clearance of HIV infection.

Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy

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Hao Chen

2017-08-01

Full Text Available Antibody-drug conjugates (ADCs are a class of highly potent biopharmaceutical drugs generated by conjugating cytotoxic drugs with specific monoclonal antibodies through appropriate linkers. Specific antibodies used to guide potent warheads to tumor tissues can effectively reduce undesired side effects of the cytotoxic drugs. An in-depth understanding of antibodies, linkers, conjugation strategies, cytotoxic drugs, and their molecular targets has led to the successful development of several approved ADCs. These ADCs are powerful therapeutics for cancer treatment, enabling wider therapeutic windows, improved pharmacokinetic/pharmacodynamic properties, and enhanced efficacy. Since tubulin inhibitors are one of the most successful cytotoxic drugs in the ADC armamentarium, this review focuses on the progress in tubulin inhibitor-based ADCs, as well as lessons learned from the unsuccessful ADCs containing tubulin inhibitors. This review should be helpful to facilitate future development of new generations of tubulin inhibitor-based ADCs for cancer therapy.

Digital gangrene associated with anticentromere antibodies: a case report

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Nair Bindu

2010-06-01

Full Text Available Abstract Introduction Anticentromere antibodies have been associated with peripheral vascular occlusive disease, most frequently accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene with no other clinical associations except positive anticentromere antibodies. Case presentation Our patient, a 53-year-old Caucasian woman, non-smoker, presented with progressive pain and blackening of the distal right third finger over the preceding five weeks. No sclerodactyly was evident. She was anticentromere antibody positive at greater than 100 U/mL. Angiography revealed diffuse distal vasculopathy in both upper extremities. Other investigations were unremarkable. Conclusions It is rare for anticentromere antibody-associated digital necrosis to develop without concomitant sclerodactyly. However, this patient's case illustrates the need to consider an autoimmune contribution to the pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease.

High throughput screening for antibody induced complement-dependent cytotoxicity in early antibody discovery using homogeneous macroconfocal fluorescence imaging

NARCIS (Netherlands)

Gerritsen, Arnout F.; Bosch, Martijn; de Weers, Michel; van de Winkel, Jan G. J.; Parren, Paul W. H. I.

2010-01-01

Complement-dependent cytotoxicity (CDC) represents an important Fc-mediated effector function of antibodies and is a quality often sought in candidates for therapeutic antibody development in cancer. Antibodies inducing potent CDC are relatively rare as the ability to induce CDC is strongly

Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex

NARCIS (Netherlands)

Goudsmit, J.; Wolters, E. C.; Bakker, M.; Smit, L.; van der Noordaa, J.; Hische, E. A.; Tutuarima, J. A.; van der Helm, H. J.

1986-01-01

De novo synthesis in the central nervous system of IgG antibodies to human T cell lymphotropic virus type III (HTLV-III) (lymphadenopathy associated virus) was shown in seven of 10 seropositive men who had syphilis but not the acquired immune deficiency syndrome (AIDS) or AIDS related complex. None

Integration of Antibody Array Technology into Drug Discovery and Development.

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Huang, Wei; Whittaker, Kelly; Zhang, Huihua; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan

Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.

IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

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Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

2015-01-01

Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

Microbial platform technology for recombinant antibody fragment production: A review.

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Gupta, Sanjeev Kumar; Shukla, Pratyoosh

2017-02-01

Recombinant antibody fragments are being used for the last few years as an important therapeutic protein to cure various critical and life threatening human diseases. Several expression platforms now days employed for the production of these recombinant fragments, out of which bacterial system has emerged a promising host for higher expression. Since, a small antibody fragment unlike full antibody does not require human-like post-translational modification therefore it is potentially expressed in prokaryotic production system. Recently, small antibody fragments such as scFvs (single-chain variable fragments) and Fabs (antibody fragments) which does not require glycosylation are successfully produced in bacteria and have commercially launched for therapeutic use as these fragments shows better tissue penetration and less immunogenic to human body compared to full-size antibody. Recently developed Wacker's ESETEC secretion technology is an efficient technology for the expression and secretion of the antibody fragment (Fab) exceeded up to 4.0 g/L while scFv up to 3.5 g/L into the fermentation broth. The Pfenex system and pOP prokaryotic expression vector are another platform used for the considerably good amount of antibody fragment production successfully. In this review, we summarize the recent progress on various expression platforms and cloning approaches for the production of different forms of antibody fragments in E. coli.

Antithyroglobulin antibody

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Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model.

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Liang, Lin; Hur, Jung; Kang, Ji Young; Rhee, Chin Kook; Kim, Young Kyoon; Lee, Sook Young

2018-04-19

The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

A Single Domain–Based Anti-Her2 Antibody Has Potent Antitumor Activities

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Xiaoqiong Wu

2018-04-01

Full Text Available Human epidermal growth factor receptor 2 (HER2 is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

Man-made antibodies and immunoconjugates with desired properties: function optimization using structural engineering

International Nuclear Information System (INIS)

Deyev, S M; Lebedenko, E N; Petrovskaya, L E; Dolgikh, D A; Gabibov, A G; Kirpichnikov, M P

2015-01-01

The review outlines progress and problems in the design of non-natural antibodies for clinical applications over the past 10–15 years. The modular structure of natural antibodies and approaches to its targeted modifications and combination with other structural elements and effector molecules are considered. The review covers modern methods for immunoglobulin engineering and promising strategies for the creation and applications of monoclonal antibodies, their derivatives and analogues, including abzymes and scaffolds, oriented to the use in the diagnosis and targeted therapy of cancer and other socially significant diseases. The bibliography includes 225 references

Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

Science.gov (United States)

Wilkinson, Trevor C I

2016-06-15

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Thrombosis and antiphospholipid antibody syndrome during acute Q fever

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Million, Matthieu; Bardin, Nathalie; Bessis, Simon; Nouiakh, Nadia; Douliery, Charlaine; Edouard, Sophie; Angelakis, Emmanouil; Bosseray, Annick; Epaulard, Olivier; Branger, Stéphanie; Chaudier, Bernard; Blanc-Laserre, Karine; Ferreira-Maldent, Nicole; Demonchy, Elisa; Roblot, France; Reynes, Jacques; Djossou, Felix; Protopopescu, Camelia; Carrieri, Patrizia; Camoin-Jau, Laurence; Mege, Jean-Louis; Raoult, Didier

2017-01-01

Abstract Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever. Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis. Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85–113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73–0.93], P antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine

Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

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Zhuang, Xiaodong; Bicknell, Roy

2016-01-01

A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

Antibodies to dopamine: radioimmunological study of specificity in relation to immunocytochemistry

Energy Technology Data Exchange (ETDEWEB)

Geffard, M.; Kah, O.; Onteniente, B.; Seguela, P.; Le Moal, M.; Delaage, M.

1984-06-01

Two classes of anti-3,4- dihydroxyphenylethylamine (dopamine) antibodies were raised in rabbits using dopamine conjugated to albumin either via formaldehyde or via glutaraldehyde. Each was usable for immunohistochemical detection of dopamine neurons provided that the tissue was fixed by the homologous cross-linking agent. However, anti-dopamine-glutaraldehyde antibodies turned out to be of more general use because of the better fixative properties of glutaraldehyde which fixed dopamine in rat and in teleost, whereas formaldehyde only worked in lower vertebrates (such as goldfish) and not in rat brain. The specificity of anti-dopamine-glutaraldehyde antibodies was firmly established by competition experiments in equilibrium dialysis, using an immunoreactive tritiated derivative synthesized by coupling dopamine to N-alpha-acetyl-L-lysine N-methylamide via glutaraldehyde. Specificity studies in vitro and immunohistological results demonstrating the specific staining of dopaminergic neurons were found to correlate well.

Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

International Nuclear Information System (INIS)

Nagai, Kentaro; Nakahata, Shingo; Shimosaki, Shunsuke; Tamura, Tomohiro; Kondo, Yuudai; Baba, Takashi; Taki, Tomohiko; Taniwaki, Masafumi; Kurosawa, Gene; Sudo, Yukio; Okada, Seiji; Sakoda, Sumio; Morishita, Kazuhiro

2014-01-01

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC

Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

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Igawa, Tomoyuki

2017-01-01

Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.

Radioimmunoassay with heterologous antibody (hetero-antibody RIA)

International Nuclear Information System (INIS)

Iwasawa, Atsushi; Hayashi, Hiroaki; Itoh, Zen; Wakabayashi, Katsumi

1991-01-01

To develop a homologous radioimmunoassay (RIA) for a hormone of a small or rare animal often meets difficulty in collecting a large amount of purified antigen required for antibody production. On the other hand, to employ a heterologous RIA to estimate the hormone often gives poor sensitivity. To overcome this difficulty, a 'hetero-antibody' RIA was studied. In a hetero-antibody RIA system, a purified preparation of a hormone is used for radioiodination and standardization and a heterologous antibody to the hormone is used for the first antibody. Canine motilin and rat LH were selected as examples, and anti-porcine motilin and anti-hCG, anti-hCGβ or anti-ovine LHβ was used as the heterologous antibody. The sensitivities of the hetero-antibody RIAs were much higher than those of heterologous RIAs in any case, showing that these hetero-antibody RIA systems were suitable for practical use. To clarify the principle of hetero-antibody RIA, antiserum to porcine motilin was fractionated on an affinity column where canine motilin was immobilized. The fraction bound had greater constants of affinity with both porcine and canine motilins than the rest of the antibody fractions. This fraction also reacted with a synthetic peptide corresponding to the C-terminal sequence common to porcine and canine motilins in a competitive binding test with labeled canine motilin. These results suggest that an antibody population having high affinity and cross-reactivity is present in polyclonal antiserum and indicate that the population can be used in hetero-antibody RIA at an appropriate concentration. (author)

Identification of a Monoclonal Antibody That Attenuates Antiphospholipid Syndrome-Related Pregnancy Complications and Thrombosis

Science.gov (United States)

Mineo, Chieko; Lanier, Lane; Jung, Eunjeong; Sengupta, Samarpita; Ulrich, Victoria; Sacharidou, Anastasia; Tarango, Cristina; Osunbunmi, Olutoye; Shen, Yu-Min; Salmon, Jane E.; Brekken, Rolf A.; Huang, Xianming; Shaul, Philip W.

2016-01-01

In the antiphospholipid syndrome (APS), patients produce antiphospholipid antibodies (aPL) that promote thrombosis and adverse pregnancy outcomes. Current therapy with anticoagulation is only partially effective and associated with multiple complications. We previously discovered that aPL recognition of cell surface β2-glycoprotein I (β2-GPI) initiates apolipoprotein E receptor 2 (apoER2)-dependent signaling in endothelial cells and in placental trophoblasts that ultimately promotes thrombosis and fetal loss, respectively. Here we sought to identify a monoclonal antibody (mAb) to β2-GPI that negates aPL-induced processes in cell culture and APS disease endpoints in mice. In a screen measuring endothelial NO synthase (eNOS) activity in cultured endothelial cells, we found that whereas aPL inhibit eNOS, the mAb 1N11 does not, and instead 1N11 prevents aPL action. Coimmunoprecipitation studies revealed that 1N11 decreases pathogenic antibody binding to β2-GPI, and it blocks aPL-induced complex formation between β2-GPI and apoER2. 1N11 also prevents aPL antagonism of endothelial cell migration, and in mice it reverses the impairment in reendothelialization caused by aPL, which underlies the non-thrombotic vascular occlusion provoked by disease-causing antibodies. In addition, aPL inhibition of trophoblast proliferation and migration is negated by 1N11, and the more than 6-fold increase in fetal resorption caused by aPL in pregnant mice is prevented by 1N11. Furthermore, the promotion of thrombosis by aPL is negated by 1N11. Thus, 1N11 has been identified as an mAb that attenuates APS-related pregnancy complications and thrombosis in mice. 1N11 may provide an efficacious, mechanism-based therapy to combat the often devastating conditions suffered by APS patients. PMID:27463336

Modification of Antibody Function by Mutagenesis.

Science.gov (United States)

Dasch, James R; Dasch, Amy L

2017-09-01

The ability to "fine-tune" recombinant antibodies by mutagenesis separates recombinant antibodies from hybridoma-derived antibodies because the latter are locked with respect to their properties. Recombinant antibodies can be modified to suit the application: Changes in isotype, format (e.g., scFv, Fab, bispecific antibodies), and specificity can be made once the heavy- and light-chain sequences are available. After immunoglobulin heavy and light chains for a particular antibody have been cloned, the binding site-namely, the complementarity determining regions (CDR)-can be manipulated by mutagenesis to obtain antibody variants with improved properties. The method described here is relatively simple, uses commercially available reagents, and is effective. Using the pComb3H vector, a commercial mutagenesis kit, PfuTurbo polymerase (Agilent), and two mutagenic primers, a library of phage with mutagenized heavy and light CDR3 can be obtained. © 2017 Cold Spring Harbor Laboratory Press.

B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination.

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Kavitha Kothur

Full Text Available Myelin oligodendrocyte glycoprotein antibody (MOG Ab associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination.To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS and -negative (NEG groups.We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis (ADEM = 8, transverse myelitis (TM = 2 n = 10] and serum MOG Ab NEG (ADEM = 5, TM = 4, n = 9 demyelination. We generated normative data using CSF from 20 non-inflammatory neurological controls.The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL, BAFF and CCL19 as well as some of Th17 related cytokines (IL-6 AND G-CSF compared to MOG Ab NEG group (all p<0.01. In addition, patients with elevated CSF MOG antibodies had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF MOG antibodies.Our findings suggest that MOG Ab POS patients have a more pronounced CNS inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/chemokine profiling provides new insight into disease pathogenesis, and improves our ability to monitor inflammation and response to treatment. In addition, some of these molecules may represent potential immunomodulatory targets.

Antibodies and Selection of Monoclonal Antibodies.

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Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology.

Whole-body effective half-lives for radiolabeled antibodies and related issues

International Nuclear Information System (INIS)

Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

1996-08-01

Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations

Whole-body effective half-lives for radiolabeled antibodies and related issues

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Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

1996-08-01

Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations.

Complement-fixing antibodies against denatured HLA and MICA antigens are associated with antibody mediated rejection.

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Cai, Junchao; Terasaki, Paul I; Zhu, Dong; Lachmann, Nils; Schönemann, Constanze; Everly, Matthew J; Qing, Xin

2016-02-01

We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q. In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q. Thirty percent of patients had antibodies against denatured HLA class I, II, or MICA antigens. Among them, 8.5% and 21.5% of all patients had c1q-fixing and non c1q-fixing antibodies respectively. There was no significant difference on graft survival between patients with or without antibodies against denatured HLA/MICA. However, when these antibodies were further classified according to their ability to fix c1q, patients with c1q-fixing antibodies had a significantly lower graft survival rate than patients without antibodies or patients with non c1q-fixing antibodies (p=0.008). In 169 patients who lost renal grafts, 44% of them had c1q-fixing antibodies against denatured HLA/MICA antigens, which was significantly higher than that in patients with functioning renal transplants (25%, pantibodies were more significantly associated with graft failure caused by AMR (72.73%) or mixed AMR/CMR (61.9%) as compared to failure due to CMR (35.3%) or other causes (39.2%) (p=0.026). Transplant recipients had antibodies against denatured HLA class I, II, and MICA antigens. However, only c1q-fixing antibodies were associated with graft failure which was related to antibody mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course.

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Haran, John Patrick; Hoaglin, David C; Chen, Huaiqing; Boyer, Edward W; Lu, Shan

2014-08-01

Early antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated. Using hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers. There were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008-2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays. Acutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, pinfection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (pacute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores. Copyright © 2014 Elsevier B.V. All rights reserved.

Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

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Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

2017-12-06

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these

[A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

Science.gov (United States)

Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

2017-01-01

  A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis.

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Ashraf, S Q; Umana, P; Mössner, E; Ntouroupi, T; Brünker, P; Schmidt, C; Wilding, J L; Mortensen, N J; Bodmer, W F

2009-11-17

The effect of glycoengineering a membrane specific anti-carcinoembryonic antigen (CEA) (this paper uses the original term CEA for the formally designated CEACAM5) antibody (PR1A3) on its ability to enhance killing of colorectal cancer (CRC) cell lines by human immune effector cells was assessed. In vivo efficacy of the antibody was also tested. The antibody was modified using EBNA cells cotransfected with beta-1,4-N-acetylglucosaminyltransferase III and the humanised hPR1A3 antibody genes. The resulting alteration of the Fc segment glycosylation pattern enhances the antibody's binding affinity to the FcgammaRIIIa receptor on human immune effector cells but does not alter the antibody's binding capacity. Antibody-dependent cellular cytotoxicity (ADCC) is inhibited in the presence of anti-FcgammaRIII blocking antibodies. This glycovariant of hPR1A3 enhances ADCC 10-fold relative to the parent unmodified antibody using either unfractionated peripheral blood mononuclear or natural killer (NK) cells and CEA-positive CRC cells as targets. NK cells are far more potent in eliciting ADCC than either freshly isolated monocytes or granulocytes. Flow cytometry and automated fluorescent microscopy have been used to show that both versions of hPR1A3 can induce antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages. However, the glycovariant antibody did not mediate enhanced ADCP. This may be explained by the relatively low expression of FcgammaRIIIa on cultured macrophages. In vivo studies show the efficacy of glycoengineered humanised IgG1 PR1A3 in significantly improving survival in a CRC metastatic murine model. The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.

Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.

Science.gov (United States)

Zagury, J F; Sill, A; Blattner, W; Lachgar, A; Le Buanec, H; Richardson, M; Rappaport, J; Hendel, H; Bizzini, B; Gringeri, A; Carcagno, M; Criscuolo, M; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep.

Science.gov (United States)

Herrmann-Hoesing, Lynn M; Noh, Susan M; White, Stephen N; Snekvik, Kevin R; Truscott, Thomas; Knowles, Donald P

2009-04-01

Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.

STREPTOKINASE EFFICACY IN MYOCARDIAL INFARCTION MANAGEMENT: IS IT RELATED TO SERUM ANTISTREPTOKINASE ANTIBODY TITER

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H SHEMIRANI

2000-06-01

Full Text Available Introduction. Antistreptokinase antibodies in sera of individuals with previous streptococcal infection might theoretically influence the thrombolytic activity of streptokinase. Streptokinase as the only thrombolytic drug is used in MI management in Iran. Since, the prevalence of streptococcal infections are higher in Iranian population, it seems that high level of antibodies in sera of patients would decrease the thrombolytic effect of Streptokinase. Methods. Antistreptokinase antibodies were measured by Home Made EL/SA method before streptokinase administration in 126 patients with MI who were admitted to Noor hospital (affiliated to Isfahan University of Medical Sciences and Health Services. The effect of drug with regard to ECG changes in following days were studied and compared. Results. In seventy patients of 126 (13.5 percent, the drug was ineffective and the antibody level was high. While in 25 patients with effective response to drug (no appearing of Q wave, 3 patients have a high level of antibody against streptokinase. Discussion. It seems that high level of serum antistreptokinase antibody titer has no significant interaction with thrombolytic activity of streptokinase in management of MI. However, most accurate study is required to test this hypothesis.

Antinuclear antibodies as ancillary markers in primary biliary cirrhosis.

Science.gov (United States)

Granito, Alessandro; Muratori, Paolo; Quarneti, Chiara; Pappas, Georgios; Cicola, Ronny; Muratori, Luigi

2012-01-01

Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.

Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

Science.gov (United States)

Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

2017-11-10

Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

International Nuclear Information System (INIS)

Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook

1979-01-01

The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

Protective roles of natural IgM antibodies

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Caroline eGrönwall

2012-04-01

Full Text Available Antibodies are a vital part of the armentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens for the enhancement of primitive innate functions. The repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is essential to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythemtosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

Interplay between Natural Killer Cells and Anti-HER2 Antibodies: Perspectives for Breast Cancer Immunotherapy

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Aura Muntasell

2017-11-01

Full Text Available Overexpression of the human epidermal growth factor receptor 2 (HER2 defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models. Antibody-dependent NK cell activation results in the release of cytotoxic granules as well as the secretion of pro-inflammatory cytokines (i.e., IFNγ and TNFα and chemokines. Hence, NK cell tumor suppressive functions include direct cytolytic killing of tumor cells as well as the regulation of subsequent antitumor adaptive immunity. Albeit tumors with gene expression signatures associated to the presence of cytotoxic lymphocyte infiltrates benefit from trastuzumab-based treatment, NK cell-related biomarkers of response/resistance to HER2-specific therapeutic antibodies in breast cancer patients remain elusive. Several variables, including (i the configuration of the patient NK cell repertoire; (ii tumor molecular features (i.e., estrogen receptor expression; (iii concomitant therapeutic regimens (i.e., chemotherapeutic agents, tyrosine kinase inhibitors; and (iv evasion mechanisms developed by progressive breast tumors, have been shown to quantitatively and qualitatively influence antibody-triggered NK cell responses. In this review, we discuss possible interventions for restoring/enhancing the therapeutic activity of HER2 therapeutic antibodies by harnessing NK cell antitumor potential through

Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody

International Nuclear Information System (INIS)

Karube, Yoshiharu; Katsuno, Kentaro; Ito, Sanae; Matsunaga, Kazuhisa; Takata, Jiro; Kuroki, Masahide; Murakami, Masaaki; Matsuoka, Yuji

1999-01-01

The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value. (author)

Improvements in or relating to antibodies active against human hemoglobin Asub(1C)

International Nuclear Information System (INIS)

Javid, J.; Cerami, A.; Koenig, R.J.; Pettis, P.K.

1980-01-01

A method is described for preparing an antibody against human hemoglobin Asub(1c) which is substantially free of cross-reactivity against the human hemoglobins A 0 , Asub(1a) and Asub(1b). The antibodies are collected from cats, goats or sheep following injections of purified hemoglobin Asub(1c) antigen since these animals do not naturally produce hemoglobin Asub(1c). A radioimmunoassay method is also described whereby these antibodies are used to determine the quantity of hemoglobin Asub(1c) in blood samples. This is a useful technique in the diagnosis of diabetes mellitus. (U.K.)

Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

Energy Technology Data Exchange (ETDEWEB)

Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1979-03-15

The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

Use of Phage Antibodies to Distinguish Closely Related Species of Protozoan Parasites

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Timothy Paget

2000-01-01

Full Text Available Acanthamoeba are typically identified in the laboratory using culture and microscopic observation. In this paper we describe the isolation and specificity of antibody fragments that can be used for the identification of Acanthamoeba. A phage library expressing a large repertoire (approx. 5×109 of antibody fragments was used to generate two libraries one enriched for bacteriophage that exhibit genus specific binding and the other containing bacteriophage that bind specifically to pathogenic Acanthamoeba. Individual clones were isolated on the basis of binding by ELISA, and then flowcytometry and immunofluorescence were used for further characterisation. Four monoclonal antibodies were isolated, specific for Acanthamoeba at the generic level with clone HPPG6 exhibiting the highest level of binding. Furthermore clone HPPG55 was specific for pathogenic species of Acanthamoeba.

Genome-wide analysis of disease progression in age-related macular degeneration.

Science.gov (United States)

Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

2018-03-01

Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

Loss of autonoetic consciousness of recent autobiographical episodes and accelerated long-term forgetting in a patient with previously unrecognized glutamic acid decarboxylase antibody related limbic encephalitis

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Juri-Alexander eWitt

2015-06-01

Full Text Available We describe a 35-year old male patient presenting with depressed mood and emotional instability who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic consciousness regarding autobiographical memories of the last three years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left > right. Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over six months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit vocational reintegration was successfully in progress.In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with

The impact of peer relations on academic progress in junior high

NARCIS (Netherlands)

Lubbers, Miranda J.; Van der Werf, Margaretha P. C.; Snijders, Tom A. B.; Creemers, Bert P. M.; Kuyper, Hans

2006-01-01

The purpose of this study is to examine whether peer relations within classrooms were related to students' academic progress, and if so, whether this can be explained by students' relatedness and engagement, in line with Connell and Wellborn's self-system model. We analyzed data of 18,735 students

Detection of anti-lactoferrin antibodies and anti-myeloperoxidase antibodies in autoimmune hepatitis: a retrospective study.

Science.gov (United States)

Tan, Liming; Zhang, Yuhong; Peng, Weihua; Chen, Juanjuan; Li, Hua; Ming, Feng

2014-01-01

Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH.

Immunoscintigraphy of ovarian carcinoma using OC 125 monoclonal antibody

International Nuclear Information System (INIS)

Park, Sang Yoon

1990-03-01

Immunoscintigraphy (ISG) with I-131 labeled OC 125 F (ab')2 fragments was studied in 7 patients for primary diagnosis and follow up of ovarian cancer. Total body planar photoscans with a scintillation camera were performed three to seven days after antibody application and results were compared with operation and/or computed tomography (CT) examination. By the region of interest technique, the tumor to background ratio was calaulated in vivo. Results are as follows. 1) The sensitivity of ISG and CT for detection of 14 tumor sites which were confirmed with histopathology were 100 % and 57.1 % and the sensitivity for the detection of omental metastasis were 100 % and 20 % respectively. 2) There were no correlation between the serum CA 125 levels and tumor to background antibody uptake ratio. 3) Tumor to background antibody uptake ratio were progressively increased from day 3 to day 7. (author)

γ-Synuclein antibodies have neuroprotective potential on neuroretinal cells via proteins of the mitochondrial apoptosis pathway.

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Corina Wilding

Full Text Available The family of synuclein proteins (α, β and γ are related to neurodegenerative disease e.g. Parkinson disease and Morbus Alzheimer. Additionally, a connection between γ-synuclein and glaucoma, a neurodegenerative disease characterized by a progressive loss of retinal ganglion cells, which finally leads to blindness, exists. The reason for the development of glaucoma is still unknown. Recent studies evaluating the participation of immunological components, demonstrate complex changed antibody reactivities in glaucoma patients in comparison to healthy people, showing not only up-regulations (e.g. alpha-fodrin antibody but also down-regulations (e.g. γ-synuclein antibody of antibodies in glaucoma patients. Up-regulated antibodies could be auto-aggressive, but the role of down-regulated antibodies is still unclear. Previous studies show a significant influence of the serum and the antibodies of glaucoma patients on protein expression profiles of neuroretinal cells. The aim of this study was to investigate the effect of γ-synuclein antibody on the viability and reactive oxygen species levels of a neuroretinal cell line (RGC-5 as well as their interaction with cellular proteins. We found a protective effect of γ-synuclein antibody resulting in an increased viability (up to 15% and decreased reactive oxygen species levels (up to -12% of glutamate and oxidative stressed RGC-5. These can be traced back to anti-apoptotic altered protein expressions in the mitochondrial apoptosis pathway indicated by mass spectrometry and validated by microarray analysis such as active caspase 3, bcl-2 associated-x-protein, S100A4, voltage-dependent anion channel, extracellular-signal-regulated-kinase (down-regulated and baculoviral IAP repeat-containing protein 6, phosphorylated extracellular-signal-regulated-kinase (up-regulated. These changed protein expression are triggered by the γ-synuclein antibody internalization of RGC-5 we could see in immunohistochemical

Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

DEFF Research Database (Denmark)

Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M

2008-01-01

OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...... glucose tolerance test (P insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0...

Recent progress in safety-related applications of reactor noise analysis

International Nuclear Information System (INIS)

Hirota, Jitsuya; Shinohara, Yoshikuni; Saito, Keiichi

1982-01-01

Recent progress in safety-related applications of reactor noise analysis is reviewed, mainly referring to various papers presented at the Third Specialists' Meeting on Reactor Noise (SMORN-III) held in Tokyo in 1981. Advances in application of autoregressive model, coherence analysis and pattern recognition technique are significant since SMORN-II in 1977. Development of reactor diagnosis systems based on noise analysis is in progress. Practical experiences in the safety-related applications to power plants are being accumulated. Advances in quantitative monitoring of vibration of internal structures in PWR and diagnosis of core stability and control system characteristics in BWR are notable. Acoustic methods are also improved to detect sodium boiling in LMFBR. The Reactor Noise Analysis Benchmark Test performed by Japan in connection with SMORN-III is successful so that it is possible to proceed to the second stage of the benchmark test. (author)

Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

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Dimiter S. Dimitrov

2009-11-01

Full Text Available Several human monoclonal antibodies (hmAbs and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i antibodies in HIV-1-infected patients (X5 is a CD4i antibody as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and

S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

DEFF Research Database (Denmark)

Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

2015-01-01

, decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts...

Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.

Science.gov (United States)

Alvarado-Vazquez, P A; Morado-Urbina, C E; Castañeda-Corral, G; Acosta-Gonzalez, R I; Kitaura, H; Kimura, K; Takano-Yamamoto, T; Jiménez-Andrade, J M

2015-01-01

Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 μg/5 μL per joint), isotype control (rat IgG 10 μg/5 μL per joint) or PBS (5 μl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Emerging psychiatric syndromes associated with antivoltage-gated potassium channel complex antibodies.

Science.gov (United States)

Prüss, Harald; Lennox, Belinda R

2016-11-01

Antibodies against the voltage-gated potassium channel (VGKC) were first recognised as having a potential pathogenic role in disorders of the central nervous system in 2001, with VGKC antibodies described in patients with limbic encephalitis, and the subsequent seminal paper describing the clinical phenotype and immunotherapy treatment responsiveness in 13 patients with VGKC antibodies and limbic encephalitis in 2004. These initial case descriptions were of a progressive neuropsychiatric syndrome with abnormalities of mood, sleep and cognition recognised alongside the neurological symptoms of seizures and autonomic instability. The clinical syndromes associated with VGKC complex (VGKCC) antibodies have broadened considerably over the last 15 years, with multiple cases of more restricted 'formes fruste' presentations associated with VGKCC antibodies being described. However, the relevance of antibodies in these cases has remained controversial. The understanding of the pathogenic nature of VGKC antibodies has further advanced since 2010 with the discovery that VGKC antibodies are not usually antibodies against the VGKC subunits themselves, but instead to proteins that are complexed with the potassium channel, in particular leucine-rich, glioma-inactivated protein 1 (LGI1) and contactin-associated protein 2 (Caspr2). Antibodies against these proteins have been associated with particular, although overlapping, clinical phenotypes, each also including neuropsychiatric features. Our aim is to critically review the association between VGKCC, LGI1 and Caspr2 antibodies with isolated psychiatric presentations-with a focus on cognitive impairment, mood disorders and psychosis. We recommend that screening for VGKCC, LGI1 and Caspr2 antibodies be considered for those with neuropsychiatric presentations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

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de Beaufort Carine

2010-09-01

Full Text Available Abstract Background To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative for pancreatic autoantibodies [islet cell autoantibodies(ICA, glutamic acid decarboxylase antibodies (GADA and insulinoma-associated antigen-2 antibodies (IA-2A]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results Twenty-four patients (9.1% tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002, lower blood glucose (P = 0.004, received less insulin (P = 0.05 and had lower HbA1c (P = 0.02 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8 by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.

In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology

DEFF Research Database (Denmark)

Herwerth, Marina; Kalluri, Sudhakar Reddy; Srivastava, Rajneesh

2016-01-01

IgG autoantibodies against aquaporin-4 (AQP4), an astrocytic water channel. Antibodies against AQP4 can damage astrocytes via complement, but NMO histopathology also shows demyelination, and - importantly - axon injury, which may determine permanent deficits following NMO relapses. The dynamics...... antibodies in mice. RESULTS: We found that human AQP4 antibodies caused acute astrocyte depletion with initial oligodendrocyte survival. Within two hours of antibody application, we observed secondary axon injury in the form of progressive swellings. Astrocyte toxicity and axon damage were dependent on AQP4...... antibody concentration and complement, specifically C1q. INTERPRETATION: In vivo imaging of the spinal cord reveals the swift development of NMO-related acute axon injury following AQP4 antibody-mediated astrocyte depletion. This approach will be useful in studying the mechanisms underlying the spread...

New Approaches for Early Detection of Breast Tumor Invasion or Progression

National Research Council Canada - National Science Library

Man, Yan-Gao

2003-01-01

To assess interactions between epithelial (EP) and myoepithelial (ME) cells in association with breast tumor progression and invasion, a double immunostaining technique with antibodies to smooth muscle actin (SMA...

New research progress on the epidemiology of age-related macular degeneration

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Ming-Xing Wu

2015-02-01

Full Text Available Age-related macular degeneration(AMDis a kind of age-related blinding degenerative fundus lesions, totally about 30 million patients suffering from AMD all over the world, with about 500 000 people blind for it yearly. As the development of economy and the aging of the population intensified, incidence of AMD indicates a trend of rising year by year, being the third major cause of blindness in our country. At present, the pathogenesis of AMD is not fully clear, as reported it may be related to oxidative stress, inflammatory immune response, VEGF and genetic manipulation. Clinical treatments mainly include photodynamic therapy, drug therapy, radiation therapy, laser photocoagulaory operation, the pupil warm treatments, Chinese medicine and intravitreous injection VEGF antagonists such as Ranibizumab, Conbercept and so on. In this issue, we mainly expound on the progress in the epidemiological studies of AMD, especially elaborate the progress made on genetic manipulation in recent years.

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

Science.gov (United States)

Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

2017-01-01

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

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Wen-Yang Tsai

2017-07-01

Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

Probable C4d-negative accelerated acute antibody-mediated rejection due to non-HLA antibodies.

Science.gov (United States)

Niikura, Takahito; Yamamoto, Izumi; Nakada, Yasuyuki; Kamejima, Sahoko; Katsumata, Haruki; Yamakawa, Takafumi; Furuya, Maiko; Mafune, Aki; Kobayashi, Akimitsu; Tanno, Yudo; Miki, Jun; Yamada, Hiroki; Ohkido, Ichiro; Tsuboi, Nobuo; Yamamoto, Hiroyasu; Yokoo, Takashi

2015-07-01

We report a case of probable C4d-negative accelerated acute antibody-mediated rejection due to non-HLA antibodies. A 44 year-old male was admitted to our hospital for a kidney transplant. The donor, his wife, was an ABO minor mismatch (blood type O to A) and had Gitelman syndrome. Graft function was delayed; his serum creatinine level was 10.1 mg/dL at 3 days after transplantation. Open biopsy was performed immediately; no venous thrombosis was observed during surgery. Histology revealed moderate peritubular capillaritis and mild glomerulitis without C4d immunoreactivity. Flow cytometric crossmatching was positive, but no panel-reactive antibodies against HLA or donor-specific antibodies (DSAbs) to major histocompatibility complex class I-related chain A (MICA) were detected. Taken together, we diagnosed him with probable C4d-negative accelerated antibody-mediated rejection due to non-HLA, non-MICA antibodies, the patient was treated with steroid pulse therapy (methylprednisolone 500 mg/day for 3 days), plasma exchange, intravenous immunoglobulin (40 g/body), and rituximab (200 mg/body) were performed. Biopsy at 58 days after transplantation, at which time S-Cr levels were 1.56 mg/dL, found no evidence of rejection. This case, presented with a review of relevant literature, demonstrates that probable C4d-negative accelerated acute AMR can result from non-HLA antibodies. © 2015 Asian Pacific Society of Nephrology.

Antithyroid microsomal antibody

Science.gov (United States)

Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked with an increased risk ...

High Grade Glioma Mimicking Voltage Gated Potassium Channel Complex Associated Antibody Limbic Encephalitis

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Dilan Athauda

2014-01-01

Full Text Available Though raised titres of voltage gated potassium channel (VGKC complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE. This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis.

Science.gov (United States)

Athauda, Dilan; Delamont, R S; Pablo-Fernandez, E De

2014-01-01

Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

Antibody-mediated immunotherapy against chronic hepatitis B virus infection.

Science.gov (United States)

Gao, Ying; Zhang, Tian-Ying; Yuan, Quan; Xia, Ning-Shao

2017-08-03

The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogs, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus. As an alternative strategy, immunotherapy with HBsAg-specific antibodies has shown some direct HBsAg suppression effects in several preclinical and clinical trial studies. However, most described previously HBsAg-specific antibodies only had very short-term HBsAg suppression effects in CHB patients and animal models mimicking persistent HBV infection. More-potent antibodies with long-lasting HBsAg clearance effects are required for the development of the clinical application of antibody-mediated immunotherapy for CHB treatment. Our recent study described a novel mAb E6F6 that targets a unique epitope on HBsAg. It could durably suppress the levels of HBsAg and HBV DNA via Fcγ receptor-dependent phagocytosis in vivo. In this commentary, we summarize the current research progress, including the therapeutic roles and mechanisms of antibody-mediated HBV clearance as well as the epitope-determined therapeutic potency of the antibody. These insights may provide some clues and guidance to facilitate the development of therapeutic antibodies against persistent viral infection.

Radiolabeled monoclonal antibodies: a review

International Nuclear Information System (INIS)

Toledo e Souza, I.T. de; Okada, H.

1990-05-01

Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author) [pt

Relative susceptibility of Giardia muris trophozoites to killing by mouse antibodies of different isotypes.

Science.gov (United States)

Heyworth, M F

1992-02-01

The aim of this work was to examine the ability of mouse IgA, IgG, and IgM anti-Giardia antibodies to kill Giardia muris trophozoites in the presence and absence of complement. Using a 2-color flow cytometry assay, binding of antibody to trophozoites was assessed with fluorescein-conjugated anti-mouse immunoglobulin, and percentages of killed trophozoites were quantified by staining with propidium iodide. Trophozoites were killed in the presence of complement by IgG3 and IgM anti-trophozoite monoclonal antibodies. Anti-trophozoite IgA, obtained from the intestinal lumen of G. muris-infected BALB/c mice, became bound to trophozoites in vitro but did not kill these organisms in the presence or absence of complement. The results suggest that clearance of G. muris infection by intestinal IgA directed against G. muris trophozoites does not involve antibody-dependent killing of trophozoites in the intestinal lumen.

Antiprothrombin Antibodies

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Polona Žigon

2015-05-01

Full Text Available In patients with the antiphospholipid syndrome (APS, the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes thrombosis and pregnancy complications. The most frequent antigenic target of antiphospholipid antibodies are phospholipid bound β2-glycoprotein 1 (β2GPI and prothrombin. The international classification criteria for APS connect the occurrence of thrombosis and/or obstetric complications together with the persistence of lupus anticoagulant, anti-cardiolipin antibodies (aCL and antibodies against β2GPI (anti-β2GPI into APS. Current trends for the diagnostic evaluation of APS patients propose determination of multiple antiphospholipid antibodies, among them also anti-prothrombin antibodies, to gain a common score which estimates the risk for thrombosis in APS patients. Antiprothrombin antibodies are common in APS patients and are sometimes the only antiphospholipid antibodies being elevated. Methods for their determination differ and have not yet been standardized. Many novel studies confirmed method using phosphatidylserine/prothrombin (aPS/PT ELISA as an antigen on solid phase encompass higher diagnostic accuracy compared to method using prothrombin alone (aPT ELISA. Our research group developed an in-house aPS/PT ELISA with increased analytical sensitivity which enables the determination of all clinically relevant antiprothrombin antibodies. aPS/PT exhibited the highest percentage of lupus anticoagulant activity compared to aCL and anti-β2GPI. aPS/PT antibodies measured with the in-house method associated with venous thrombosis and presented the strongest independent risk factor for the presence of obstetric complications among all tested antiphospholipid antibodies. 

Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients.

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Pochechueva, Tatiana; Alam, Shahidul; Schötzau, Andreas; Chinarev, Alexander; Bovin, Nicolai V; Hacker, Neville F; Jacob, Francis; Heinzelmann-Schwarz, Viola

2017-02-10

Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets. We found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells. Our data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.

Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.

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Nobuhara, Chloe K; DeVos, Sarah L; Commins, Caitlin; Wegmann, Susanne; Moore, Benjamin D; Roe, Allyson D; Costantino, Isabel; Frosch, Matthew P; Pitstick, Rose; Carlson, George A; Hock, Christoph; Nitsch, Roger M; Montrasio, Fabio; Grimm, Jan; Cheung, Anne E; Dunah, Anthone W; Wittmann, Marion; Bussiere, Thierry; Weinreb, Paul H; Hyman, Bradley T; Takeda, Shuko

2017-06-01

The clinical progression of Alzheimer disease (AD) is associated with the accumulation of tau neurofibrillary tangles, which may spread throughout the cortex by interneuronal tau transfer. If so, targeting extracellular tau species may slow the spreading of tau pathology and possibly cognitive decline. To identify suitable target epitopes, we tested the effects of a panel of tau antibodies on neuronal uptake and aggregation in vitro. Immunodepletion was performed on brain extract from tau-transgenic mice and postmortem AD brain and added to a sensitive fluorescence resonance energy transfer-based tau uptake assay to assess blocking efficacy. The antibodies reduced tau uptake in an epitope-dependent manner: N-terminal (Tau13) and middomain (6C5 and HT7) antibodies successfully prevented uptake of tau species, whereas the distal C-terminal-specific antibody (Tau46) had little effect. Phosphorylation-dependent (40E8 and p396) and C-terminal half (4E4) tau antibodies also reduced tau uptake despite removing less total tau by immunodepletion, suggesting specific interactions with species involved in uptake. Among the seven antibodies evaluated, 6C5 most efficiently blocked uptake and subsequent aggregation. More important, 6C5 also blocked neuron-to-neuron spreading of tau in a unique three-chamber microfluidic device. Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Cytomegalovirus Antibody Elevation in Bipolar Disorder: Relation to Elevated Mood States

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A. R. Prossin

2015-01-01

Full Text Available The neurobiology of mood states is complicated by exposure to everyday stressors (e.g., psychosocial, ubiquitous environmental infections like CMV, each fluctuating between latency and reactivation. CMV reactivation induces proinflammatory cytokines (e.g., TNF-α associated with induction of neurotoxic metabolites and the presence of mood states in bipolar disorder (BD. Whether CMV reactivation is associated with bipolar diagnoses (trait or specific mood states is unclear. We investigated 139 BD type I and 99 healthy controls to determine if concentrations of IgG antibodies to Herpesviridae (e.g., CMV, HSV-1, and HSV-2 were associated with BD-I diagnosis and specific mood states. We found higher CMV antibody concentration in BD-I than in healthy controls (T234=3.1, Puncorr=0.002; Pcorr=0.006 but no difference in HSV-1 (P>0.10 or HSV-2 (P>0.10. Compared to euthymic BD-I volunteers, CMV IgG was higher in BD-I volunteers with elevated moods (P0.10. While relationships presented between BD-I diagnosis, mood states, and CMV antibodies are encouraging, they are limited by the study’s cross sectional nature. Nevertheless, further testing is warranted to replicate findings and determine whether reactivation of CMV infection exacerbates elevated mood states in BD-I.

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

Institute of Scientific and Technical Information of China (English)

Qi-Guang Shi; Zhi-Hong Wang; Xiao-Wei Ma; Da-Qi Zhang; Chun-Sheng Yang; Fu-Dong Shi; Li Yang

2012-01-01

Objective To evaluate the frequency,distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor (AChR) in patients with myasthenia gravis (MG).Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG (OMG) (n =90) and generalized MG (GMG) patients (n =110).The fetaltype (2α∶ β∶ γ∶ δ) and adult-type (2α∶ β∶ ε∶ δ) AChR were used as antigens,and their relevance to disease presentation was assessed.Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined,with 14 having serum specific to the AChR-γ subunit,and 22 to the AChR-ε subunit.The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only (P =0.015).Compared with OMG patients,the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG.Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio (OR),1.03;95％ confidence interval (CI),1.01-1.06 and OR,5.09;95％ CI,2.23-11.62].Conclusion Using both fetal-and adulttype AChRs as the antigens may be more sensitive than using either subtype.Patients with serum specific to both isoforms are at a greater risk of progressing to GMG.Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

Radioimmunoassays and related procedures in the diagnosis of parasitic infections

International Nuclear Information System (INIS)

Dessaint, J.P.; Cesbron, J.Y.; Lutsch, C.; Nogueira-Queiroz, J.A.; Capron, A.

1986-01-01

Immunological tests for the diagnosis of parasitic infections have long been used, yet the marked variability in seroreactivity of infected patients is still a challenge to immunoparasitologists. In the case of helminth parasites, especially schistosomes and filariae, immunoassays have benefited by numerous advances in the characterization and purification of antigens and by the use of monoclonal antibodies. The identification of functional antigens allows the detection of putative protective (or blocking) antibody responses by competitive RIAs using monoclonal antibodies in schistosomiasis. While progress has been made in the investigation of immunity in man, immunoassays for antibodies do not accurately correlate with parasite load, especially at lower antibody responses or after chemotherapy. Immunoassays for circulating parasite antigens have received much attention in recent years. Immunoradiometric assays and related procedures using infection sera or monoclonal antibodies are now being investigated in field conditions. Cross-reactions among circulating antigens from different parasites can decrease the specificity of such assays, whereas circulating immune complexes can interfere with the test. The recent use of RIAs to measure parasite antigens in the urine of patients with schistosomiasis or filariasis appears a promising approach. (author)

Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 ...

African Journals Online (AJOL)

Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected untreated children in Kenya; implication for immunodeficiency and AIDS progression. Washingtone Ochieng, Dorington Ogoyi, Francis J Mulaa, Simon Ogola, Rachel Musoke, Moses G Otsyula ...

Antibody Maturation in Trypanosoma cruzi-Infected Rats

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Marcipar, Iván S.; Risso, Marikena G.; Silber, Ariel M.; Revelli, Silvia; Marcipar, Alberto J.

2001-01-01

The study of antibody avidity changes during infection has improved the understanding of the pathologic processes involved in several infectious diseases. In some infections, like toxoplasmosis, this information is being used for diagnostic purposes. Results of the evolution of antibody avidity for different specific antigens in Trypanosome cruzi-infected rats are presented. A Western blotting technique, combined with avidity analysis to identify antigens that elicit high-avidity antibodies, is suggested. In this system, antibodies showed high avidity values only during the chronic phase of infection and only in relation to antibodies against 21-, 33-, 41-, 42-, 56-, 58-, 66-, and 72-kDa antigens. Finally, a 97-kDa T. cruzi antigen, which was recognized by high-avidity antibodies and occurred in noninfected rats, was identified. These results allow us to evaluate the different antigens in chagasic infection. Our results show that with the correct choice of antigen it is possible to detect differences in maturation of antibodies and to discriminate, in an experimental model, between recent (acute) and chronic infections. PMID:11427430

Human antibody technology and the development of antibodies against cytomegalovirus.

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Ohlin, Mats; Söderberg-Nauclér, Cecilia

2015-10-01

Cytomegalovirus (CMV) is a virus that causes chronic infections in a large set of the population. It may cause severe disease in immunocompromised individuals, is linked to immunosenescence and implied to play an important role in the pathogenesis of cardiovascular diseases and cancer. Modulation of the immune system's abilities to manage the virus represent a highly viable therapeutic option and passive immunotherapy with polyclonal antibody preparations is already in clinical use. Defined monoclonal antibodies offer many advantages over polyclonal antibodies purified from serum. Human CMV-specific monoclonal antibodies have consequently been thoroughly investigated with respect to their potential in the treatment of diseases caused by CMV. Recent advances in human antibody technology have substantially expanded the breadth of antibodies for such applications. This review summarizes the fundamental basis for treating CMV disease by use of antibodies, the basic technologies to be used to develop such antibodies, and relevant human antibody specificities available to target this virus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antimitochondrial antibody

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... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

Purification of immunoreactive radiolabeled moniclonal antibodies with anti-iodiotypic moniclonal antibodies

International Nuclear Information System (INIS)

Temponi, M.; Pupa, S.; Ferrone, S.

1990-01-01

A method is described to purify immunoreactive moniclonal antibodies from radiolabeled monoclonal antibody preparations. The method is based on incubation of radiolabeled monoclonal antibodies with insolubilized anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of monoclonal antibodies to be purified an elution of bound monoclonal antibodies with a low pH buffer. The immunoreactive fraction of the purified monoclonal antibodies was at least 82%; the yeald was at least 73%. The purification procedure did not cause any detectable change in the affinity constant of the eluted monoclonal antibodies. The method is simple and rapid; the requirement for anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of the antibodies to be purified is not likely to represent a major limitation in the broad application of the present method, since the hybridoma technology has greatly facilitated the development of anti-idiotypic monoclonal antibodies. (author). 12 refs.; 4 figs.; 1 tab

A generalized quantitative antibody homeostasis model: maintenance of global antibody equilibrium by effector functions.

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Prechl, József

2017-11-01

The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]= K D . This zone corresponds to the biologically relevant K D range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher-order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a

Thyroid failure in the elderly: microsomal antibodies as discriminant for therapy

International Nuclear Information System (INIS)

Rosenthal, M.J.; Hunt, W.C.; Garry, P.J.; Goodwin, J.S.

1987-01-01

Thyrotropin (thyroid-stimulating hormone [TSH]) levels were elevated above 4.0 mU/L (μU/mL) in serum samples from 13.2% of 258 healthy elderly subjects. To investigate the natural history of progressive thyroid failure, serial thyroid functions were measured using radioimmunoassay for four years in 26 of these subjects with elevated TSH levels. In one third of these subjects, biochemical thyroid failure developed within the course of the study. All subjects with initial TSH levels above 20 mU/L (μU/mL), and 80% of those with high-titer thyroid antimicrosomal antibodies (regardless of initial TSH level), became overtly hypothyroid. Compared with subjects with high-titer antibody, those with antibody titer less than 1:1600 had lower TSH and higher thyroxine levels, and thyroid failure developed in none during the study. These results suggest that among older patients with isolated elevations of the TSH level, only those with markedly elevated TSH levels or high-titer antimicrosomal antibodies should be prophylactically treated with levothyroxine sodium replacement

Antibodies immobilized on magnetic particles for RIA and IRMA of thyroid related hormones

International Nuclear Information System (INIS)

Wayan, R.S.; Djayusman, D.S.

1996-01-01

In Indonesia radioimmunoassay kits on the magnetic method of separation need to be imported and are very expensive. Local production of these kits would be economical. Different types of magnetic particles have been used for immobilizing antibodies for use in RIA of T 3 , T 4 , IRMA-TSH as well as neonatal IRMA-TSH. The particles studied here include magnetic cellulose (SCIPAC, U.K.), magnetite (Hungary), Silanized Iron Oxide (China) and Latex-M. Various parameters have been studied in order to optimize the antibody immobilization procedures as well as the assays based on these immunoadsorbents. The assays developed by us have been compared with those obtained with commercial kits from Amersham, NETRIA and DPC. The study done in this work includes immobilization of second antibodies for RIA of T 4 and immobilization of anti-TSH for IRMA-TSH. Among several different magnetic particles studied in this work, magnetite and silanized iron oxide were found to be satisfactory on account of the simplicity of immobilization, high binding capacity and the low non specific binding. A good assay performance in the case of RIA T 3 and T 4 was obtained using second antibodies immobilized magnetic particles. However, the quality of first antibodies is found to play an important role on the sensitivity and precision of the assay. Good correlation has been obtained with Amersham kit (y = 1.06x - 0.12 and r = 0.987). Assay performance of IRMA-TSH using in-house prepared anti-TSH immobilized magnetic particles is also found to be comparable with Amersham, NETRIA and DPC kits. (author). 4 refs, 6 figs, 1 tab

Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients.

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Pathak, Surajit; S, Sushmitha; Banerjee, Antara; Marotta, Francesco; Gopinath, Madhumala; Murugesan, Ramachandran; Zhang, Hong; B, Bhavani; Girigoswami, Agnishwar; Sollano, Jose; Sun, Xiao-Feng

2018-01-26

Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS . Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS , validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

Progress on study of nuclear data theory and related fields at the Theory Group of CNDC

Energy Technology Data Exchange (ETDEWEB)

Zhigang, Ge [China Nuclear Data Center, CIAE (China)

1996-06-01

The Theory Group of CNDC (China Nuclear Data Center) has made a lot of progress in nuclear reaction theory and its application as well as many other related fields in 1995. The recent progress in nuclear reaction theory study and its applications, the recent progress in the nuclear data calculation and related code development are introduced. The production rate of radioactive nuclear beam induced by 70 MeV protons on {sup 72}Ge target were calculated. The calculated results are presented.

Customizing monoclonal antibodies for the treatment of methamphetamine abuse: current and future applications.

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Peterson, Eric C; Gentry, W Brooks; Owens, S Michael

2014-01-01

Monoclonal antibody-based medications designed to bind (+)-methamphetamine (METH) with high affinity are among the newest approaches to the treatment of METH abuse and the associated medical complications. The potential clinical indications for these medications include treatment of overdose, reduction of drug dependence, and protection of vulnerable populations from METH-related complications. Research designed to discover and conduct preclinical and clinical testing of these antibodies suggests a scientific vision for how intact monoclonal antibody (mAb) (singular and plural) or small antigen-binding fragments of mAb could be engineered to optimize the proteins for specific therapeutic applications. In this review, we discuss keys to success in this development process including choosing predictors of specificity, efficacy, duration of action, and safety of the medications in disease models of acute and chronic drug abuse. We consider important aspects of METH-like hapten design and how hapten structural features influence specificity and affinity, with an example of a high-resolution X-ray crystal structure of a high-affinity antibody to demonstrate this structural relationship. Additionally, several prototype anti-METH mAb forms such as antigen-binding fragments and single-chain variable fragments are under development. Unique, customizable aspects of these fragments are presented with specific possible clinical indications. Finally, we discuss clinical trial progress of the first in kind anti-METH mAb, for which METH is the disease target instead of vulnerable central nervous system networks of receptors, binding sites, and neuronal connections. © 2014 Elsevier Inc. All rights reserved.

A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

International Nuclear Information System (INIS)

Jusko, Todd A.; De Roos, Anneclaire J.; Schwartz, Stephen M.; Paige Lawrence, B.; Palkovicova, Lubica; Nemessanyi, Tomas; Drobna, Beata; Fabisikova, Anna; Kocan, Anton; Sonneborn, Dean; Jahnova, Eva; Kavanagh, Terrance J.; Trnovec, Tomas; Hertz-Picciotto, Irva

2010-01-01

Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

Energy Technology Data Exchange (ETDEWEB)

Jusko, Todd A., E-mail: juskota@niehs.nih.gov [Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, 111 T.W. Alexander Dr, Rall Bldg 101, Rm A361, Research Triangle Park, NC 27709-2233 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); De Roos, Anneclaire J.; Schwartz, Stephen M. [Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Paige Lawrence, B. [Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (United States); Palkovicova, Lubica [Department of Environmental Medicine, Slovak Medical University, Bratislava (Slovakia); Nemessanyi, Tomas [Department of Immunology and Immunotoxicology, Slovak Medical University, Bratislava (Slovakia); Drobna, Beata; Fabisikova, Anna; Kocan, Anton [Department of Toxic Organic Pollutants, Slovak Medical University, Bratislava (Slovakia); Sonneborn, Dean [Department of Public Health Sciences, University of California, Davis, CA (United States); Jahnova, Eva [Department of Immunology and Immunotoxicology, Slovak Medical University, Bratislava (Slovakia); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA (United States); Trnovec, Tomas [Department of Toxic Organic Pollutants, Slovak Medical University, Bratislava (Slovakia); Hertz-Picciotto, Irva [Department of Public Health Sciences, University of California, Davis, CA (United States)

2010-05-15

Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: A case control study

Directory of Open Access Journals (Sweden)

Ruff P

2006-09-01

Full Text Available Abstract Background Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. Methods We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity(n = 88, the cervix(n = 53, the prostate(n = 66, Hodgkin lymphoma(n = 83, non-Hodgkin lymphoma(n = 80, multiple myeloma(n = 94 or leukaemia(n = 203. For comparison, patients with other cancers(n = 95 or cardiovascular disease(n = 101 were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. Results There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0

Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

Science.gov (United States)

Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

2014-09-01

Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (ptreatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

Relation between task complexity and variability of procedure progression during an emergency operation

International Nuclear Information System (INIS)

Kim, Yochan; Park, Jinkyun; Jung, Wondea

2013-01-01

Highlights: • The relation between task complexity and the variability of procedure progression was investigated. • The two quantitative measures, TACOM and VPP, were applied to this study. • The task complexity was positively related with the operator’s procedural variability. • The VPP measure can be useful for explaining the operator’s behaviors. - Abstract: In this study, the relation between task complexity and variability of procedure progression during an emergency operation was investigated by comparing the two quantitative measures. To this end, the TACOM measure and VPP measure were applied to evaluate the complexity of tasks and variability of procedure progression, respectively. The TACOM scores and VPP scores were obtained for 60 tasks in the OPERA database, and a correlation analysis between two measures and a multiple regression analysis between the sub-measures of the TACOM measure and VPP measure were conducted. The results showed that the TACOM measure is positively associated with the VPP measure, and the abstraction hierarchy complexity mainly affected the variability among the sub-measures of TACOM. From these findings, it was discussed that the task complexity is related to an operator’s procedural variability and VPP measure can be useful for explaining the operator’s behaviors

Sequences of 12 monoclonal anti-dinitrophenyl spin-label antibodies for NMR studies

International Nuclear Information System (INIS)

Leahy, D.J.; Rule, G.S.; Whittaker, M.M.; McConnell, H.M.

1988-01-01

Eleven monoclonal antibodies specific for a spin-labeled dinitrophenyl hapten (DNP-SL) have been produces for use in NMR studies. They have been named AN01 and ANO3-AN12. The stability constants for the association of these antibodies with DNP-SL and related haptens were measured by fluorescence quenching. cDNA clones coding for the heavy and light chains of each antibody and of an additional anti-DNP-SL monoclonal antibody, ANO2, have been isolated. The nucleic acid sequence of the 5' end of each clone has been determined, and the amino acid sequence of the variable regions of each antibody has been deduced from the cDNA sequence. The sequences are relatively heterogeneous, but both the heavy and the light chains of ANO1 and ANO3 are derived from the same variable-region gene families as those of the ANO2 antibody. ANO7 has a heavy chain that is related to that of ANO2, and ANO9 has a related light chain. ANO5 and ANO6 are unrelated to ANO2 but share virtually identical heavy and light chains. Preliminary NMR difference spectra comparing related antibodies show that sequence-specific assignment of resonances is possible. Such spectra also provide a measure of structural relatedness

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization

International Nuclear Information System (INIS)

Kumakura, M.; Kaetsu, I.; Suzuki, M.; Adachi, S.

1983-01-01

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity

[VGKC-complex antibodies].

Science.gov (United States)

Watanabe, Osamu

2013-04-01

Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

Antibodies from plants for bionanomaterials.

Science.gov (United States)

Edgue, Gueven; Twyman, Richard M; Beiss, Veronique; Fischer, Rainer; Sack, Markus

2017-11-01

Antibodies are produced as part of the vertebrate adaptive immune response and are not naturally made by plants. However, antibody DNA sequences can be introduced into plants, and together with laboratory technologies that allow the design of antibodies recognizing any conceivable molecular structure, plants can be used as 'green factories' to produce any antibody at all. The advent of plant-based transient expression systems in particular allows the rapid, convenient, and safe production of antibodies, ranging from laboratory-scale expression to industrial-scale manufacturing. The key features of plant-based production include safety, speed, low cost, and convenience, allowing newcomers to rapidly master the technology and use it to its full advantage. Manufacturing in plants has recently achieved significant milestones and offers more than just an alternative to established microbial and mammalian cell platforms. The use of plants for product development in particular offers the power and flexibility to easily coexpress many different genes, allowing the plug-and-play construction of novel bionanomaterials, perfectly complementing existing approaches based on plant virus-like particles. As well as producing single antibodies for applications in medicine, agriculture, and industry, plants can be used to produce antibody-based supramolecular structures and scaffolds as a new generation of green bionanomaterials that promise a bright future based on clean and renewable nanotechnology applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1462. doi: 10.1002/wnan.1462 For further resources related to this article, please visit the WIREs website. © 2017 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

Estimating Parameters Related to the Lifespan of Passively Transferred and Vaccine-Induced Porcine Reproductive and Respiratory Syndrome Virus Type I Antibodies by Modeling Field Data

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Mathieu Andraud

2018-01-01

Full Text Available The outputs of epidemiological models are strongly related to the structure of the model and input parameters. The latter are defined by fitting theoretical concepts to actual data derived from field or experimental studies. However, some parameters may remain difficult to estimate and are subject to uncertainty or sensitivity analyses to determine their variation range and their global impact on model outcomes. As such, the evaluation of immunity duration is often a puzzling issue requiring long-term follow-up data that are, most of time, not available. The present analysis aims at characterizing the kinetics of antibodies against Porcine Reproductive and Respiratory Syndrome virus (PRRSv from longitudinal data sets. The first data set consisted in the serological follow-up of 22 vaccinated gilts during 21 weeks post-vaccination (PV. The second one gathered the maternally derived antibodies (MDAs kinetics in piglets from three different farms up to 14 weeks of age. The peak of the PV serological response against PRRSv was reached 6.9 weeks PV on average with an average duration of antibodies persistence of 26.5 weeks. In the monitored cohort of piglets, the duration of passive immunity was found relatively short, with an average duration of 4.8 weeks. The level of PRRSv-MDAs was found correlated with the dams’ antibody titer at birth, and the antibody persistence was strongly related to the initial MDAs titers in piglets. These results evidenced the importance of PRRSv vaccination schedule in sows, to optimize the delivery of antibodies to suckling piglets. These estimates of the duration of active and passive immunity could be further used as input parameters of epidemiological models to analyze their impact on the persistence of PRRSv within farms.

Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

Energy Technology Data Exchange (ETDEWEB)

Jin, Hongjun; Zangar, Richard C.

2017-01-17

Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

Antibody Engineering and Therapeutics

Science.gov (United States)

Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

2014-01-01

The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

Prediction of antibody persistency from antibody titres to natalizumab

DEFF Research Database (Denmark)

Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn

2012-01-01

In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

Anti-ribosomal P antibodies related to depression in early clinical course of systemic lupus erythematosus

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Mansoor Karimifar

2013-01-01

Full Text Available Background: Diagnosis and treatment of neuropsychiatric lupus is still a major challenge in clinical practice. We investigated the association between depression and anti-ribosomal P (anti-P antibodies in a sample of Iranian patients with systemic lupus erythematosus (SLE. Materials and Methods: This cross-sectional study was conducted on adult patients with SLE referring to a referral out-patient clinic of rheumatology. Demographic data and clinical data with regards to measuring disease activity with the systemic lupus erythematosus disease activity index were gathered. Anti-P antibodies were measured with the enzyme-linked immunosorbent assay method. Depression severity was measured by the Beck Depression Inventory-II. Results: One hundred patients (80% female and 20% male, age = 34.8 ± 10.9 years were included. Anti-P antibodies were present more frequently in depressed than non-depressed patients (30% vs. 10%, P = 0.015. Depression severity was correlated with anti-P antibodies level only in patients with disease duration of less than 2 years (r = 0.517, P = 0.019. There was no association between the depression severity and disease activity. Binary logistic regression analysis showed age (B = 0.953, CI 95%: 0.914-0.993 and positive anti-P antibodies (B = 4.30, CI 95%: 1.18-15.59 as factors that independently associated with depression. Conclusion: We found an association between depression and presence of anti-P antibodies, and also strong correlation between depression severity and anti-P antibodies level in newly diagnosed SLE patients. Depression severity in newly diagnosed SLE patients may reflect a neuropsychiatric involvement, and in later phases, it is more affected by the chronicity of the disease as well as other environmental factors.

Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication.

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Karl Frontzek

Full Text Available Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE, progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication.

Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.

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Juan Pablo Jaworski

Full Text Available Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig purified from previously infected animals (SHIVIG or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

Monoclonal antibodies for radioimmunodetection of tumours and for targeting

International Nuclear Information System (INIS)

Baldwin, R.W.; Embleton, M.J.; Pimm, M.V.

1983-01-01

A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131 I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour/non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon). Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 anti-body defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

Science.gov (United States)

Yamada, Chisa; Teener, James W; Davenport, Robertson D; Cooling, Laura

2015-10-01

Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management. © 2014 Wiley Periodicals, Inc.

Novel Antibody-Based Proteins for Cancer Immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Fuenmayor, Jaheli; Montaño, Ramon F., E-mail: jfuenmay@ivic.gob.ve [Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas. Caracas, 1020-A (Venezuela, Bolivarian Republic of)

2011-08-19

The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

Changes in avidity and level of immunoglobulin G antibodies to Mycobacterium tuberculosis in sera of patients undergoing treatment for pulmonary tuberculosis

NARCIS (Netherlands)

Arias-Bouda, Lenka M. Pereira; Kuijper, Sjoukje; van der Werf, Anouk; Nguyen, Lan N.; Jansen, Henk M.; Kolk, Arend H. J.

2003-01-01

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity

Glycosylation profiles of therapeutic antibody pharmaceuticals.

Science.gov (United States)

Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

2011-11-01

Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth. Copyright © 2011 Elsevier B.V. All rights reserved.

Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

International Nuclear Information System (INIS)

Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

2007-01-01

Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine

DEFF Research Database (Denmark)

Dodick, David W; Goadsby, Peter J; Silberstein, Stephen D

2014-01-01

BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo-contro...

Association of adiponectin, interleukin (IL)-1ra, inducible protein 10, IL-6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis

DEFF Research Database (Denmark)

Kaas, A; Pfleger, Claudia Christina; Hansen, Lene

2010-01-01

progressers and remitters. Serum concentrations of adiponectin, interleukin (IL)-1ra, inducible protein 10 (IP-10), IL-6 and glutamic acid decarboxylase (GAD), IA-2A and islet-cell antibodies (ICA) were measured at 1, 6 and 12 months. We found that adiponectin concentrations at 1 month predicted disease......The progression of type 1 diabetes after diagnosis is poorly understood. Our aim was to assess the relation of disease progression of juvenile-onset type 1 diabetes, determined by preserved beta cell function the first year after diagnosis, with systemic cytokine concentrations and number...

ROLE OF DIETARY SUPPLEMENTATION IN PREVENTING PROGRESSION OF AGE-RELATED MACULAR DEGENERATION

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N. A. Ermakova

2016-01-01

Full Text Available Age-related macular degeneration (AMD is a chronic, progressive, degenerative eye disease affecting the central retina. It is the leading cause of blindness among individuals of 65 years and older. In the early stage patients have drusen and/or alterations of pigmentation in the macular region. This disease can progress to geographic atrophy and/or choroidal neovascularization. It has been shown that oxidative stress and hypoxia are important in the pathogenesis of AMD. Patients may gain some visual improvement with inhibitors of vascular endothelial growth factor, but complete restoration of visual function is achieved only in small cases. No effective therapies are known for atrophic AMD. Many large observational studies have shown that dietary antioxidant supplementation is beneficial in preventing the progression of AMD from early to late stages. The Age-Related Eye Disease Study (AREDS demonstrated that daily oral supplementation with vitamins C (500 mg and E (400 IU, beta carotene (15 mg, zinc (80 mg and copper (2 mg reduced the risk of progression to advanced AMD by 25% at 5 years. In primary analyses AREDS II failed to show further reduce of this risk by addition of lutein (10 mg and zeaxanthin (2mg, or/and omega-3 long-chain polyunsaturated fatty acids [docosahexaenoic acid (350 mg DHA and eicosapentaenoic acid 650 mg (EPA] to the AREDS formulation. But there was no true placebo group. The simultaneous administration of beta carotene, lutein and zeaxanthin may suppress tissue level of the both laters because of competitive absorption of carotenoids. Subgroup analyses revealed that dietary supplementation with lutein, zeaxanthin and AREDS formulation without beta carotene may reduce the risk of progression to advanced AMD.The LUNA (Lutein nutrition effects measured by autofluorescence study demonstrated that supplementation with lutein (12 mg, zeaxanthin (1 mg, vitamin C (120 mg, vitamin E (17,6 mg, zinc (10 mg, selenium (40 mg resulted

Anti-cyclic citrullinated peptide antibodies – a role in rheumatoid arthritis and the possibility of seroconversion: A focus on abatacept

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N. V. Chichasova

2017-01-01

Full Text Available The detection of anti-cyclic citrullinated peptide (anti-CCP antibodies plays a diagnostic and statistical predictive role in rheumatoid arthritis (RA. The decreased concentration of anti-CCP antibodies or their seroconversion is observed for not all groups of anti-inflammatory drugs. Seropositivity for anti-CCP antibodies is a predictor of the higher efficacy of abatacept (ABC. The possibility of seroconversion of anti-CCP antibodies, like rheumatoid factor, during treatment with ABC is associated with the more pronounced suppression of clinical symptoms of RA activity and progressive joint destruction, with remission achievement in a large proportion of patients.

Thyroid Antibodies

Science.gov (United States)

... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

Boosting antibody developability through rational sequence optimization.

Science.gov (United States)

Seeliger, Daniel; Schulz, Patrick; Litzenburger, Tobias; Spitz, Julia; Hoerer, Stefan; Blech, Michaela; Enenkel, Barbara; Studts, Joey M; Garidel, Patrick; Karow, Anne R

2015-01-01

The application of monoclonal antibodies as commercial therapeutics poses substantial demands on stability and properties of an antibody. Therapeutic molecules that exhibit favorable properties increase the success rate in development. However, it is not yet fully understood how the protein sequences of an antibody translates into favorable in vitro molecule properties. In this work, computational design strategies based on heuristic sequence analysis were used to systematically modify an antibody that exhibited a tendency to precipitation in vitro. The resulting series of closely related antibodies showed improved stability as assessed by biophysical methods and long-term stability experiments. As a notable observation, expression levels also improved in comparison with the wild-type candidate. The methods employed to optimize the protein sequences, as well as the biophysical data used to determine the effect on stability under conditions commonly used in the formulation of therapeutic proteins, are described. Together, the experimental and computational data led to consistent conclusions regarding the effect of the introduced mutations. Our approach exemplifies how computational methods can be used to guide antibody optimization for increased stability.

CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

Science.gov (United States)

Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

2015-09-03

The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

[A spectrum of neurological diseases with anti-VGKC antibody].

Science.gov (United States)

Arimura, Kimiyoshi; Watanabe, Osamu; Nagado, Tatsui

2007-11-01

Anti-VGKC antibody causing peripheral nerve hyperexcitability is already an established clinical entity. Recently, many patients with non-herpetic limbic encephalitis (NHLE) with anti-VGKC antibody have been reported. The characteristic clinical features are low serum Na+ concentration and good response to immunotherapy. Anti-VGK antibody positive NHLE is relatively frequent among immune-mediated NHLE. It is important to know that this disease is responsive to immunotherapy. Furthermore, anti-VGKC antibody is also positive in some intractable epilepsies. These findings suggest that anti-VGKC is correlated with hyperexcitability in both the peripheral and central nervous system and that the spectrum of anti-VGKC antibody syndrome is now expanding.

Studies related to antibody-mediated boron delivery for BNCT

International Nuclear Information System (INIS)

Hawthorne, M.F.; Varadarajan, A.; Paxton, R.J.; Beatty, B.G.; Curtis, F.L.

1992-01-01

Of the many methods of selective boron delivery to tumor presently under consideration the use of boron-labeled tumor-targeted monoclonal antibodies (Mabs) and their immunoreactive fragments appears to offer the most general, but complex, approach. Assuming that tumor cells generally carry 10 6 characteristic antigenic sites of any one type and that there are approximately 10 9 cells per gram of tumor, one calculates that about 600 10 B atoms must be attached to each individual Mab molecule (if all antigenic sites are complexed) for each 10 ppm of 10 B supplied to tumor. Rather than randomly attack IgG Mab molecules with a large number of relatively small boron-containing conjugation reagent molecules the authors have chosen to assemble a series of discrete, precisely synthesized oligomeric reagents ('trailers') each of which contains a fixed number of B-atoms up to approximately 200. These oligomeric reagents would carry a radioactive or fluorescent group for analytical purposes attached to a terminal-NH 2 group of their chain and the remaining -COOH terminus would be free for conjugation with the lysine var-epsilon-NH 2 groups of Mab protein. Two types of oligomeric trailer reagents are envisioned; hydrophilic peptides and polyamides

Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats

NARCIS (Netherlands)

Toropainen, Maija; Saarinen, Leena; Vidarsson, Gestur; Käyhty, Helena

2006-01-01

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and

Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

Directory of Open Access Journals (Sweden)

Gaetana Paolella

Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients

DEFF Research Database (Denmark)

Meyer, C N; Svenson, M; Schade Larsen, C

2000-01-01

of HIV-infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP-1alpha and rMIP-1beta, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both...... chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL-2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL-2. Hence, circulating factors, including antibodies MIP-1alpha/MIP-1beta...

Radiolabeled antibody imaging

International Nuclear Information System (INIS)

Wahl, R.L.

1987-01-01

Radiolabeled antibodies, in particular monoclonal antibodies, offer the potential for the specific nuclear imaging of malignant and benign diseases in man. If this imaging potential is realized, they may also have a large role in cancer treatment. This paper reviews: (1) what monoclonal antibodies are and how they differ from polyclonal antibodies, (2) how they are produced and radiolabeled, (3) the results of preclinical and clinical trials in cancer imaging, including the utility of SPECT and antibody fragments, (4) the role of antibodies in the diagnosis of benign diseases, (5) alternate routes of antibody delivery, (6) the role of these agents in therapy, and (7) whether this technology ''revolutionizes'' the practice of nuclear radiology, or has a more limited complementary role in the imaging department

Defining process design space for monoclonal antibody cell culture.

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Abu-Absi, Susan Fugett; Yang, LiYing; Thompson, Patrick; Jiang, Canping; Kandula, Sunitha; Schilling, Bernhard; Shukla, Abhinav A

2010-08-15

The concept of design space has been taking root as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. During mapping of the process design space, the multidimensional combination of operational variables is studied to quantify the impact on process performance in terms of productivity and product quality. An efficient methodology to map the design space for a monoclonal antibody cell culture process is described. A failure modes and effects analysis (FMEA) was used as the basis for the process characterization exercise. This was followed by an integrated study of the inoculum stage of the process which includes progressive shake flask and seed bioreactor steps. The operating conditions for the seed bioreactor were studied in an integrated fashion with the production bioreactor using a two stage design of experiments (DOE) methodology to enable optimization of operating conditions. A two level Resolution IV design was followed by a central composite design (CCD). These experiments enabled identification of the edge of failure and classification of the operational parameters as non-key, key or critical. In addition, the models generated from the data provide further insight into balancing productivity of the cell culture process with product quality considerations. Finally, process and product-related impurity clearance was evaluated by studies linking the upstream process with downstream purification. Production bioreactor parameters that directly influence antibody charge variants and glycosylation in CHO systems were identified.

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

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Million, Matthieu; Bardin, Nathalie; Bessis, Simon; Nouiakh, Nadia; Douliery, Charlaine; Edouard, Sophie; Angelakis, Emmanouil; Bosseray, Annick; Epaulard, Olivier; Branger, Stéphanie; Chaudier, Bernard; Blanc-Laserre, Karine; Ferreira-Maldent, Nicole; Demonchy, Elisa; Roblot, France; Reynes, Jacques; Djossou, Felix; Protopopescu, Camelia; Carrieri, Patrizia; Camoin-Jau, Laurence; Mege, Jean-Louis; Raoult, Didier

2017-07-01

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been

Antibody induction versus placebo, no induction, or another type of antibody induction for liver transplant recipients

DEFF Research Database (Denmark)

Penninga, Luit; Wettergren, André; Wilson, Colin H

2014-01-01

. All 19 trials were with high risk of bias. Of the 19 trials, 16 trials were two-arm trials, and three trials were three-arm trials. Hence, we found 25 trial comparisons with antibody induction agents: interleukin-2 receptor antagonist (IL-2 RA) versus no induction (10 trials with 1454 participants....... Furthermore, serum creatinine was statistically significantly higher when T-cell specific antibody induction was compared with no induction (MD 3.77 μmol/L, 95% CI 0.33 to 7.21; low-quality evidence), as well as when polyclonal T-cell specific antibody induction was compared with no induction, but this small...... T-cell specific antibody induction, drug-related adverse events were less common among participants treated with interleukin-2 receptor antagonists (RR 0.23, 95% CI 0.09 to 0.63; low-quality evidence), but this was caused by the results from one trial, and trial sequential analysis could not exclude...

Probing cocaine-antibody interactions in buffer and human serum.

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Muthu Ramakrishnan

Full Text Available Despite progress in cocaine immunotherapy, the kinetic and thermodynamic properties of antibodies which bind to cocaine and its metabolites are not well understood. It is also not clear how the interactions between them differ in a complex matrix such as the serum present in the human body. In the present study, we have used microscale thermophoresis (MST, isothermal titration calorimetry (ITC, and surface plasmon resonance (SPR we have evaluated the affinity properties of a representative mouse monoclonal (mAb08 as well as those of polyclonal antibodies purified from vaccinated mouse and human patient serum.MST analysis of fluorescently tagged mAb08 binding to cocaine reveals an approximately 15 fold decrease in its equilibrium dissociation constant in 20-50% human serum compared with that in saline buffer. A similar trend was also found using enriched polyclonal antibodies purified from vaccinated mice and patient serum, for which we have used fluorescently tagged bovine serum albumin conjugated to succinyl norcocaine (BSA-SNC. This conjugate closely mimics both cocaine and the hapten used to raise these antibodies. The ITC data also revealed that cocaine has a moderate affinity of about 2 µM to 20% human serum and very little interaction with human serum albumin or nonspecific human IgG at that concentration range. In a SPR inhibition experiment, the binding of mAb08 to immobilized BSA-SNC was inhibited by cocaine and benzoylecgonine in a highly competitive manner, whereas the purified polyclonal antibodies from vaccinated humans and mice, revealed preferential selectivity to pharmacologically active cocaine but not to the inactive metabolite benzoylecgonine. We have also developed a simple binding model to simulate the challenges associated with cocaine immunotherapy using the variable quantitative and kinetic properties of the antibodies.High sensitivity calorimetric determination of antibody binding to cocaine and its metabolites provide

Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

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Waldmann, Herman

2014-01-01

One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.

Recent advances in anti-neutrophil cytoplasmic antibody-associated vasculitis

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B Lazarus

2016-01-01

Full Text Available Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon inflammatory disease of small to medium-sized vessels that frequently presents with rapidly progressive glomerulonephritis and renal failure though it can affect any organ system. If untreated, the vast majority of patients will die within a year. Current treatments improve prognosis but affected patients remain at a substantially higher risk of death and adverse outcomes. We review the classification of the disease, our understanding of the pathogenesis and epidemiology, and propose future directions for research. We also evaluate the evidence supporting established treatment regimens and the progress of clinical trials for newer treatments to inform the design of future studies.

Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

International Nuclear Information System (INIS)

Soos, M.; Siddle, K.

1982-01-01

Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG 1 subclass. Affinities of antibodies for TSH were in the range 2 x 10 8 -5 x 10 10 M -1 . Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

Microbials for the production of monoclonal antibodies and antibody fragments.

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Spadiut, Oliver; Capone, Simona; Krainer, Florian; Glieder, Anton; Herwig, Christoph

2014-01-01

Monoclonal antibodies (mAbs) and antibody fragments represent the most important biopharmaceutical products today. Because full length antibodies are glycosylated, mammalian cells, which allow human-like N-glycosylation, are currently used for their production. However, mammalian cells have several drawbacks when it comes to bioprocessing and scale-up, resulting in long processing times and elevated costs. By contrast, antibody fragments, that are not glycosylated but still exhibit antigen binding properties, can be produced in microbial organisms, which are easy to manipulate and cultivate. In this review, we summarize recent advances in the expression systems, strain engineering, and production processes for the three main microbials used in antibody and antibody fragment production, namely Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli. Copyright © 2013 Elsevier Ltd. All rights reserved.

Taking stock of Myanmar's progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead.

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Saw, Yu Mon; Win, Khine Lae; Shiao, Laura Wen-Shuan; Thandar, Moe Moe; Amiya, Rachel M; Shibanuma, Akira; Tun, Soe; Jimba, Masamine

2013-09-11

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar's progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar's government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar's government should invest greater efforts into health system strengthening to pave the road to universal health coverage.

Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies.

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Ahmed, Yousuf; Tian, Meijuan; Gao, Yong

2017-09-12

The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis

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Staffan Görander

2014-11-01

Full Text Available We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2 of herpes simplex virus 2 (HSV-2 in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1 and IgG2 antibodies were detected and re-stimulated splenic CD4+ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC and complement-mediated cytolysis (ACMC activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.

Antibody Characterization Lab | Office of Cancer Clinical Proteomics Research

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The Antibody Characterization Lab (ACL), an intramural reference laboratory located at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, thoroughly characterizes monoclonal antibodies or other renewable affinity binding reagents for use in cancer related research.

Sex Differences in Time to Return-to-Play Progression After Sport-Related Concussion.

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Stone, Sarah; Lee, Bobby; Garrison, J Craig; Blueitt, Damond; Creed, Kalyssa

2016-10-03

Recently, female sports participation has increased, and there is a tendency for women to experience more symptoms and variable presentation after sport-related concussion (SRC). The purpose of this study was to determine whether sex differences exist in time to begin a return-to-play (RTP) progression after an initial SRC. After initial SRC, female athletes (11-20 years old) would take longer to begin an RTP progression compared with age-matched male athletes. Retrospective cohort study. Level 3. A total of 579 participants (365 males [mean age, 15.0 ± 1.7 years], 214 females [mean age, 15.2 ± 1.5 years]), including middle school, high school, and collegiate athletes who participated in various sports and experienced an initial SRC were included and underwent retrospective chart review. The following information was collected: sex, age at injury, sport, history of prior concussion, date of injury, and date of initiation of RTP progression. Participants with a history of more than 1 concussion or injury sustained from non-sport-related activity were excluded. Despite American football having the greatest percentage (49.2%) of sport participation, female athletes took significantly longer to start an RTP progression after an initial SRC (29.1 ± 26.3 days) compared with age-matched male athletes (22.7 ± 18.3 days; P = 0.002). On average, female athletes took approximately 6 days longer to begin an RTP progression compared with age-matched male athletes. This suggests that sex differences exist between athletes, ages 11 to 20 years, with regard to initiation of an RTP progression after SRC. Female athletes may take longer to recover after an SRC, and therefore, may take longer to return to sport. Sex should be considered as part of the clinical decision-making process when determining plan of care for this population. © 2016 The Author(s).

Exploration of novel strategies to enhance monoclonal antibodies targeting

International Nuclear Information System (INIS)

Khawli, L.A.; Epstein, A.L.

1997-01-01

This paper highlights the major obstacles and prospects of antibody targeting for the radio imaging and therapy of human malignant lymphomas and more challenging solid tumors. To improve the therapeutic potential of monoclonal antibodies, the authors have focused their attention on the development of new and successful methods to augment antibody uptake in the tumor. These approaches include the use of radiolabeled streptavidin to target biotinylated monoclonal antibodies already bound to tumor, pretreatment with vasoactive immunoconjugates, and the use of chemically modified antibodies. Because of the promising preclinical data obtained with these three newer approaches, plans are underway to test them in the clinic. More generally, these approaches are applicable to the use of other monoclonal antibody/tumor systems for the diagnosis and therapy of human cancers and related diseases

Research progress on related genes for primary open angle glaucoma

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Ailijiang·Aierken

2014-04-01

Full Text Available Primary open angle glaucoma(POAGis the main cause of blindness with visual field damage and optic nerve degeneration. In recent years, a lot of researches have been done, showing that genetic factors and gene mutation play an important role in POAG. There are more than 20 related POAG genes. Now we will review the related genes of POAG, especially the well known causative genes of MYOC, OPTN, WDR36, and CAV1/CAV2, in terms of their locations, structures, research progress, et al, and provide a reference for genetic research in primary open-angle glaucoma.

ECT with /sup 123/I-labeled fragments of anti-CEA monoclonal antibodies in colo-rectal cancer

International Nuclear Information System (INIS)

Bischof-Delaloye, A.; Delaloye, B.

1986-01-01

The recent progress of tumor localization with labelled antibodies can be attributed to three techniques: 1) use of I-123 as a label; 2) fragmentation of antibodies; 3) tomographic recording and evaluation of patient radiation data. Under these conditions the method yields good sensitivity and specifity indexes (15/16 for primary tumors and local recurrences, 7/10 for metastasis). A strictly prospective study, however, remains mandatory in order to assess the clinical value of this method

The target invites a foe: antibody-drug conjugates in gynecologic oncology.

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Campos, Maira P; Konecny, Gottfried E

2018-02-01

Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Antibody-drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents. A better and quicker translation of recent scientific advances in the field of ADCs into rational clinical trials for patients diagnosed with ovarian, endometrial or cervical cancer could create real improvements in tumor response, survival and quality of life for our patients.

Experimental tests of general relativity: recent progress and future directions

International Nuclear Information System (INIS)

Turyshev, S G

2009-01-01

Einstein's general theory of relativity is the standard theory of gravity, especially where the needs of astronomy, astrophysics, cosmology, and fundamental physics are concerned. As such, this theory is used for many practical purposes involving spacecraft navigation, geodesy, and time transfer. We review the foundations of general relativity, discuss recent progress in tests of relativistic gravity, and present motivations for the new generation of high-accuracy tests of new physics beyond general relativity. Space-based experiments in fundamental physics are presently capable of uniquely addressing important questions related to the fundamental laws of nature. We discuss the advances in our understanding of fundamental physics that are anticipated in the near future and evaluate the discovery potential of a number of recently proposed space-based gravitational experiments. (reviews of topical problems)

Monoclonal antibody

International Nuclear Information System (INIS)

Oyamada, Hiyoshimaru

1987-01-01

Some aspects of monoclonal antibodies are described, centering on studies made by the author and those presented at the Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer held in March this year (1987). The history of immuno-nuclear medicine and procedures for producing monoclonal antibodies are briefly outlined. Monoclonal antibodies are immunoglobulins. Here, the structure of IgG, which is used most frequently, is described. An IgG is composed of two antigen binding fragments (Fab) and one crystallizable fragment (Fc). The end portion of a Fab reacts with an antigen. One of the major applications of immuno-nuclear medicine is the diagnosis of cancer. As label nucleides, 131 I and 111 I were selected in most cases in the past while 123 I and 99m Tc are currently used more often. Advantages and disadvantages of this diagnosis method is discussed citing studies presented at the First (1986) and Second (1987) International Conference on Monoclonal Antibody Immunoconjugates for Cancer. The present status of the application of monoclonal antibodies to treatment of cancer is also described. (Nogami, K.)

Chimeric recombinant antibody fragments in cardiac troponin I immunoassay.

Science.gov (United States)

Hyytiä, Heidi; Heikkilä, Taina; Brockmann, Eeva-Christine; Kekki, Henna; Hedberg, Pirjo; Puolakanaho, Tarja; Lövgren, Timo; Pettersson, Kim

2015-03-01

To introduce a novel nanoparticle-based immunoassay for cardiac troponin I (cTnI) utilizing chimeric antibody fragments and to demonstrate that removal of antibody Fc-part and antibody chimerization decrease matrix related interferences. A sandwich-type immunoassay for cTnI based on recombinant chimeric (mouse variable/human constant) antigen binding (cFab) antibodies and intrinsically fluorescent nanoparticles was developed. To test whether using chimeric antibody fragments helps to avoid matrix related interferences, samples (n=39) with known amounts of triglycerides, bilirubin, rheumatoid factor (RF) or human anti-mouse antibodies (HAMAs) were measured with the novel assay, along with a previously published nanoparticle-based research assay with the same antibody epitopes. The limit of detection (LoD) was 3.30ng/L. Within-laboratory precision for 29ng/L and 2819ng/L cTnI were 13.7% and 15.9%, respectively. Regression analysis with Siemens ADVIA Centaur® yielded a slope (95% confidence intervals) of 0.18 (0.17-1.19) and a y-intercept of 1.94 (-1.28-3.91) ng/L. When compared to a previously published nanoparticle-based assay, the novel assay showed substantially reduced interference in the tested interference prone samples, 15.4 vs. 51.3%. A rheumatoid factor containing sample was decreased from 241ng/L to related interferences, thus resulting in a lower number of falsely elevated cTnI-values. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Immunotherapy with GD2 specific monoclonal antibodies

International Nuclear Information System (INIS)

Cheung, N.K.V.; Medof, E.M.; Munn, D.

1988-01-01

Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

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Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

Science.gov (United States)

Lim, Theam Soon; Chan, Soo Khim

2016-01-01

Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Final Progress Report: SPECT Assay of Radiolabeled Monoclonal Antibodies

International Nuclear Information System (INIS)

Jaszczak, Ronald J.

2004-01-01

During the past project period, we proposed to collaborate closely with DOE's Thomas Jefferson National Accelerator Facility (Jefferson Lab or JLab) to design a compact, ultra-high-resolution, high-sensitivity gamma camera for quantifying brain-tumor distributions of I-131. We also proposed to continue our on-going research in developing and evaluating pinhole collimation for quantitative ultra-high-resolution imaging of I-131-labeled MAbs. We have made excellent progress in accomplishing much of the research related to pinhole collimation. Many of the most significant results have been presented in peer-reviewed journal articles and conference proceedings. We have also made good progress in collaborating with JLab's Detector Group in developing a compact, ultra-high-resolution, gamma camera. A prototype I-131 imager was delivered to Duke on May 28, 2003. Our research results are summarized in the following sections. A. JLAB-DUKE DEDICATED BRAIN-TUMOR IMAGING SYSTEM A.1. Determination of Optimal Collimator Design During the current project period a prototype I-131 dedicated brain imager has been designed and built. Computer simulations and analysis of alternate designs were performed at Duke to determine an optimal collimator design. Collimator response was characterized by spatial resolution and sensitivity. Both geometric (non-penetrative) and penetrative sensitivities were considered in selecting an optimal collimator design. Based on these simulation results, two collimator designs were selected and built by external vendors. Initial imaging results were obtained using these collimators. B. INITIAL DEVELOPMENT OF SPECT RECONSTRUCTION SOFTWARE FOR JLAB-DUKE CAMERA B.1. Modeling Thick Septa and Collimator Holes: Geometrical-Phantom Study A geometrical phantom was designed to illuminate spatial resolution effects. The phantom includes a uniformly attenuating medium that consists of all voxels within an elliptical cylinder that is centered on the axis of rotation

Human antibody responses to Schistosoma mansoni: does antigen directed, isotype restriction result in the production of blocking antibodies?

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David W. Dunne

1987-01-01

Full Text Available After treatment young Kenyan schoolchildren are highly susceptible to reinfection with Schistosoma mansoni. Older children and adults are resistant to reinfection. There is no evidence that this age related resistance is due to a slow development of protective immunological mechanisms, rather, it appears that young children are susceptible because of the presence of blocking antibodies which decline with age, thus allowing the expression of protective responses. Correlations between antibody responses to different stages of the parasite life-cycle suggest that, in young children, antigen directed, isotype restriction of the response against cross-reactive polysaccharide egg antigens results in an ineffectual, or even blocking antibody response to the schistosomulum.

Detection of HBs antigens and antibodies by immunoenzymology and radioimmunology. Comparison of the results

International Nuclear Information System (INIS)

Fauchet, R.; Genetet, B.; Phengsavath

1981-01-01

The respective sensitivity threshold of immunoenzymology and radioimmunology in HBs antigen and antibody detection were compared and the optical density (o.d.) and counts per minute (cpm) values were correlated with the concentration in ng/ml of a given sample. The sensitivity comparison between RIA and EIA appears in favour of the former technique for both HBs antigen and HBs antibody detection. However the procedure tried here to detect HBs antibodies by immunoenzymology is simple, requires only the choice of neutralising antigenic pool and sensitivity threshold and could usefully be generalized for teams not authorized to handle radioelements. Quantification of the HBs antigen content in ng/ml is a difficult operation, needing great care in the dilution of the sera tested. The reproducibility is not perfect. The semi-quantitative RIA determination expressed in R.U. (radioimmunological units) seems adequate as a mean to follow the progress of an HBs antibody in both liver disease and vaccination [fr

Development and characterization of human monoclonal antibodies that neutralize multiple TGFβ isoforms.

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Bedinger, Daniel; Lao, Llewelyn; Khan, Shireen; Lee, Steve; Takeuchi, Toshihiko; Mirza, Amer M

2016-01-01

Transforming growth factor (TGF)β levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFβ1, 2, and 3. As multiple TGFβ isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFβ isoforms. Fully human antibody phage display libraries were used to discover a number of antibodies that bind and neutralize various combinations of TGFβ1, 2 or 3. The primary panning did not yield any uniformly potent pan-isoform neutralizing antibodies; therefore, an antibody that displayed potent TGFβ 1, 2 inhibition, but more modest affinity versus TGFβ3, was affinity matured by shuffling with a light chain sub-library and further screening. This process yielded a high affinity pan-isoform neutralizing clone. Antibodies were analyzed and compared by binding affinity, as well as receptor and epitope competition by surface plasmon resonance methods. The antibodies were also shown to neutralize TGFβ effects in vitro in 3 assays: 1) interleukin (IL)-4 induced HT-2 cell proliferation; 2) TGFβ-mediated IL-11 release by A549 cells; and 3) decreasing SMAD2 phosphorylation in Detroit 562 cells. The antibodies' potency in these in vitro assays correlated well with their isoform-specific affinities. Furthermore, the ability of the affinity-matured clone to decrease tumor burden in a Detroit 562 xenograft study was superior to that of the parent clone. This affinity-matured antibody acts as a very potent inhibitor of all 3 main isoforms of TGFβ and may have utility for therapeutic intervention in human disease.

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

Science.gov (United States)

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Monoclonal antibodies and cancer

International Nuclear Information System (INIS)

Haisma, H.J.

1987-01-01

The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111 In, 67 Ga and 131 I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

Science.gov (United States)

Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

DARPA Antibody Technology Program. Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody Produced by Illumina

Science.gov (United States)

2016-08-01

ECBC-TR-1395 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR... ANTIBODY CHARACTERIZATION: CHARACTERIZATION OF AN MS2 SCFV ANTIBODY PRODUCED BY ILLUMINA Patricia E. Buckley Alena M. Calm Heather Welsh Roy...4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv

Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

International Nuclear Information System (INIS)

Won, JaeSeon; Nam, PilWon; Lee, YongChan; Choe, MuHyeon

2009-01-01

Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G 4 S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38] 2 ) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

Antiparietal cell antibody test

Science.gov (United States)

APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

Quantitation of antibodies to nucleoribonucleoprotein by ELISA : relation between antibody levels and disease activity in patients with connective tissue disease

NARCIS (Netherlands)

Houtman, PM; Kallenberg, CGM; Limburg, PC; Huitema, MG; van Rijswijk, MH; The, TH

1985-01-01

We describe a solid-phase enzyme-linked immunosorbent assay (ELISA) for quantitation of antibodies to nucleoribonucleoprotein (nRNP/Sm). nRNP/Sm was purified from rabbit thymus acetone powder by immunoaffinity chromatography and characterized by counterimmunoelectrophoresis (CIE) and immunoblotting

Shifts in the Microbial Population in Relation to in situ Caries Progression

NARCIS (Netherlands)

Thomas, R. Z.; Zijnge, V.; Cicek, A.; de Soet, J. J.; Harmsen, H. J. M.; Huysmans, M. C. D. N. J. M.

2012-01-01

The shift in microbial diversity from young to mature plaque, related to caries activity on sound and restored surfaces, was studied using denaturing gradient gel electrophoresis. During a 20-week in situ study on caries progression 8 subjects wearing restored and unrestored dentin and enamel

Shifts in the microbial population in relation to in situ caries progression

NARCIS (Netherlands)

Thomas, R.Z.; Zijnge, V.; Ciçek, A.; de Soet, J.J.; Harmsen, H.J.M.; Huysmans, M.C.D.N.J.M.

2012-01-01

The shift in microbial diversity from young to mature plaque, related to caries activity on sound and restored surfaces, was studied using denaturing gradient gel electrophoresis. During a 20-week in situ study on caries progression 8 subjects wearing restored and unrestored dentin and enamel

Diagnostic significance of DNA and antibodies against capsid antigens of anti-Epstein–Barr virus antibodies levels in blood plasma of nasopharyngeal carcinoma patients from non-endemic region

Directory of Open Access Journals (Sweden)

V. E. Gurtsevich

2015-01-01

Full Text Available Epstein–Barr virus (EBV, a representative of the herpesvirus family, is the etiological agent for a number of benign and malignant human neoplasms. Among the latter, the nasopharyngeal carcinoma (NPC occupies a special place. In NPC development EBV plays a key role stimulating the progression of the pathological process from precancerous lesions to the cancer development. For most NPC patients, elevated levels of humoral IgG and IgA antibodies against capsid and early EBV antigens are characteristic and their antibody titers rise to high levels long before the diagnosis of cancer. Using this phenomenon, virus-specific antibodies are used for many years as markers for NPC screening, especially in cases of undiagnosed primary lesion. In recent years, in endemic for NPC regions (South China, South-East Asia a great attention has been paid to the use of quantitative determination of EBV DNA copies in the blood plasma of patients with NPC as a method of early cancer detection and monitoring.The aim of this study was to compare clinical significance of EBV DNA and humoral antibodies levels in blood plasma of NPC patients in non-endemic region, Russia. The results obtained indicate that both markers DNA / EBV and IgA antibodies against capsid EBV antigens can be successfully used for diagnosis of NPC in non-endemic region. However, in comparison with the virus-specific antibody titers, the viral DNA levels in the patients plasma are more sensitive and specific as NPC marker reflecting the efficacy of the therapy, and the state of remission or relapse.

The state-of-play and future of antibody therapeutics.

Science.gov (United States)

Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

2017-12-01

It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

DEFF Research Database (Denmark)

Lyksborg, Mark; Siebner, Hartwig R.; Sørensen, Per S.

2014-01-01

Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy...

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

Science.gov (United States)

Morozumi, T; Nakagawa, T; Nomura, Y; Sugaya, T; Kawanami, M; Suzuki, F; Takahashi, K; Abe, Y; Sato, S; Makino-Oi, A; Saito, A; Takano, S; Minabe, M; Nakayama, Y; Ogata, Y; Kobayashi, H; Izumi, Y; Sugano, N; Ito, K; Sekino, S; Numabe, Y; Fukaya, C; Yoshinari, N; Fukuda, M; Noguchi, T; Kono, T; Umeda, M; Fujise, O; Nishimura, F; Yoshimura, A; Hara, Y; Nakamura, T; Noguchi, K; Kakuta, E; Hanada, N; Takashiba, S; Yoshie, H

2016-12-01

A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-insulin antibody test

Science.gov (United States)

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka

Directory of Open Access Journals (Sweden)

S. M. K. Gamage

2018-01-01

Full Text Available Multiple sclerosis (MS is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP results, oligoclonal bands (OCB, and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients.

Science.gov (United States)

Petricevic, Branka; Laengle, Johannes; Singer, Josef; Sachet, Monika; Fazekas, Judit; Steger, Guenther; Bartsch, Rupert; Jensen-Jarolim, Erika; Bergmann, Michael

2013-12-12

Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to

Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

Directory of Open Access Journals (Sweden)

Pei Xuan Lee

2016-06-01

Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

Science.gov (United States)

Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

2016-06-01

Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

Science.gov (United States)

Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

2016-01-01

Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

Hepatitis A virus antibody

International Nuclear Information System (INIS)

Novak, J.; Kselikova, M.; Urbankova, J.

1980-01-01

A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125 I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

Muller cell-specific autoantibodies in a patient with progressive loss of vision

NARCIS (Netherlands)

Peek, R.; Verbraak, F.; Coevoet, H. M.; Kijlstra, A.

1998-01-01

PURPOSE. To study the specificity of circulating retinal autoantibodies in a patient with progressive loss of vision resembling cancer-associated retinopathy in the absence of systemic malignancy. METHODS. Patient's serum was tested for the presence of antiretinal antibodies by Western blot

Voltage-Gated Potassium Channel Antibody Paraneoplastic Limbic Encephalitis Associated with Acute Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Marion Alcantara

2013-05-01

Full Text Available Among paraneoplastic syndromes (PNS associated with malignant hemopathies, there are few reports of PNS of the central nervous system and most of them are associated with lymphomas. Limbic encephalitis is a rare neurological syndrome classically diagnosed in the context of PNS. We report the case of a 81-year-old man who presented with a relapsed acute myeloid leukemia (AML with minimal maturation. He was admitted for confusion with unfavorable evolution as he presented a rapidly progressive dementia resulting in death. A brain magnetic resonance imaging, performed 2 months after the onset, was considered normal. An electroencephalogram showed non-specific bilateral slow waves. We received the results of the blood screening of neuronal autoantibodies after the patient's death and detected the presence of anti-voltage-gated potassium channel (VGKC antibodies at 102 pmol/l (normal at <30 pmol/l. Other etiologic studies, including the screening for another cause of rapidly progressive dementia, were negative. To our knowledge, this is the first case of anti-VGKC paraneoplastic limbic encephalitis related to AML.

Nuclear medicine: Monoclonal antibodies

International Nuclear Information System (INIS)

Endo, K.; Sakahara, H.; Koizumi, M.; Kawamura, Y.; Torizuka, K.; Yokoyama, A.

1986-01-01

Antitumor monoclonal antibody was successfully labeled with Tc-99m by using dithiosemicarbazone (DTS) as a bifunctional chelating agent. In the first step, DTS was coupled to antibody without loss of immunoreactivity; the compound then efficiently formed a neutral 1:1 chelate with pentavalent or tetravalent Tc-99m. Imaging with Tc-99m-labeled monoclonal antibody to human osteosarcoma (OST-7) clearly displayed a small tumor in nude mice at 6 and 24 hours after intravenous administration. The tumor-to-blood ratio of the Tc-99m-labeled monoclonal antibody was higher than that of a radioiodinated antibody and similar to that of an In-111-labeled antibody. Thus, conjugation of DTS to monoclonal antibody followed by radiometalation is a simple and efficient method of preparing Tc-99m-labeled monoclonal antibody

Maternally transmitted antibodies to pregnancy-associated variant antigens on the surface of erythrocytes infected with Plasmodium falciparum: relation to child susceptibility to malaria

DEFF Research Database (Denmark)

Cot, Michel; Le Hesran, Jean Yves; Staalsoe, Trine

2003-01-01

The consequences of pregnancy-associated malaria on a child's health have been poorly investigated. Malarial infection of the placenta seems to result in a higher susceptibility of children to the parasite during their first year of life. In 1993-1995, the authors investigated the role of antibod......The consequences of pregnancy-associated malaria on a child's health have been poorly investigated. Malarial infection of the placenta seems to result in a higher susceptibility of children to the parasite during their first year of life. In 1993-1995, the authors investigated the role......, Cameroon. These newborns were subsequently followed up for 2 years to determine the date of first occurrence of blood parasites and mean parasite density during follow-up. Maternally transmitted antibodies to VSA expressed by CSA-binding parasites, but not antibodies to any other specificity, were...... negatively related to time of first appearance of Plasmodium falciparum in a child's blood and were positively related to mean parasite density during the first 2 years of life. If maternal infection is thought to be the main mechanism influencing susceptibility of the newborn to malaria, antibodies to VSA...

Anti-Ma2/Ta antibodies in a woman with primary lateral sclerosis-like phenotype and Sjögren syndrome.

Science.gov (United States)

Piccolo, Giovanni; Tavazzi, Eleonora; Jarius, Sven; Alfonsi, Enrico; Cavagna, Lorenzo; Piccolo, Laura; Zardini, Elisabetta; Voltz, Raymond; Franciotta, Diego

2011-10-01

Anti-Ma2/Ta antibodies are rare paraneoplastic antibodies, which are mostly associated with limbic encephalitis in male patients with testicular cancer. We report on a 50-year-old woman with a pure progressive spastic paraparesis. Next, she was diagnosed as having a Sjögren syndrome, with serological positivity for anti-SS-Ro antibodies. The patient's serum and cerebrospinal fluid samples were positive for anti-Ma2/Ta antibodies, which were also proved to be intrathecally produced. These findings, and the coexistence of systemic autoimmunity, led us to treat the patient with corticosteroids first, and then with plasma exchange. Neurological symptoms scarcely responded to both the therapies. The search for cancer was negative up to 4 years after the disease onset. Our case expands the spectrum of clinical syndromes associated with anti-Ma2/Ta antibodies.

[Progress of midfacial fat compartments and related clinical applications].

Science.gov (United States)

Wen, Lihong; Wang, Jinhuang; Li, Yang; Liu, Dalie

2018-02-01

To review the research progress of midfacial fat compartments, and to thoroughly understand its current state of the anatomy and the aging morphologic characters of midfacial fat compartments, as well as the current status of clinical applications. The recent literature concerning the midfacial fat compartments and related clinical applications were extensively reviewed and analyzed. Midfacial fat layer has been considered as a fusion and a continuous layer, experiencing a global atrophy when aging. As more anatomical researches have done, recent studies have shown that midfacial fat layer is broadly divided into superficial and deep layers, which are both divided into different fat compartments by fascia, ligaments, or muscles. Midfacial fat compartments tend to atrophy with age, specifically in the deep fat compartments while hypertrophy in the superficial fat compartments. Clinical applications show that fat volumetric restoration with deep medial cheek fat and Ristow's space can restore the appearance of midface effectively. In recent years, the researches of midfacial fat compartments have achieved obvious progress, which will provide new ideas and basis for fat volumetric restoration. Corresponding treatments are selected based on different sites and different layers with different aging changes, reshaping a more youthful midface.

Is there a role for antibody testing in the diagnosis of invasive candidiasis?

Science.gov (United States)

Quindós, Guillermo; Moragues, María Dolores; Pontón, José

2004-03-01

During the last decades, the use of antibody tests for the diagnosis of invasive mycoses has declined as a consequence of the general belief that they are insensitive and non-specific. However, there is a clear evidence that antibodies can be detected in highly immunodeficient patients (such as bone marrow transplant recipients), and that those antibodies are useful for the diagnosis. Antibody tests are currently in use as diagnostic tools for some primary mycoses, such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis and sporothrichosis. For invasive candidiasis, diagnostic methods must differentiate Candida colonization of mucous membranes or superficial infection from tissue invasion by this microorganism. Substantial progress has been made in diagnosis of invasive candidiasis with the development of a variety of methods for the detection of antibodies and antigens. However, no single test has found widespread clinical use and there is a consensus that diagnosis based on a single specimen lacks sensitivity. It is necessary to test sequential samples taken while the patient is at greatest risk for developing invasive candidiasis to optimize the diagnosis. Results obtained from a panel of diagnostic tests in association with clinical aspects will likely be the most useful strategy for early diagnosis and therapy.

Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators.

Science.gov (United States)

Luh, Jeanne; Bartram, Jamie

2016-02-01

To assess progress in the provision of drinking water and sanitation in relation to national socioeconomic indicators. We used household survey data for 73 countries - collected between 2000 and 2012 - to calculate linear rates of change in population access to improved drinking water (n = 67) and/or sanitation (n = 61). To enable comparison of progress between countries with different initial levels of access, the calculated rates of change were normalized to fall between -1 and 1. In regression analyses, we investigated associations between the normalized rates of change in population access and national socioeconomic indicators: gross national income per capita, government effectiveness, official development assistance, freshwater resources, education, poverty, Gini coefficient, child mortality and the human development index. The normalized rates of change indicated that most of the investigated countries were making progress towards achieving universal access to improved drinking water and sanitation. However, only about a third showed a level of progress that was at least half the maximum achievable level. The normalized rates of change did not appear to be correlated with any of the national indicators that we investigated. In many countries, the progress being made towards universal access to improved drinking water and sanitation is falling well short of the maximum achievable level. Progress does not appear to be correlated with a country's social and economic characteristics. The between-country variations observed in such progress may be linked to variations in government policies and in the institutional commitment and capacity needed to execute such policies effectively.

Coaches' Coaching Competence in Relation to Athletes' Perceived Progress in Elite Sport

Science.gov (United States)

Moen, Frode; Federici, Roger A.

2013-01-01

This article looks at whether higher levels of perceived coaching competencies focusing on relational issues, were associated with higher satisfaction among elite athletes with their progress in sport. In order to explore this, we investigated elite athletes' perceptions of their coaches' coaching competence (CCS) and how these perceptions related…

Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

Science.gov (United States)

Chuerduangphui, Jureeporn; Pientong, Chamsai; Swangphon, Piyawut; Luanratanakorn, Sanguanchoke; Sangkomkamhang, Ussanee; Tungsiriwattana, Thumwadee; Kleebkaow, Pilaiwan; Burassakarn, Ati; Ekalaksananan, Tipaya

2018-05-09

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16 INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16 INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16 INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16 INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16 INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16 INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

Current status of radioligand antibodies in the treatment of malignancy

International Nuclear Information System (INIS)

Maners, A.W.; Sanders, M.M.; Pappas, A.A.

1988-01-01

Monoclonal anti-tumor antibodies labeled with a radioactive moiety present an exciting new approach to cancer therapy. With the advent of hybridoma technology, monoclonal antibodies can now be produced in quantity. Indeed, antibodies against tumor-related and tumor-specific antigens have been produced, labeled with a radioactive substance, and used therapeutically. The rationale for this therapeutic approach and the results of human clinical trials will be reported herein.27 references

Baculovirus display of functional antibody Fab fragments.

Science.gov (United States)

Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

2015-08-01

The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

Science.gov (United States)

Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-07-05

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

Science.gov (United States)

Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-01-01

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

International Nuclear Information System (INIS)

Glaessner, H.

1986-01-01

The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab') 2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV) [de

Specificity and polyreactivity of the antibody response during natural HIV-1 infection

OpenAIRE

Wang, Xin

2006-01-01

The specificity and polyreactivity of the antibody response in natural HIV-1 infection were studied. First, to investigate the overall antibody response, overlapping linear peptides were used to screen sera taken from HIV-1-infected individuals. The polyclonal antibody response was relatively stable during long-term infection, compared with acute infection, and mostly directed against immunodominant regions. Low level, transient antibody responses were detected against membrane proximal exter...

Kotai Antibody Builder: automated high-resolution structural modeling of antibodies.

Science.gov (United States)

Yamashita, Kazuo; Ikeda, Kazuyoshi; Amada, Karlou; Liang, Shide; Tsuchiya, Yuko; Nakamura, Haruki; Shirai, Hiroki; Standley, Daron M

2014-11-15

Kotai Antibody Builder is a Web service for tertiary structural modeling of antibody variable regions. It consists of three main steps: hybrid template selection by sequence alignment and canonical rules, 3D rendering of alignments and CDR-H3 loop modeling. For the last step, in addition to rule-based heuristics used to build the initial model, a refinement option is available that uses fragment assembly followed by knowledge-based scoring. Using targets from the Second Antibody Modeling Assessment, we demonstrate that Kotai Antibody Builder generates models with an overall accuracy equal to that of the best-performing semi-automated predictors using expert knowledge. Kotai Antibody Builder is available at http://kotaiab.org standley@ifrec.osaka-u.ac.jp. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Anti-FGF23 antibody therapy for patients with tumor-induced osteomalacia].

Science.gov (United States)

Kinoshita, Yuka; Fukumoto, Seiji

2014-08-01

Tumor-induced osteomalacia (TIO) is a disease caused by fibroblast growth factor 23 (FGF23) secreted from the causative tumor. This disease is cured by complete surgical removal of the tumor. However, there are several difficult cases in which the responsible tumors cannot be found, are incompletely removed, or relapse after the surgery. Anti-FGF23 antibody is being studied as a novel therapy for FGF23-related hypophosphatemic diseases. The efficacy of anti-FGF23 antibodies were confirmed using a murine model of X-linked hypophosphatemic rickets (XLHR) , which is the most common heritable form of FGF23-related hypophosphatemic disease. In addition, results of phase I study of single injection of humanized anti-FGF23 antibody for adult patients with XLHR were recently published and the safety and effectiveness of this antibody was shown. This antibody therapy may be useful for patients with TIO with similar pathogenesis to that of XLHR.

Thyroid-stimulating hormone, anti-thyroid antibodies, and pregnancy outcomes.

Science.gov (United States)

Plowden, Torie C; Schisterman, Enrique F; Sjaarda, Lindsey A; Perkins, Neil J; Silver, Robert; Radin, Rose; Kim, Keewan; Galai, Noya; DeCherney, Alan H; Mumford, Sunni L

2017-12-01

Overt thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications. The purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia. We conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index. Among women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ≤2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies. Among women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current

Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

International Nuclear Information System (INIS)

Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

2014-01-01

There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

Energy Technology Data Exchange (ETDEWEB)

Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

2014-09-10

There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

Carotid artery disease progression and related neurologic events after carotid endarterectomy.

Science.gov (United States)

Avgerinos, Efthymios D; Go, Catherine; Ling, Jennifer; Naddaf, Abdallah; Steinmetz, Amy; Abou Ali, Adham N; Makaroun, Michel S; Chaer, Rabih A

2016-08-01

glomerular filtration rate (GFR) of 30 to 59 vs <30 mL/min/1.73 m 2 (HR, 0.34; P = .009) or GFR ≥60 vs GFR <30 mL/min/1.73 m 2 (HR, 0.55; P = .109), and statin use (HR, 0.59; P = .006). Restenosis or contralateral disease progression after CEA, to a level that might warrant consideration for treatment, is very low. The potentially associated stroke rates are also very low and not clearly related to disease progression. With the exception of the postoperative duplex, surveillance within short intervals of <1 or 2 years cannot be justified. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

ELISA to measure neutralizing capacity of anti-C1-inhibitor antibodies in plasma of angioedema patients

NARCIS (Netherlands)

Engel, Ruchira; Rensink, Irma; Roem, Dorina; Brouwer, Mieke; Kalei, Asma; Perry, Dawn; Zeerleder, Sacha; Wouters, Diana; Hamann, Dörte

2015-01-01

Neutralizing autoantibodies (NAbs) against plasma serpin C1-inhibitor (C1-inh) are implicated in the rare disorder, acquired angioedema (AAE). There is insufficient understanding of the process of antibody formation and its correlation with disease progression and severity. We have developed an

[Limbic encephalitis with antibodies against intracellular antigens].

Science.gov (United States)

Morita, Akihiko; Kamei, Satoshi

2010-04-01

Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

Taking stock of Myanmar’s progress toward the health-related Millennium Development Goals: current roadblocks, paths ahead

Science.gov (United States)

2013-01-01

Myanmar is a developing country with considerable humanitarian needs, rendering its pursuit of the Millennium Development Goals (MDGs) an especially high priority. Yet progress to date remains under-examined on key fronts. Particularly within the three health-related MDGs (MDGs 4, 5, and 6), the limited data reported point to patchy levels of achievement. This study was undertaken to provide an overview and assessment of Myanmar’s progress toward the health-related MDGs, along with possible solutions for accelerating health-related development into 2015 and beyond. The review highlights off-track progress in the spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar’s achievements toward MDG 6 targets – in the areas of HIV/AIDS, malaria, and tuberculosis. Such achievements are especially notable in that Myanmar has been receiving the lowest level of official development assistance among all of the least developed countries in Asia. However, to make similar progress in MDGs 4 and 5, Myanmar needs increased investment and commitment in health. Toward moving forward with the post-2015 development agenda, Myanmar’s government also needs to take the lead in calling for attention from the World Health Organization and its global development partners to address the stagnation in health-related development progress within the country. In particular, Myanmar’s government should invest greater efforts into health system strengthening to pave the road to universal health coverage. PMID:24025845

Thyroid stimulating antibodies, thyroglobulin antibodies and serum proteins during treatment of graves' disease with radioiodine or propylthouracil

Energy Technology Data Exchange (ETDEWEB)

Feldt-Rasmussen, U; Bech, K; Johansen, K; Nistrup Madsen, S [Dept. of Internal Medicine and Endocrinology F, Herlev University Hospital, Copenhagen (Denmark); Date, J; Hyltoft Pedersen, P [Dept. of Clinical Chemistry, Odense University Hospital, (Denmark)

1982-01-01

The relation between serum concentrations of thyroglobulin antibodies (TgAb), thyroid stimulating antibodies (TSAb) and serum immunoglobulins during treatment of Graves disease was studied in 36 consecutive patients treated randomly with 131-iodine (n=16) or propylthiouracil (n=20). The patients were investigated before treatment was started and on seven occasions within the following year. In the entire patient group 78% were positive for TSAb and 47% for TgAb. There was a significant correlation between TSAb and TgAb in 15 patients concomitantly positive. There were no significant changes in serum immunoglobulins during treatment in either group of patients. In the radioiodine-treated group of patients TgAb was reduced after one week, whereas TSAb showed insignificant variations. After 5-10 weeks both antibodies increased, for TgAb with a median peak level 3 times above the initial concentration. Of 16 patients treated with radioiodine five developed myxoedema and four of these were positive for TgAb. There was a relation between the development of myxoedema and the ratio between increases of TSAb and TgAb. Increase in the TSAb was not related to serum thyroglobulin (Tg) measured in TgAb-negative patients. Propylthiouracil showed minor effects on the studied variables, but with lower mean values of Tg, TgAb and TSAb at the end of the observation period. The results indicate an immunological relation between TSAb and TgAb, although differences between their courses exist in some situations.

Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of neovascular age-related macular degeneration.

Science.gov (United States)

Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

2015-06-01

To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Prospective interventional case series. setting: Clinical practice. Thirty patients (31 eyes) with treatment-naïve neovascular AMD. Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. RPE response, geographic atrophy (GA) progression. Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Monkey-derived monoclonal antibodies against Plasmodium falciparum

International Nuclear Information System (INIS)

Stanley, H.A.; Reese, R.T.

1985-01-01

A system has been developed that allows efficient production of monkey monoclonal antibodies from owl monkeys. Splenocytes or peripheral blood lymphocytes from monkeys immune to the human malarial parasite, Plasmodium falciparum, were fused with P3X63 Ag8.653 mouse myelomas. The resulting hybridomas were screened by an indirect fluorescent antibody test for the production of monkey monoclonal antibodies (mAb) reactive with P. falciparum. Most of the mAb reacted with the P. falciparum merozoites and immunoprecipitated a parasite-derived glycoprotein having a relative molecular weight of 185,000. These mAb gave a minimum of five different immunoprecipitation patterns, thus demonstrating that a large number of polypeptides obtained when parasitized erythrocytes are solubilized share epitopes with this large glycoprotein. In addition, mAb were obtained that reacted with antigens associated with the infected erythrocyte membrane. One of these mAb bound a M/sub r/ 95,000 antigen. Radioimmunoprecipitation assays using 125 T-antibodies were done

Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies.

Science.gov (United States)

Beck, Alain; Reichert, Janice M

2011-01-01

Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.

Next-Generation Sequencing of Antibody Display Repertoires

Directory of Open Access Journals (Sweden)

Romain Rouet

2018-02-01

Full Text Available In vitro selection technology has transformed the development of therapeutic monoclonal antibodies. Using methods such as phage, ribosome, and yeast display, high affinity binders can be selected from diverse repertoires. Here, we review strategies for the next-generation sequencing (NGS of phage- and other antibody-display libraries, as well as NGS platforms and analysis tools. Moreover, we discuss recent examples relating to the use of NGS to assess library diversity, clonal enrichment, and affinity maturation.

Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.

Science.gov (United States)

Jaramillo, A; Smith, M A; Phelan, D; Sundaresan, S; Trulock, E P; Lynch, J P; Cooper, J D; Patterson, G A; Mohanakumar, T

1999-04-27

Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients. Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets. When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (PELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.

Science.gov (United States)

Fuss, Alexander; Hope, Christopher M; Deayton, Susan; Bennett, Greg Donald; Holdsworth, Rhonda; Carroll, Robert P; Coates, P Toby H

2015-07-01

Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure. We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening. All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy. These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers. © 2015 Asian Pacific Society of Nephrology.

The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

Science.gov (United States)

Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

2015-12-01

To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

Science.gov (United States)

Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

2015-01-01

Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

Antibody biotechnology

African Journals Online (AJOL)

STORAGESEVER

2009-07-06

Jul 6, 2009 ... Another milestone in the history of antibodies was the work of Porter and Edelman ... transgenic animals (Lonberg et al., 1994; Green et al.,. 1994) or .... create and to screen human recombinant antibodies libraries, that is ...

[Immunohematologic study and transfusion approach to patients with public antibodies].

Science.gov (United States)

Solves, P; de la Rubia, J; Arriaga, F; Cervera, J; Arnao, M; Carpio, N; Marty, M L

1997-02-01

To analyze the different immunohematologic studies required to identify anti-red cell antibodies directed against high incidence antigens and comment the best tranfusion management. Five patients with suspected anti-red cell alloantibodies directed against high frequency antigens are reported. After a positive antibody screening test (AST), an agglutination test with a commercial panel of 24 red cells was performed. Red cells were treated with proteolytic enzymes and AET to try to identify the circulating antibody. However, it was necessary to send the samples to reference laboratories for definitive identification. In order to evaluate the haemolytic potential of the antibody serum samples were treated with DTT and immunoglobulin subtype was studied with the capillary agglutination test. Finally, we analyze the half life of Cr51 labelled red cells. To obtain compatible blood for transfusion, autologous transfusion and cross-match with blood from direct relatives were performed. AST was positive in every case. A decrease in the agglutination test was observed after ficin treatment in two patients, and an increase in the remaining. The treatment of red cells with ZZAP and AET resulted in a decrease of agglutination in three cases and an increase in the remaining two. Specificity of the antibodies was as follows: anti-Cellano (two cases), anti-Ku (one case) and anti-Yta (two cases). Anti-Kell antibodies were IgG1 and anti-Cartwright antibodies were IgG4. One patient was transfused with autologous blood alone, another patient received compatible blood from direct relatives. A third patient was transfused both with autologous and allogeneic compatible blood. The fourth patient did not need red cell transfusion and, finally the last patient had to be transfused with incompatible blood but no postransfusion haemolysis was observed. In patients with anti-red cell antibodies against high-frequency antigens, red blood cells treatment with proteolytic enzymes (ZZAP, ficin

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children.

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Broliden, K; Sievers, E; Tovo, P A; Moschese, V; Scarlatti, G; Broliden, P A; Fundaro, C; Rossi, P

1993-01-01

The prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression. PMID:8324904

Merkel cell polyomavirus IgG antibody levels are associated with progression to AIDS among HIV-infected individuals.

Science.gov (United States)

Vahabpour, Rouhollah; Nasimi, Maryam; Naderi, Niloofar; Salehi-Vaziri, Mostafa; Mohajel, Nasir; Sadeghi, Farzin; Keyvani, Hossein; Monavari, Seyed Hamidreza

2017-04-01

The association of Merkel cell polyomavirus (MCP y V) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCP y V specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCP y V antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCP y V was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCP y V-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCP y V IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCP y V-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCP y V viral load among the groups ranged between 0.15 to 2.9 copies/10 3 cells (median, 1.9 copies/10 3 cells), with no significant difference between the studied populations (p value = 0.3).

Expression of recombinant Antibodies

Directory of Open Access Journals (Sweden)

André eFrenzel

2013-07-01

Full Text Available Recombinant antibodies are highly specific detection probes in research, diagnostics and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines and transgenic plants are promising to obtain antibodies with human-like post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

Directory of Open Access Journals (Sweden)

Amy E Gilbert

Full Text Available Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10 to primary and metastatic melanoma cells compared to healthy volunteers (n = 10 (P<0.0001. Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21 (P<0.0001. Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800 compared to 2% of cultures from healthy controls (n = 600 produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

Science.gov (United States)

Gilbert, Amy E.; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H.; Takhar, Pooja; Geh, Jenny L. C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Rudman, Sarah M.; Beavil, Rebecca L.; Blower, Philip J.; Beavil, Andrew J.; Gould, Hannah J.; Spicer, James; Nestle, Frank O.; Karagiannis, Sophia N.

2011-01-01

Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer. PMID:21559411

Measles Antibodies in Mother-Infant Dyads in Tianjin, China.

Science.gov (United States)

Boulton, Matthew L; Wang, Xiexiu; Wagner, Abram L; Zhang, Ying; Carlson, Bradley F; Gillespie, Brenda W; Ding, Yaxing

2017-11-27

Many measles cases in Tianjin, China, occur in infants whose mothers were born after widespread vaccination programs. We assessed age-specific decreases in maternal measles antibodies in infants and examined maternal and infant characteristics in relation to infant antibody titers. Infant and mother dyads were enrolled from a sample of immunization clinics in all Tianjin districts. Participants' antibody titers were measured from dried blood spots. A multivariable log-linear model regressed infant antibody titers onto infant and mother characteristics. Among 551 infants aged ≤8 months, protective levels of measles antibodies were observed in infants whose mothers had measles titers ≥800 IU/mL (mean antibody titer, 542.5 IU/mL) or 400 to measles and an accordingly low efficiency of transplacental transmission to a fetus. Current vaccination programs, which target children aged 8 months through adolescence may be ineffective in controlling transmission of measles to infants. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Antiphospholipid syndrome, antiphospholipid antibodies and solid organ transplantation.

Science.gov (United States)

González-Moreno, J; Callejas-Rubio, J L; Ríos-Fernández, R; Ortego-Centeno, N

2015-11-01

Antiphospholipid syndrome is considered a high risk factor for any kind of surgery. Considering that all solid organ transplants are critically dependent on the patency of vascular anastomosis, there is much concern about the consequences this pro-thrombotic condition may have on transplantation. Relatively little information is available in the literature assessing the real risk that antiphospholipid syndrome or the presence of antiphospholipid antibodies represent in solid organ transplantation. The aim of this article is to review the literature related to transplantation of solid organs in patients diagnosed with antiphospholipid syndrome or patients with positive antiphospholipid antibodies. © The Author(s) 2015.

Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies.

Science.gov (United States)

Schroeijers, A B; Scheffer, G L; Reurs, A W; Pijnenborg, A C; Abbondanza, C; Wiemer, E A; Scheper, R J

2001-11-01

The Mr 110,000 lung resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.

Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.

Science.gov (United States)

Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

2017-06-12

The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

T-helper cytokine patterns and related antibodies in patients with gestational diabetes mellitus

Directory of Open Access Journals (Sweden)

Etaati Z

2012-04-01

Conclusion: The changes in T-helper 1 and 2 associated antibodies and cytokines are not associated with gestational diabetes mellitus and could not be considered as a predictor for gestational diabetes mellitus.

Progress of pharmacogenomic research related to minerals and trace elements.

Science.gov (United States)

Zeng, Mei-Zi; Tang, Jie; Liu, Zhao-Qian; Zhou, Hong-Hao; Zhang, Wei

2015-10-01

Pharmacogenomics explores the variations in both the benefits and the adverse effects of a drug among patients in a target population by analyzing genomic profiles of individual patients. Minerals and trace elements, which can be found in human tissues and maintain normal physiological functions, are also in the focus of pharmacogenomic research. Single-nucleotide polymorphisms (SNPs) affect the metabolism, disposition and efficacy of minerals and trace elements in humans, resulting in changes of body function. This review describes some of the recent progress in pharmacogenomic research related to minerals and trace elements.

Bulk tank milk ELISA for detection of antibodies to Mycobacterium avium subsp paratuberculosis: Correlation between repeated tests and within-herd antibody-prevalence

DEFF Research Database (Denmark)

Nielsen, Søren Saxmose; Toft, Nils

2014-01-01

Detection of bulk tank milk (BTM) antibodies using ELISA (BTM-ELISA) may constitute an inexpensive test for surveillance of Mycobacterium avium subsp. paratuberculosis (MAP) infection in dairy cattle herds provided that the test is accurate and consistent. The objectives of this study were...... Danish Holstein herds over a period of one year. All samples were tested using a commercial indirect ELISA for detection of MAP specific antibodies. The individual cow's results were dichotomised and used to estimate the within-herd antibody prevalence at each test-date. These prevalences were...... to 0.60 when corrected for the within-herd antibody prevalence. Although the test-results were relatively consistent and correlated with the within-herd prevalence, the magnitude of the test-values makes it difficult to use the BTM-ELISA for surveillance of MAP infections in practice....

Seroprevalence of Leptospira antibodies among populations at risk

Directory of Open Access Journals (Sweden)

Abdul-Baki Abdullah Al-Robasi

2015-03-01

Full Text Available Objective: This study was performed to assess the Leptospira IgG antibodies seroprevalence among populations at risk in Hodeida Governorate, Yemen. Methods: A total of 200 subjects (136 males and 64 females participated in this study during June and December 2012.They represented 10 sewage workers, 22 butchers, 16 construction workers, 108 agriculture workers, 20 hospital sanitary workers and 24 blood donors. Predesigned questionnaires and consent were taken from each individual. Blood samples were collected from subjects, and the sera were tested by ELISA to detect the presence of leptospira IgG antibodies. The possible related factors for seropositivity were evaluated. Results: Leptospira IgG antibodies were found positive in 42% of the participants. The highest seroprevalence level was detected in sewage workers (80%, followed by hospital sanitary workers (60%, construction workers (37.5% and farmers (37%. The lowest of antibodies was in butchers (36.4%. Seroprevalence among blood donors was 25% which was comparatively less than of the populations at risk. Seropositivity of Leptospira IgG antibodies was found higher among males than females (42.6% vs. 34.4%. The highest Leptospira antibodies seropositivity was among elderly participants (81.8%. The seropositivity of antibodies in population live in rural and urban areas was not significant differences. As for closely contacting with animals, the highest antibodies were discovered in people who had goats (80% and sheep (60.9%. Conclusion: Individuals engaged in risk activities are often exposed to leptospiral infection. Therefore, control and prevention policy toward these people are necessary. J Microbiol Infect Dis 2015;5(1: 1-4

Antibody profiling sensitivity through increased reporter antibody layering

Science.gov (United States)

Apel, William A; Thompson, Vicki S

2013-02-26

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Antibody profiling sensitivity through increased reporter antibody layering

Energy Technology Data Exchange (ETDEWEB)

Apel, William A.; Thompson, Vicki S.

2017-03-28

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Antibody profiling sensitivity through increased reporter antibody layering

Energy Technology Data Exchange (ETDEWEB)

Apel, William A.; Thompson, Vicki S.

2013-02-26

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Antibody profiling sensitivity through increased reporter antibody layering

Energy Technology Data Exchange (ETDEWEB)

Apel, William A.; Thompson, Vicki S

2010-04-13

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Mid-term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes.

Science.gov (United States)

Uno, Kohei; Seki, Yosuke; Kasama, Kazunori; Wakamatsu, Kotaro; Hashimoto, Kenkichi; Umezawa, Akiko; Yanaga, Katsuhiko; Kurokawa, Yoshimochi

2017-12-11

Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin-dependent diabetes mellitus, are limited. We investigated five Japanese patients with slowly progressive insulin-dependent diabetes mellitus who underwent bariatric surgery at our center. Five morbidly obese glutamic acid decarboxylase antibody-positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti-glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m 2 , respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C-peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid-term. Bariatric surgery for morbidly obese patients with anti-glutamic acid decarboxylase antibody-positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid-term glycemic control. Longer follow-up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin-dependent diabetes mellitus, will be needed. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

Science.gov (United States)

Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

2015-01-01

Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract.

Science.gov (United States)

Mathew, Milan C; Ervin, Ann-Margret; Tao, Jeremiah; Davis, Richard M

2012-06-13

Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context. To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials. We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo. Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data were available. We did not perform a sensitivity analysis. Nine trials involving 117

Antisporozoite antibodies in mice immunized with irradiation-attenuated Plasmodium berghei sporozoites

International Nuclear Information System (INIS)

Hansen, R.; Silva, S.de; Strickland, G.T.

1979-01-01

Sera from NMRI/NIH mice were tested for the presence of IgM and IgG anti-sporozoite antibodies using the indirect fluorescent antibody test (IFAT). Both IgM and IgG antibody titres were related to the number of immunizations with irradiation-attenuated Plasmodium berghei sporozoites, and protection from challenge with subsequent non-attenuated sporozoites correlated with the pre-challenge antibody titre. Sera taken five days following challenge showed marked reductions in antibody titres, except for the group receiving the maximum (four) immunizations. Groups immunized with frozen sporozoites or mosquito tissue antigen developed neither antibodies to sporozoites nor protective immunity; nor did animals infected with parasitized blood. However, sera from mice immunized four times with attenuated sporozoites demonstrated IFA titres to blood-stage antigens. The results showed that both IgM and IgG anti-sporozoite antibodies could be detected in mice immunized with attenuated-sporozoites by IFAT, and that the antibody titres correlated with protective immunity. Cross reaction with blood-stage antigens occurred, but the test should still prove useful. (author)

Next-Generation DNA Sequencing of VH/VL Repertoires: A Primer and Guide to Applications in Single-Domain Antibody Discovery.

Science.gov (United States)

Henry, Kevin A

2018-01-01

Immunogenetic analyses of expressed antibody repertoires are becoming increasingly common experimental investigations and are critical to furthering our understanding of autoimmunity, infectious disease, and cancer. Next-generation DNA sequencing (NGS) technologies have now made it possible to interrogate antibody repertoires to unprecedented depths, typically by sequencing of cDNAs encoding immunoglobulin variable domains. In this chapter, we describe simple, fast, and reliable methods for producing and sequencing multiplex PCR amplicons derived from the variable regions (V H , V H H or V L ) of rearranged immunoglobulin heavy and light chain genes using the Illumina MiSeq platform. We include complete protocols and primer sets for amplicon sequencing of V H /V H H/V L repertoires directly from human, mouse, and llama lymphocytes as well as from phage-displayed V H /V H H/V L libraries; these can be easily be adapted to other types of amplicons with little modification. The resulting amplicons are diverse and representative, even using as few as 10 3 input B cells, and their generation is relatively inexpensive, requiring no special equipment and only a limited set of primers. In the absence of heavy-light chain pairing, single-domain antibodies are uniquely amenable to NGS analyses. We present a number of applications of NGS technology useful in discovery of single-domain antibodies from phage display libraries, including: (i) assessment of library functionality; (ii) confirmation of desired library randomization; (iii) estimation of library diversity; and (iv) monitoring the progress of panning experiments. While the case studies presented here are of phage-displayed single-domain antibody libraries, the principles extend to other types of in vitro display libraries.

Monoclonal antibody form and function: manufacturing the right antibodies for treating drug abuse.

Science.gov (United States)

Peterson, Eric; Owens, S Michael; Henry, Ralph L

2006-05-26

Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus.

Science.gov (United States)

Bononi, Ilaria; Mazzoni, Elisa; Pietrobon, Silvia; Manfrini, Marco; Torreggiani, Elena; Rossini, Marika; Lotito, Francesca; Guerra, Giovanni; Rizzo, Paola; Martini, Fernanda; Tognon, Mauro

2018-08-01

JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS inducing the PML, (ii) the kidney of transplant patients causing the organ rejection. Association between JCPyV, which is a small DNA tumor virus, and gliomas and colorectal carcinomas has been published. In the present investigation, we report on a new indirect ELISA with two specific synthetic peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2-100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1 K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a docking site for serum antibodies. Data from this innovative immunologic assay indicate that the overall prevalence of JCPyV-VP1 antibodies in healthy subjects is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a useful method to detect specific IgG antibodies against this virus, without cross-reactivity with the closely related SV40 and BKPyV polyomaviruses. © 2018 Wiley Periodicals, Inc.

Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration1

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Gunes, Zeynep; Zucconi, Adriana; Cioce, Mario; Meola, Annalisa; Pezzanera, Monica; Acali, Stefano; Zampaglione, Immacolata; De Pratti, Valeria; Bova, Luca; Talamo, Fabio; Demartis, Anna; Monaci, Paolo; La Monica, Nicola; Ciliberto, Gennaro; Vitelli, Alessandra

2011-01-01

RON belongs to the c-MET family of receptor tyrosine kinases. As its well-known family member MET, RON and its ligand macrophage-stimulating protein have been implicated in the progression and metastasis of tumors and have been shown to be overexpressed in cancer. We generated and tested a large number of human monoclonal antibodies (mAbs) against human RON. Our screening yielded three high-affinity antibodies that efficiently block ligand-dependent intracellular AKT and MAPK signaling. This effect correlates with the strong reduction of ligand-activated migration of T47D breast cancer cell line. By cross-competition experiments, we showed that the antagonistic antibodies fall into three distinct epitope regions of the RON extracellular Sema domain. Notably, no inhibition of tumor growth was observed in different epithelial tumor xenografts in nude mice with any of the antibodies. These results suggest that distinct properties beside ligand antagonism are required for anti-RON mAbs to exert antitumor effects in vivo. PMID:21286376

Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

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Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

2000-01-01

The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

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Xu Chun-Ling

2011-11-01

Full Text Available Abstract Background Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. Case presentation A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. Conclusions Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year

Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS). Treatment effects and relation to coronary angiographic progression.

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Mack, W J; Krauss, R M; Hodis, H N

1996-05-01

Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease. Using data from the Monitored Atherosclerosis Regression Study, an angiographic trial of middle-aged men and women randomized to lovastatin or placebo, we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis. Coronary artery lesion progression was determined by quantitative coronary angiography in low-grade ( or = 50% diameter stenosis), and all coronary artery lesions in 220 baseline/2-year angiogram pairs. Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis. All low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) masses were significantly lowered and all high density lipoprotein (HDL) masses were significantly raised with lovastatin therapy. The mass of smallest LDL (Svedberg flotation rate [Sf] 0 to 3), IDL (Sf 12 to 20), all VLDL subclasses (Sf 20 to 60, Sf 60 to 100, and Sf 100 to 400), and peak LDL flotation rate were significantly related to the progression of coronary artery lesions, specifically low-grade lesions. Greater baseline levels of HDL3, were related to a lower likelihood of coronary artery lesion progression. In multivariate analyses, small VLDL (Sf 20 to 60) and HDL3 mass were the most important correlates of coronary artery lesion progression. These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease. In addition, these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions. More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins.

The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer.

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Wei, Ming; Shen, Duo; Mulmi Shrestha, Sachin; Liu, Juan; Zhang, Junyi; Yin, Ying

2018-01-01

Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+ T cell, memory cell, and so on, and each of them has special function on antitumor response or tumor immune escape which is revealed in lung cancer, colorectal cancer, breast cancer, ovarian cancer, and so on. But its correlation with gastric cancer is not clear. Our review was preformed to explore the relationship between the progress and prognosis of gastric cancer (GC) and T cell immunity. According to recent researches, T cell immunity may have an important role in the progress and prognosis of GCs, but its function is affected by location, category, related molecule, and interaction between the cells, and some effects still are controversial. More researches are needed to clarify this correlation.

Novel flow cytometric analysis of the progress and route of internalization of a monoclonal anti-carcinoembryonic antigen (CEA) antibody.

Science.gov (United States)

Ford, C H; Tsaltas, G C; Osborne, P A; Addetia, K

1996-03-01

A flow cytometric method of studying the internalization of a monoclonal antibody (Mab) directed against carcinoembryonic antigen (CEA) has been compared with Western blotting, using three human colonic cancer cell lines which express varying amounts of the target antigen. Cell samples incubated for increasing time intervals with fluoresceinated or unlabelled Mab were analyzed using flow cytometry or polyacrylamide gel electrophoresis and Western blotting. SDS/PAGE analysis of cytosolic and membrane components of solubilized cells from the cell lines provided evidence of non-degraded internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 min. Internalized anti-CEA was detected in the case of high CEA expressing cell lines (LS174T, SKCO1). Very similar results were obtained with an anti-fluorescein flow cytometric assay. Given that these two methods consistently provided comparable results, use of flow cytometry for the detection of internalized antibody is suggested as a rapid alternative to most currently used methods for assessing antibody internalization. The question of the endocytic route followed by CEA-anti-CEA complexes was addressed by using hypertonic medium to block clathrin mediated endocytosis.

Amended Final Report - Antibodies to Radionuclides. Engineering by Surface Display for Immunosensors

Energy Technology Data Exchange (ETDEWEB)

Blake, Diane A. [Tulane Univ., New Orleans, LA (United States)

2013-06-14

The relatively new techniques of antibody display, which permit molecular engineering of antibody structure and function, have the potential to revolutionize the way scientists generate binding proteins for specific applications. However, the skills required to efficiently use antibody display techniques have proven difficult for other laboratories to acquire without hands-on training and exchange of laboratory personnel. This research project is designed bring important expertise in antibody display to the State of Louisiana while pursuing a project with direct relevance to the DOE’s EM program.

Use of radiolabeled antibodies as diagnostic imaging agents

International Nuclear Information System (INIS)

Wang, T.S.T.; Seldin, D.; Fawwaz, R.A.; Srivastava, S.; Olvwole, S.

1989-01-01

Recent advances in hybridoma technology have led to the development of monoclonal antibodies to a variety of antigens. The high degree of specificity of such reagents coupled with refinements in instrumentation and production of new radionuclides has rekindled interest in the application of radioimmunoscintigraphy in the diagnosis of various diseases. Although much of the work with monoclonal antibodies has been devoted to the diagnosis and treatment of tumors, increasing use is being made of these agents for the study of nontumor related disorders. This chapter focuses on the application of radioimmunoscintigraphy in the diagnosis of malignancies with a discussion on the other uses, notably those related to the vascular system

Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria.

Science.gov (United States)

Hayman, L; Steffen, M J; Stevens, J; Badger, E; Tempro, P; Fuller, B; McGuire, A; Al-Sabbagh, Mohanad; Thomas, M V; Ebersole, J L

2011-04-01

Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. This study examined the ability of the host immune system to discriminate commensal oral bacteria from pathogens at mucosal surfaces, i.e. oral cavity. Serum immunoglobulin (Ig)G antibody reactive with three pathogenic and five commensal oral bacteria in 301 current smokers (age range 21-66 years) were examined by enzyme-linked immunosorbent assay. Clinical features of periodontal health were used as measures of periodontitis. Antibody to the pathogens and salivary cotinine levels were related positively to disease severity; however, the antibody levels were best described by the clinical disease unrelated to the amount of smoking. The data showed a greater immune response to pathogens than commensals that was related specifically to disease extent, and most noted in black males. Significant correlations in individual patient responses to the pathogens and commensals were lost with an increasing extent of periodontitis and serum antibody to the pathogens. Antibody to Porphyromonas gingivalis was particularly distinct with respect to the discriminatory nature of the immune responses in recognizing the pathogens. Antibody responses to selected pathogenic and commensal oral microorganisms differed among racial groups and genders. The antibody response to the pathogens was related to disease severity. The level of antibody to the pathogens, and in particular P. gingivalis, was correlated with disease severity in black and male subsets of patients. The amount of smoking did not appear to impact directly serum antibody levels to these oral bacteria. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Antibodies to co-trimoxazole (trimethoprim and/or sulfamethoxazole) related to the presence of the drug in a commercial low-ionic-strength solution.

Science.gov (United States)

Pham, Bach-Nga; Gien, Dominique; Bensaad, Farid; Babinet, Jérome; Dubeaux, Isabelle; Rouger, Philippe; Le Pennec, Pierre-Yves

2012-04-01

Drug-dependent antibodies have been associated with approximately 10% of acquired immune hemolytic anemia cases. These antibodies are a rare cause of interference in pretransfusion red blood cell (RBC) serologic testing. The aim of this work was to report three cases of subjects developing antibodies against co-trimoxazole, a combination of trimethoprim (TMP) and sulfamethoxazole (SMX). Blood samples of donor/patients were referred to our laboratory for the exploration of a positive antibody detection test. There was no recent history of drug taking. Antibody identification was performed by gel test using an indirect antiglobulin test, with reagent RBCs in low-ionic-strength solutions (LISS) containing co-trimoxazole or not. All three sera showed positive reactions when RBCs were resuspended in LISS containing co-trimoxazole, but negative reactions when RBCs were resuspended in LISS without antibiotic. We detected antibodies against co-trimoxazole showing three different antibody patterns: anti-TMP plus anti-SMX, anti-TMP alone, or anti-SMX alone. Anti-TMP showed an apparent anti-Ku specificity in the two cases where it was present. Anti-SMX showed an apparent anti-H specificity in one of the two cases described. The drug-dependent antibodies were not associated with acquired hemolytic anemia or other pathologies. Antibodies against co-trimoxazole may only be detected when using a diluent for reagent RBCs containing the drug in question. Antibody pattern (anti-TMP and/or anti-SMX) may vary according to individuals' immune response. Drug-dependent antibodies may react as antibodies against a high-prevalence antigen, supporting the hypothesis of antibodies to drug and membrane components. Drug-dependent antibodies such as anti-co-trimoxazole may be a serologic finding without clinical features. © 2011 American Association of Blood Banks.

Antibodies against alpha-synuclein reduce oligomerization in living cells.

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Thomas Näsström

Full Text Available Recent research implicates soluble aggregated forms of α-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which α-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing α-synuclein fused to hemi:GFP constructs to study the effects of α-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. C-terminal and oligomer-selective α-synuclein antibodies reduced the extent of α-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower α-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of α-synuclein, thus providing further support for passive immunization against diseases with α-synuclein pathology.

Antibodies to voltage-gated potassium and calcium channels in epilepsy.

Science.gov (United States)

Majoie, H J Marian; de Baets, Mark; Renier, Willy; Lang, Bethan; Vincent, Angela

2006-10-01

To determine the prevalence of antibodies to ion channels in patients with long standing epilepsy. Although the CNS is thought to be protected from circulating antibodies by the blood brain barrier, glutamate receptor antibodies have been reported in Rasmussen's encephalitis, glutamic acid decarboxylase (GAD) antibodies have been found in a few patients with epilepsy, and antibodies to voltage-gated potassium channels (VGKC) have been found in a non-paraneoplastic form of limbic encephalitis (with amnesia and seizures) that responds to immunosuppressive therapy. We retrospectively screened sera from female epilepsy patients (n=106) for autoantibodies to VGKC (Kv 1.1, 1.2 or 1.6), voltage-gated calcium channels (VGCC) (P/Q-type), and GAD. All positive results, based on the values of control data [McKnight, K., Jiang, Y., et al. (2005). Serum antibodies in epilepsy and seizure-associated disorders. Neurology 65, 1730-1735], were retested at lower serum concentrations, and results compared with previously published control data. Demographics, medical history, and epilepsy related information was gathered. The studied group consisted predominantly of patients with long standing drug resistant epilepsy. VGKC antibodies were raised (>100 pM) in six patients. VGCC antibodies (>45 pM) were slightly raised in only one patient. GAD antibodies were VGKC antibodies differed from previously described patients with limbic encephalitis-like syndrome, and were not different with respect to seizure type, age at first seizure, duration of epilepsy, or use of anti-epileptic drugs from the VGKC antibody negative patients. The results demonstrate that antibodies to VGKC are present in 6% of patients with typical long-standing epilepsy, but whether these antibodies are pathogenic or secondary to the primary disease process needs to be determined.

IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA.

Science.gov (United States)

Klöhn, Peter-Christian; Wuellner, Ulrich; Zizlsperger, Nora; Zhou, Yu; Tavares, Daniel; Berger, Sven; Zettlitz, Kirstin A; Proetzel, Gabriele; Yong, May; Begent, Richard H J; Reichert, Janice M

2013-01-01

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3-6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3-5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4-5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society's special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5-6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy.

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

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Swetha Tati

2017-09-01

Full Text Available JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11. Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures. The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity. The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry. Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy. Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1 suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice. Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status

DEFF Research Database (Denmark)

Løgstrup, Brian B; Masic, D.; Laurbjerg, T. B.

2017-01-01

Objectives: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation...... assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years. Results: Patients with elevated anti-CCP at baseline...

Generation of HER2 monoclonal antibodies using epitopes of a rabbit polyclonal antibody.

Science.gov (United States)

Hu, Francis Jingxin; Uhlen, Mathias; Rockberg, Johan

2014-01-25

One of the issues in using polyclonal antibodies is the limited amount of reagent available from an immunisation, leading to batch-to-batch variation and difficulties in obtaining the same antibody performance when the same antigen is re-immunised into several separate animals. This led to the development of hybridoma technology allowing, at least theoretically, for an unlimited production of a specific binder. Nevertheless, polyclonal antibodies are widely used in research and diagnostics and there exists a need for robust methods to convert a polyclonal antibody with good binding performance into a renewable monoclonal with identical or similar binding specificity. Here we have used precise information regarding the functional recognition sequence (epitope) of a rabbit polyclonal antibody with attractive binding characteristics as the basis for generation of a renewable mouse monoclonal antibody. First, the original protein fragment antigen was used for immunisation and generation of mouse hybridoma, without obtaining binders to the same epitope region. Instead a peptide designed using the functional epitope and structural information was synthesised and used for hybridoma production. Several of the monoclonal antibodies generated were found to have similar binding characteristics to those of the original polyclonal antibody. These monoclonal antibodies detected native HER2 on cell lines and were also able to stain HER2 in immunohistochemistry using xenografted mice, as well as human normal and cancer tissues. Copyright © 2013 Elsevier B.V. All rights reserved.

Antiphospholipid Antibody Induced by Nivolumab

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Ahmed Aburahma

2018-01-01

Full Text Available Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

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Akiba, Hiroki; Tsumoto, Kouhei

2015-07-01

Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

The interfacial character of antibody paratopes: analysis of antibody-antigen structures.

Science.gov (United States)

Nguyen, Minh N; Pradhan, Mohan R; Verma, Chandra; Zhong, Pingyu

2017-10-01

In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen. Furthermore, antibody-antigen interactions can be mediated by interfacial waters. However, there is no reported comprehensive analysis for a large number of structured waters that engage in higher ordered structures at the antibody-antigen interface. From our dataset, we have found the presence of interfacial waters in 242 complexes. We present evidence that suggests a compelling role of these interfacial waters in interactions of antibodies with a range of antigens differing in shape complementarity. Finally, we carry out 296 835 pairwise 3D structure comparisons of 771 structures of contact residues of antibodies with their interfacial water molecules from our dataset using CLICK method. A heuristic clustering algorithm is used to obtain unique structural similarities, and found to separate into 368 different clusters. These clusters are used to identify structural motifs of contact residues of antibodies for epitope binding. This clustering database of contact residues is freely accessible at http://mspc.bii.a-star.edu.sg/minhn/pclick.html. minhn@bii.a-star.edu.sg, chandra@bii.a-star.edu.sg or zhong_pingyu@immunol.a-star.edu.sg. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease

KAUST Repository

Vangone, Anna

2014-07-30

Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.

Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease

KAUST Repository

Vangone, Anna; Abdel-Azeim, Safwat; Caputo, Ivana; Sblattero, Daniele; Di Niro, Roberto; Cavallo, Luigi; Oliva, Romina

2014-01-01

Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.

Current role of antibody therapy in patients with metastatic colorectal cancer

DEFF Research Database (Denmark)

Pfeiffer, P; Qvortrup, C; Eriksen, Jesper Grau

2007-01-01

progressive disease and unfortunately in patients with disease resistant to 5-fluorouracil/folinic acid, irinotecan and oxaliplatin, no effective cytotoxic therapy is known. The rapidly expanding knowledge in tumor biology has encouraged optimism for the possibility to find and target tumor...... arsenal in CRC to a great extent, but they will also add to the complexity of treatment of CRC. In this review, we summarize the current status of antibody therapy in patients with CRC. Udgivelsesdato: 2007-May-28...

PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

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Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

[Influence of dendritic cell infiltration on prognosis and biologic characteristics of progressing gastric cancer].

Science.gov (United States)

Huang, Hai-li; Wu, Ben-yan; You, Wei-di; Shen, Ming-shi; Wang, Wen-ju

2003-09-01

To study the relation between dendritic cell (DC) infiltration and clinicopathologic parameters, biologic characteristics and prognosis of progressing gastric cancer. The development of apoptotic cell death (apoptotic index, AI) in 61 progressing gastric carcinoma tissues was analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. The PCNA labeling index (PCNA-LI), density of dendritic cells in the tumor were detected by immunohistochemical method by the LSAB kit using antibody against S-100 protein and PC-10. DC infiltration was negatively correlated with lymph node metastasis, clinical stage and PCNA-LI, but positively with AI. The DCs in gastric cancer groups with and without lymph node metastasis were (5.63 +/- 4.37)/HPF and (8.51 +/- 5.57)/HPF with difference significant (P stage lesions were (11.23 +/- 6.05)/HPF, (6.28 +/- 4.37)/HPF and (5.53 +/- 5.19)/HPF also with differences significant (P gastric carcinoma.

Mouse-specific antibody responses to a monoclonal antibody during repeated immunoscintigraphy investigations: Comparison of antibody titres and imaging studies in a rat model

International Nuclear Information System (INIS)

Pimm, M.V.; Gribben, S.J.; Markham, A.J.; Perkins, A.C.

1990-01-01

As a model for human mouse-specific antibody responses in patients undergoing immunoscintigraphy, we have investigated in rats the production of mouse-specific antibodies (MA) to the mouse monoclonal antibody 791T/36. At intervals of between 5 and 16 weeks the rats were given repeated cycles of intravenous (IV) injections of antibody with or without a simultaneous intradermal (ID) injection. The IV dose was 60 μg/kg, a dose similar to that used in many clinical immunoscintigraphy studies. The ID injection was 2 μg, which mimicks the skin test dose often given in clinical imaging protocols. The study was carried out with both 131 I-labelled antibody and with antibody labelled with 111 In by DTPA chelation. MA was measured with a passive haemagglutination assay using sheep red blood cells coated with the monoclonal antibody. Of rats given ID injections of unlabelled antibody at the same time as the IV imaging doses, 9/20 produced MA during 4 cycles of injections. In contrast, only 2/16 rats given only the IV dose produced MA. Both 131 I- and 111 In-labelled antibody appeared equally immunogenic with 5/18 and 6/18 overall responders, respectively. The production of MA was associated with a significant perturbation in the biodistribution of the IV dose of labelled antibody as seen by gamma-camera imaging of the rats given 111 In-labelled antibody. There was clearance of immune complexes to the liver, this organ accumulating up to 90% of the whole body count rate of radiolabel. MA titres of between 1/100 and 1/78000 caused equal perturbation of biodistribution, although below 1/100 the effect was more variable. (orig.)

Single-Domain Antibodies As Therapeutics against Human Viral Diseases

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Yanling Wu

2017-12-01

Full Text Available In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1, influenza viruses, hepatitis C virus (HCV, respiratory syncytial virus (RSV, and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

Antibodies to poliovirus detected by immunoradiometric assay with a monoclonal antibody

International Nuclear Information System (INIS)

Spitz, M.; Fossati, C.A.; Schild, G.C.; Spitz, L.; Brasher, M.

1982-01-01

An immunoradiometric assay (IRMA) for the assay of antibodies to poliovirus antigens is described. Dilutions of the test sera or whole (finger prick) blood samples were incubated with the poliovirus antigen bound to a solid phase and the specific antibody was detected by the addition of a mouse anti-human IgG monoclonal antibody (McAb), which was itself revealed by iodinated sheep IgG antimouse F(ab). The authors have shown that this technique is suitable for the estimation of IgG anti-poliovirus antibodies induced in children following polio vaccine. The present study shows that SPRIA provides a simple and inexpensive method for serological studies with poliovirus particularly for use in large-scale surveys. (Auth.)

Antibodies to poliovirus detected by immunoradiometric assay with a monoclonal antibody

Energy Technology Data Exchange (ETDEWEB)

Spitz, M.; Fossati, C.A.; Schild, G.C.; Spitz, L.; Brasher, M. (National Inst. for Biological Standards and Control, London (UK))

1982-10-01

An immunoradiometric assay (IRMA) for the assay of antibodies to poliovirus antigens is described. Dilutions of the test sera or whole (finger prick) blood samples were incubated with the poliovirus antigen bound to a solid phase and the specific antibody was detected by the addition of a mouse anti-human IgG monoclonal antibody (McAb), which was itself revealed by iodinated sheep IgG antimouse F(ab). The authors have shown that this technique is suitable for the estimation of IgG anti-poliovirus antibodies induced in children following polio vaccine. The present study shows that SPRIA provides a simple and inexpensive method for serological studies with poliovirus particularly for use in large-scale surveys.

IgE antibodies to Hymenoptera venoms in the serum are common in the general population and are related to indications of atopy.

Science.gov (United States)

Schäfer, T; Przybilla, B

1996-06-01

Determination of Hymenoptera venom (HV)-specific serum IgE antibodies is a useful diagnostic method in patients with systemic anaphylactic reaction (SAR) to Hymenoptera stings. In a general population cohort, we determined the prevalence of SAR and HV-specific IgE antibodies and assessed parameters associated with the latter. A total of 277 voluntarily participating inhabitants of rural Bavaria (Germany) (232 adults, mean age 38.0 years; 45 children, mean age 8.4 years) were investigated for a history of atopic disease or SAR to insect stings; in 258 of these, total IgE and specific IgE antibodies to HV (Apis mellifera, Vespula vulgaris/germanica) and four common aeroallergens (birch pollen, grass pollen, house-dust mite, and cat dander) in the serum were determined. Nine (3.3%) subjects reported SAR to insect stings. In 27.1% of the sera, specific IgE antibodies to HV were found, to bee venom in 24.8%, and to wasp venom in 8.5% (P 100 kU/l was found in 22.5%. Specific serum IgE to HV was significantly associated with male sex (female vs. male, OR = 0.47; CI 0.25-0.86), young age (children vs. adults, OR = 2.80; CI 1.25-6.28), a history of SAR to insect stings (OR = 4.16; CI 1.15-15.03), total sIgE > 100 kU/l (OR = 3.88; CI 1.98-7.60), and specific IgE antibodies to three of the four aeroallergens (grass pollen, OR = 7.24 CI 3.66-14.38; birch pollen, OR = 3.67 CI 1.54-8.81; and house-dust mite, OR = 4.61 CI 2.08-10.32). It is concluded that immunologic sensitization to HV is common in the general population and is associated with atopy-related humoral IgE hyperresponsiveness.

Antibody response to a synthetic peptide covering a LAV-1/HTLV-IIIB neutralization epitope and disease progression

NARCIS (Netherlands)

Boucher, C. A.; de Wolf, F.; Houweling, J. T.; Bakker, M.; Dekker, J.; Roos, M. T.; Coutinho, R. A.; van der Noordaa, J.; Goudsmit, J.

1989-01-01

Sequential sera of homosexual men participating in a prospective study on the incidence of HIV-1 infection and risk factors for AIDS were tested for the presence of antibodies to a synthetic 17-mer (Neu21; KSIRIQRGPGRAFVTIG) representing a neutralization epitope as present on the LAV-1/HTLV-IIIB

Monoclonal antibodies for treating cancer

International Nuclear Information System (INIS)

Dillman, R.O.

1989-01-01

The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

Heavy chain only antibodies

DEFF Research Database (Denmark)

Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

2013-01-01

Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

Science.gov (United States)

Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

2016-08-01

Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases.

Science.gov (United States)

Allenbach, Y; Benveniste, O

2015-01-01

To date, there are four main groups of idiopathic inflammatory myopathies (IIM): polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis; based on clinical presentation and muscle pathology. Nevertheless, important phenotypical differences (either muscular and/or extra-muscular manifestations) within a group persist. In recent years, the titration of different myositis-specific (or associated) auto-antibodies as a diagnostic tool has increased. This is an important step forward since it may facilitate, at a viable cost, the differential diagnosis between IIM and other myopathies. We have now routine access to assays for the detection of different antibodies. For example, IMNM are related to the presence of anti-SRP or anti-HMGCR. PM is associated with anti-synthetase antibodies (anti-Jo-1, PL-7, PL-12, OJ, and EJ) and DM with anti-Mi-2, anti-SAE, anti-TIF-1-γ and anti-NXP2 (both associated with cancer) or anti-MDA5 antibodies (associated with interstitial lung disease). Today, over 30 myositis specific and associated antibodies have been characterised, and all groups of myositis may present one of those auto-antibodies. Most of them allow identification of homogenous patient groups, more precisely than the classical international classifications of myositis. This implies that classification criteria could be modified accordingly, since these auto-antibodies delineate groups of patients suffering from myositis with consistent clinical phenotype (muscular and extra-muscular manifestations), common prognostic (cancer association, presence of interstitial lung disease, mortality and risk of relapse) and treatment responses. Nevertheless, since numerous auto-antibodies have been recently characterised, the exact prevalence of myositis specific antibodies remains to be documented, and research of new auto-antibodies in the remaining seronegative group is still needed.

Characterization of product-related low molecular weight impurities in therapeutic monoclonal antibodies using hydrophilic interaction chromatography coupled with mass spectrometry.

Science.gov (United States)

Wang, Shunhai; Liu, Anita P; Yan, Yuetian; Daly, Thomas J; Li, Ning

2018-05-30

Traditional SDS-PAGE method and its modern equivalent CE-SDS method are both widely applied to assess the purity of therapeutic monoclonal antibody (mAb) drug products. However, structural identification of low molecular weight (LMW) impurities using those methods has been challenging and largely based on empirical knowledges. In this paper, we present that hydrophilic interaction chromatography (HILIC) coupled with mass spectrometry analysis is a novel and orthogonal method to characterize such LMW impurities present within a purified mAb drug product sample. We show here that after removal of N-linked glycans, the HILIC method separates mAb-related LMW impurities with a size-based elution order. The subsequent mass measurement from a high-resolution accurate mass spectrometer provides direct and unambiguous identification of a variety of low-abundance LMW impurities within a single LC-MS analysis. Free light chain, half antibody, H2L species (antibody possessing a single light chain) and protein backbone-truncated species can all be confidently identified and elucidated in great detail, including the truncation sites and associated post-translational modifications. It is worth noting that this study provides the first example where the H2L species can be directly detected in a mAb drug product sample by intact mass analysis without prior enrichment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Polyclonal and monoclonal antibodies in clinic.

Science.gov (United States)

Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

2014-01-01

Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

Seroprevalence of human papillomavirus immunoglobulin G antibodies among women presenting at the reproductive health clinic of a university teaching hospital in Nigeria.

Science.gov (United States)

Aminu, M; Gwafan, Jz; Inabo, Hi; Oguntayo, Ao; Ella, Ee; Koledade, Ak

2014-01-01

Human papillomavirus (HPV) is the cause of 90%-95% of squamous cell cancers. Persistent infection with high-risk HPV can lead to development of precancerous lesions of the cervix in 5%-10% of infected women, and can progress to invasive cervical cancer 15-20 years later. This study was conducted to determine the seroprevalence of HPV immunoglobulin G (IgG) antibodies among women of reproductive age attending a reproductive health clinic at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. The study was descriptive, cross-sectional, and experimental, combining the use of a structured questionnaire and analysis of serum samples obtained from 350 consecutive consenting women. The serum samples were analyzed for IgG antibodies to HPV by enzyme-linked immunosorbent assay. We found a seroprevalence of 42.9% (150/350) for IgG antibodies to HPV in these women. Women aged 45-49 years and those who had their sexual debut aged 20-23 years had the highest HPV seroprevalence, ie, 50% (57/114) and 51.1% (46/90), respectively. Presence of antibodies varied according to sociodemographic factors, but was significantly associated with educational status, tribe, and religion (Pwomen. Antibodies to HPV were detected in 50.0% (9/18) of women with a family history of cervical cancer and in 30.8% (4/13) of those with a history or signs of WHIM (warts, hypogammaglobulinemia, immunodeficiency, myelokathexis) syndrome as a genetic disorder (P>0.05). Further studies are needed to determine the HPV serotypes and evaluate the risk of natural development of HPV-related malignancies among women in the study area.

Sleep-Related Eating Disorder: A Case Report of a Progressed Night Eating Syndrome

Directory of Open Access Journals (Sweden)

Sayed Shahabuddin Hoseini

2012-07-01

Full Text Available Night eating syndrome is a common disorder in eating behaviors that occurs in close relation to the night time sleep cycle. Although eating disorders are common in society, night eating syndrome has been left neglected by health care professionals. In this report we present a case of eating disorder that exhibits some novel features of night eating syndrome. Our case was a progressed type of eating disorder which may increase awareness among physicians about sleep-related eating disorders.

Acetylcholine receptor antibody

Science.gov (United States)

... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library.

Science.gov (United States)

Adler, Adam S; Bedinger, Daniel; Adams, Matthew S; Asensio, Michael A; Edgar, Robert C; Leong, Renee; Leong, Jackson; Mizrahi, Rena A; Spindler, Matthew J; Bandi, Srinivasa Rao; Huang, Haichun; Tawde, Pallavi; Brams, Peter; Johnson, David S

2018-04-01

Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method. 30% of the natively paired scFv binders were also discovered with the randomly paired method, and 13% of the randomly paired binders were also discovered with the natively paired method. Additionally, 33% of the scFv binders discovered only in the randomly paired library were initially present in the natively paired pre-sort library. Thus, a significant proportion of "randomly paired" scFv were actually natively paired. We synthesized and produced 46 of the candidates as full-length antibodies and subjected them to a panel of binding assays to characterize their therapeutic potential. 87% of the antibodies were verified as binding IL-21R by at least one assay. We found that antibodies with native light chains were more likely to bind IL-21R than antibodies with non-native light chains, suggesting a higher false positive rate for antibodies from the randomly paired library. Additionally, the randomly paired method failed to identify nearly half of the true natively paired binders, suggesting a higher false negative rate. We conclude that natively paired libraries have critical advantages in sensitivity and specificity for antibody discovery programs.

Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies

Directory of Open Access Journals (Sweden)

Fa Yang

2016-12-01

Full Text Available With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent or acquired resistance and to be more efficient angiogenesis inhibitors. Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies also have broad application prospects in bone disorders and infections and diseases of the central nervous system. The latest developments of the formats and application of bispecific antibodies will be reviewed. Furthermore, the challenges and perspectives are summarized in this review.

Radiolabeled antibody in the detection of infection using endocarditis as a model

International Nuclear Information System (INIS)

Mishkin, F.S.; Wong, D.W.; Dhawan, V.K.; Reese, I.C.; Thadepalli, H.

1983-01-01

The authors have examined a method to detect infections using radiolabeled antibodies. Staphylococcal endocarditis was chosen as a model because it poses a common clinical diagnostic problem. The experiments demonstrate that biologically active antibodies may be extracted and efficiently labeled by a relatively simple process. This has the potential to make the specificity of the in vivo antigen-antibody reaction available through the use of autologously extracted, labeled γ-globulin

Re-engineering therapeutic antibodies for Alzheimer's disease as blood-brain barrier penetrating bi-specific antibodies.

Science.gov (United States)

Pardridge, William M

2016-12-01

Therapeutic antibodies are large molecule drugs that do not cross the blood-brain barrier (BBB). Therefore, drug development of therapeutic antibodies for Alzheimer's disease (AD) requires that these molecules be re-engineered to enable BBB delivery. This is possible by joining the therapeutic antibody with a transporter antibody, resulting in the engineering of a BBB-penetrating bispecific antibody (BSA). Areas covered: The manuscript covers transporter antibodies that cross the BBB via receptor-mediated transport systems on the BBB, such as the insulin receptor or transferrin receptor. Furthermore, it highlights therapeutic antibodies for AD that target the Abeta amyloid peptide, beta secretase-1, or the metabotropic glutamate receptor-1. BSAs are comprised of both the transporter antibody and the therapeutic antibody, as well as IgG constant region, which can induce immune tolerance or trigger transport via Fc receptors. Expert opinion: Multiple types of BSA molecular designs have been used to engineer BBB-penetrating BSAs, which differ in valency and spatial orientation of the transporter and therapeutic domains of the BSA. The plasma pharmacokinetics and dosing regimens of BSAs differ from that of conventional therapeutic antibodies. BBB-penetrating BSAs may be engineered in the future as new treatments of AD, as well as other neural disorders.

Antinuclear antibody panel

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

Development of antibody against sulfamethazine

International Nuclear Information System (INIS)

Li Ziying; Xi Wenge; Liu Yibing; Zhang Liling; Guo Weizheng; Han Shiquan

2004-01-01

Sulfamethazine (SMT) is widely used to treat bacterial and protozoan infections in food animals. So its residue has been detected in various food products, and in Europe, the tolerance level for sulfonamides in meat and milk is 100 ng/g. To ensure that residues in animal food products do not exceed this limit, a simple, sensitive, and rapid method to determinate their residues in animal tissues is needed. In this paper the development of polyclonal or monoclonal antibodies against sulfamethazine (SMT) and a simplified method to identify residual sulfamethazine by radio immunoassay (RIA) is presented. Polyclonal antibodies (PcAbs) against sulfamethazine (SMT) were obtained by immunizing rabbits with SMT-conjugated bovine serum albumin (BSA). The association constants (Ka) of the PcAbs were higher than 108 and the cross-reactivities with Sulfadiazine(SD), Sulfaquinoxaline(SQX) which were structurally related compounds were lower than 0.05%(RIA). Simultaneous, six strains of hybridoma cell were prepared which can secrete monoclonal antibodies (McAbs) against SMT . The Ka of the McAbs against SMT were higher than 107 and the cross-reactivities with SD, SQX were lower than 0.1%(RIA). (authors)

Tumor imaging with monoclonal antibodies

International Nuclear Information System (INIS)

Haisma, H.; Hilgers, J.

1987-01-01

Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123 I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111 In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab) 2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

Radioimmunoassay of class-specific antibodies (RIACA): chicken antibodies to DNP

International Nuclear Information System (INIS)

Viljanen, M.K.; Granfors, K.; Toivanen, P.

1977-01-01

A radioimmunological method for the quantitation of class-specific antibodies has been developed. The method allows the quantitation of nanogram per ml concentrations of IgG and IgM-anti-DNP antibodies without any physical or chemical pretreatment of the sample. DNP was coupled covalently to a cyanogen bromide activated paper disk with the augmentation of lysine molecule. Anti-DNP antibodies were allowed to react with the coupled DNP and then quantitated by their capacity to bind 125 I-labelled anti-chicken-μ or anti-chicken-γ. The inter-assay variation coefficients ranged from 8.1 to 14.7% and the mean standard deviations of duplicate determinations were about 11%. The combination of this method with the exact immunoradiometric quantitation of the total serum IgM and IgG, and with an immunoabsorption technique, makes it possible to quantitate class-specific antibodies on weight units

Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

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Jesse V. Schoen

2017-10-01

Full Text Available Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs, which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs and the membrane proximal external region (MPER of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude (p=0.0036 and breadth (p=0.0358 of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

[Construction of human phage antibody library and screening for human monoclonal antibodies of amylin].

Science.gov (United States)

Gong, Qian; Li, Chang-ying; Chang, Ji-wu; Zhu, Tie-hong

2012-06-01

To screen monoclonal antibodies to amylin from a constructed human phage antibody library and identify their antigenic specificity and combining activities. The heavy chain Fd fragment and light chain of human immunoglobulin genes were amplified from peripheral blood lymphocytes of healthy donors using RT-PCR, and then inserted into phagemid pComb3XSS to generate a human phage antibody library. The insertion of light chain or heavy chain Fd genes were identified by PCR after the digestion of Sac I, Xba I, Xho Iand Spe I. One of positive clones was analyzed by DNA sequencing. The specific anti-amylin clones were screened from antibody library against human amylin antigens and then the positive clones were determined by Phage-ELISA analysis. A Fab phage antibody library with 0.8×10(8); members was constructed with the efficacy of about 70%. DNA sequence analysis indicated V(H); gene belonged to V(H);3 gene family and V(λ); gene belonged to the V(λ); gene family. Using human amylin as panning antigen, specific anti-amylin Fab antibodies were enriched by screening the library for three times. Phage-ELISA assay showed the positive clones had very good specificity to amylin antigen. The successful construction of a phage antibody library and the identification of anti-amylin Fab antibodies provide a basis for further study and preparation of human anti-amylin antibodies.

Cell-free synthesis of functional antibody fragments to provide a structural basis for antibody-antigen interaction.

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Takayoshi Matsuda

Full Text Available Growing numbers of therapeutic antibodies offer excellent treatment strategies for many diseases. Elucidation of the interaction between a potential therapeutic antibody and its target protein by structural analysis reveals the mechanism of action and offers useful information for developing rational antibody designs for improved affinity. Here, we developed a rapid, high-yield cell-free system using dialysis mode to synthesize antibody fragments for the structural analysis of antibody-antigen complexes. Optimal synthesis conditions of fragments (Fv and Fab of the anti-EGFR antibody 059-152 were rapidly determined in a day by using a 30-μl-scale unit. The concentration of supplemented disulfide isomerase, DsbC, was critical to obtaining soluble antibody fragments. The optimal conditions were directly applicable to a 9-ml-scale reaction, with linear scalable yields of more than 1 mg/ml. Analyses of purified 059-152-Fv and Fab showed that the cell-free synthesized antibody fragments were disulfide-bridged, with antigen binding activity comparable to that of clinical antibodies. Examination of the crystal structure of cell-free synthesized 059-152-Fv in complex with the extracellular domain of human EGFR revealed that the epitope of 059-152-Fv broadly covers the EGF binding surface on domain III, including residues that formed critical hydrogen bonds with EGF (Asp355EGFR, Gln384EGFR, H409EGFR, and Lys465EGFR, so that the antibody inhibited EGFR activation. We further demonstrated the application of the cell-free system to site-specific integration of non-natural amino acids for antibody engineering, which would expand the availability of therapeutic antibodies based on structural information and rational design. This cell-free system could be an ideal antibody-fragment production platform for functional and structural analysis of potential therapeutic antibodies and for engineered antibody development.

Lyme disease antibody

Science.gov (United States)

... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

Analysis of ovine colostrum to detect antibody against progressive pneumonia virus.

OpenAIRE

Taylor, T B; Banowetz, G M; Schipper, I A; Gabrielson, D A

1982-01-01

Immunoglobulins were isolated and purified from the colostrum and serum of progressive pneumonia virus infected sheep and also from non-infected control sheep. Four classes of immunoglobulins were isolated from sheep colostrum (IgG1, IgG2, IgA and Ig10s). Three classes of immunoglobulins were isolated from sheep serum (IgG1, IgG2 and IgM). Low levels of virus neutralizing activity were demonstrated only in the whole serum and purified serum IgG1 preparations. No complement fixing activity was...

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

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Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

Application of murine monoclonal antibodies to the serodiagnosis of tuberculosis

International Nuclear Information System (INIS)

Ivanyl, J.; Coates, A.R.M.; Krambovitis, E.

1982-01-01

The immune response during infectious diseases leads to a rise in antibody titre to the various different antigenic determinants of the causative organism. The response is further complicated by the fact that it is relatively unusual for one individual to respond to all antigenic components of an organism. Demonstration of the specific immune response of an infected host by serological tests is often hampered by the broad cross-reactivity between several bacterial antigens. The authors report on a serodiagnostic application of murine monoclonal antibodies (MAB), specific for a human pathogen, M. tuberculosis by a technique which is applicable in principle to the serodiagnosis of many other infectious diseases. The serum diagnostic test is based on the competitive inhibition by human sera of the binding of 125 I-labelled murine monoclonal antibodies to M. tuberculosis-coated polyvinyl plates. Five monoclonal antibodies binding to distinct antigenic determinants of the organism were used as structural probes which conferred their stringent combining site specificities to the polyclonal mixture of antibodies from patients' sera. When compared with healthy controls, increased titres of inhibitory antibodies were found in about 70% of patients with active tuberculosis. The diagnostic value of the individual monoclonal antibodies as well as the benefit from the use of multiple specificity probes has been qualified

A systematic analysis of commonly used antibodies in cancer diagnostics.

Science.gov (United States)

Gremel, Gabriela; Bergman, Julia; Djureinovic, Dijana; Edqvist, Per-Henrik; Maindad, Vikas; Bharambe, Bhavana M; Khan, Wasif Ali Z A; Navani, Sanjay; Elebro, Jacob; Jirström, Karin; Hellberg, Dan; Uhlén, Mathias; Micke, Patrick; Pontén, Fredrik

2014-01-01

Immunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. A tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer. © 2013 John Wiley & Sons Ltd.

Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics.

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Bumbaca, Daniela; Boswell, C Andrew; Fielder, Paul J; Khawli, Leslie A

2012-09-01

Monoclonal antibodies are increasingly being developed to treat multiple disease areas, including those related to oncology, immunology, neurology, and ophthalmology. There are multiple factors, such as charge, size, neonatal Fc receptor (FcRn) binding affinity, target affinity and biology, immunoglobulin G (IgG) subclass, degree and type of glycosylation, injection route, and injection site, that could affect the pharmacokinetics (PK) of these large macromolecular therapeutics, which in turn could have ramifications on their efficacy and safety. This minireview examines how characteristics of the antibodies could be altered to change their PK profiles. For example, it was observed that a net charge modification of at least a 1-unit shift in isoelectric point altered antibody clearance. Antibodies with enhanced affinity for FcRn at pH 6.0 display longer serum half-lives and slower clearances than wild type. Antibody fragments have different clearance rates and tissue distribution profiles than full length antibodies. Fc glycosylation is perceived to have a minimal effect on PK while that of terminal high mannose remains unclear. More investigation is warranted to determine if injection route and/or site impacts PK. Nonetheless, a better understanding of the effects of all these variations may allow for the better design of antibody therapeutics.

Limbic encephalitis and antibodies to Ma2: a paraneoplastic presentation of breast cancer.

Science.gov (United States)

Sutton, I; Winer, J; Rowlands, D; Dalmau, J

2000-08-01

A patient with atypical medullary breast cancer is described who presented with symptoms of limbic encephalitis. The patient's serum and CSF contained antibodies that reacted with the nervous system and the tumour. These antibodies recognised Ma2, a neuronal protein related to paraneoplastic limbic and brainstem encephalitis in men with testicular tumours. This report highlights the importance of testing for paraneoplastic antineuronal antibodies in cases of unexplained limbic encephalitis and suggests screening for breast cancer in women with antibodies predominantly directed to Ma2.

Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates.

Science.gov (United States)

Xu, Shi

2015-11-01

This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.

Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

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Miroslava Bilecova-Rabajdova

2014-01-01

Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

[Research progress on ebola virus glycoprotein].

Science.gov (United States)

Ding, Guo-Yong; Wang, Zhi-Yu; Gao, Lu; Jiang, Bao-Fa

2013-03-01

Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans and there are no effective therapeutic or prophylactic treatments available. The glycoprotein (GP) of EBOV is a transmembrane envelope protein known to play multiple functions including virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. GP is the primary target of protective immunity and the key target for developing neutralizing antibodies. In this paper, the research progress on genetic structure, pathogenesis and immunogenicity of EBOV GP in the last 5 years is reviewed.

Antibody deposition in tumor in relation to blood clearance using a nephrectomized mouse model

International Nuclear Information System (INIS)

Nelp, W.B.; Eary, J.F.; Beaumier, P.; Krohn, K.A.; Hellstrom, K.E.; Hellstrom, I.

1985-01-01

The purpose of this experiment was to study tumor deposition of monoclonal anti-p97 melanoma antibody (Fab) as a function of its blood concentration over time. I-131-anti-p97 Fab and I-125 non-specific Fab were injected I.V. into 28 control athymic (nude) mice (CM) bearing human xenografted malignant melanoma containing p-97 antigen. Fab (M.W. 50,000) is rapidly excreted by kidney and >90% excretion occurred in 24 hr. To create maximum sustained high blood concentrations of Fab 10 similar mice were likewise injected 1 hr after acute nephrectomy (NM). In this case 24 hr. body excretion was <1%. Blood clearance in CM was biexponential with initial T-1/2 0.4 hr. (80%) a second T-1/2 of 4.4 hr. In NM clearance was monoexponential with a T-1/2 of 29.6 hr. Blood concentrations at 4 hrs. were 2 vs. 19% dose/gm (CM vs NM) and 0.15 vs 12 at 24 hrs. This tumor binding resembled a 2nd order phenomenon. Such information may be useful in predicting the effect of dosage manipulations (multiple bolus or sustained infusions) designed to increase Fab blood levels and enhance tumor labeling with Fab. The NM model should be useful to study the kinetics of antibody tumor deposition with various antibodies

Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis

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Kazutaka Kitaura

2017-05-01

Full Text Available A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM. Class-switch recombination (CSR produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V, junctional (J sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

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Katerina T. Xenaki

2017-10-01

Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

Characterisation of monoclonal antibodies for human luteinising hormone, and mapping of antigenic determinants on the hormone

International Nuclear Information System (INIS)

Soos, M.; Siddle, K.

1983-01-01

Twelve mouse monoclonal antibodies for human luteinising hormone were produced. The affinities varied from 4 X 10 7 to 1 X 10 10 l/mol. The specificity of each antibody was assessed by determining the relative reactivities with luteinising hormone, thyroid stimulating hormone, follicle stimulating hormone and chorionic gonadotrophin. Six antibodies bound to the α-subunit as shown by similar reactivity with all hormones, and the remainder to the β-subunit as shown by specificity for luteinising hormone. This latter group of antibodies cross-reacted only weakly with thyroid stimulating hormone (approximately 10%) and follicle stimulating hormone (approximately 3%). Three of these antibodies also showed low reactivity towards chorionic gonadotrophin (<10%), though the others did not (80-300%). The ability of different antibodies to bind simultaneously to luteinising hormone was examined and it was shown that several distinct antigenic determinants existed on both subunits. The characterisation of monoclonal binding sites is discussed in relation to the use of antibodies in two-site immunoradiometric assays. (Auth.)

Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier

International Nuclear Information System (INIS)

Friden, P.M.; Walus, L.R.; Musso, G.F.; Taylor, M.A.; Malfroy, B.; Starzyk, R.M.

1991-01-01

Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The authors have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration, labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate ∼ 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26

SPECT assay of radiolabeled monoclonal antibodies

International Nuclear Information System (INIS)

Jaszczak, R.J.

1992-02-01

The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ( 123 I, 131 I, and 111 In) and with another radionuclide, 211 At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for 111 In and 123 I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches

Increased levels of anti-glycan antibodies in patients with cystic fibrosis

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Hirche TO

2011-09-01

Full Text Available Abstract Background The prevalence of Crohn's disease (CD is increased in patients with cystic fibrosis (CF. Anti-Saccharomyces cerevisiae antibodies (ASCA have been suggested as a screening tool to detect CD in CF. Recently, several new anti-glycan antibodies have been reported in CD. Materials and methods The sera of 119 CF patients of various age groups were prospectively screened for ASCA type IgG (gASCA, anti-laminaribioside carbohydrate IgG antibodies (ALCA, anti-chitobioside carbohydrate IgA antibodies (ACCA, and anti-mannobioside carbohydrate IgG antibodies (AMCA. The frequency of these anti-glycan antibodies was then compared in patients with CD, ulcerative colitis, rheumatoid arthritis and healthy volunteers. Results A significant number of CF patients were positive for gASCA (51.3% [41.6-60.6] and up to three other anti-glycan antibodies concurrently. Serum levels of anti-glycan antibodies in CF and CD were not related to parameters of inflammation. Despite the well-documented difference in clinical course between male and female CF patients no gender difference of anti-glycan antibodies was found. In contrast, there was a significant positive correlation between anti-glycan markers and age in CF patients. Conclusions Our findings demonstrate for the first time the increased frequency of a panel of anti-glycan antibodies in CF and provide a link between the presence of these serological biomarkers and patient's age. Anti-glycan antibody profiling may therefore become a valuable tool in the care of patients with CF.

KADAR ANTIBODI-TIROPEROKSIDASE DAN ANTIBODI-TIROGLOBULIN PADA WANITA USIA SUBUR DI DAERAH ENDEMlS GAKI

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Agus Wibowo

2012-10-01

Full Text Available Background: Thyroid hormones play a critical role in human. Disorders of the thyroid gland result primary from autoimmune processes that either stimulate the over production of thyroid hormones (hyperthyroid or causes glandular destruction and hormones deficiency (hypothyroid. Autoimmune Thyroid Disease (AITD a common organ specific autoimmune disorder is seen mostly in women. AITD are complex disease that are caused by an interaction between susceptibility genes and environmental trigger such dietary iodine. The development of antibodies to Thyroid peroxidase (TPO and Thyroglobulin (TG is the main hall mark of AITD. Method: 'Thirty respondents from were analyzed. The blood were collected for TSH, FreeT4, Tyroglobulin Antibody and Tyroperoxidase Antibody analyzed and DNA isolation. Circulating TSH, FreeT4, autoantibodies to TPO and TG are measured by ELISA. Result: 50% respondent in normal thyroid hormones and 50% in hypothyroid and hyperthyroid status. TPO antibodies  and thyroglobulin antibodies found in all of respondent with thyroid disorder. Conclusion: Antibodies to TPO and TG is seen in respondent with thyroid disorder   Keywords: AITD, TSH, FreeT4, TPO antibodies, TG antibodies.

Monoclonal antibodies based on hybridoma technology.

Science.gov (United States)

Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

2013-03-01

Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs.

Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

Directory of Open Access Journals (Sweden)

Xinwei Wang

Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein.

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Mikael Kyrklund

Full Text Available Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44 of Porphyromonas gingivalis (Pg, a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/- mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS, and to phosphocholine (PCho were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis.

Tabhu: tools for antibody humanization

DEFF Research Database (Denmark)

Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

2015-01-01

Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...... elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity...... and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps...

Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

NARCIS (Netherlands)

Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

2017-01-01

The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

[An autopsy case of amyotrophic lateral sclerosis with prominent muscle cramps, fasciculation, and high titer of anti-voltage gated potassium channel (VGKC) complex antibody].

Science.gov (United States)

Sato, Aki; Sakai, Naoko; Shinbo, Junsuke; Hashidate, Hideki; Igarashi, Shuichi; Kakita, Akiyoshi; Yamazaki, Motoyoshi

2014-01-01

The patient was a 55-year-old male who had prominent fasciculation and muscle cramps. Muscle weakness and atrophy of the trunk, respiratory system, and extremities gradually progressed. On the basis of these features, we diagnosed this patient as having amyotrophic lateral sclerosis (ALS), however, the upper motor neuron signs were not significant. Following the detection of the anti-voltage gated potassium channel (VGKC) complex antibody at 907.5 pM (normal VGKC complex antibody in the development of cramp-fasciculation syndrome has been speculated. In this ALS patient, the antibodies might be associated with pathomechanisms underlying the characteristic symptoms.

HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody-drug conjugate design.

Science.gov (United States)

de Goeij, Bart E C G; Peipp, Matthias; de Haij, Simone; van den Brink, Edward N; Kellner, Christian; Riedl, Thilo; de Jong, Rob; Vink, Tom; Strumane, Kristin; Bleeker, Wim K; Parren, Paul W H I

2014-01-01

The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated by ado-trastuzumab emtansine (Kadcyla(TM)). While selecting a suitable antibody for an ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics of the optimal antibody candidate remain poorly understood. We studied a large panel of human HER2 antibodies to identify the characteristics that make them most suitable for an ADC approach. As a model toxin, amenable to in vitro high-throughput screening, we employed Pseudomonas exotoxin A (ETA') fused to an anti-kappa light chain domain antibody. Cytotoxicity induced by HER2 antibodies, which were thus non-covalently linked to ETA', was assessed for high and low HER2 expressing tumor cell lines and correlated with internalization and downmodulation of HER2 antibody-target complexes. Our results demonstrate that HER2 antibodies that do not inhibit heterodimerization of HER2 with related ErbB receptors internalize more efficiently and show greater ETA'-mediated cytotoxicity than antibodies that do inhibit such heterodimerization. Moreover, stimulation with ErbB ligand significantly enhanced ADC-mediated tumor kill by antibodies that do not inhibit HER2 heterodimerization. This suggests that the formation of HER2/ErbB-heterodimers enhances ADC internalization and subsequent killing of tumor cells. Our study indicates that selecting HER2 ADCs that allow piggybacking of HER2 onto other ErbB receptors provides an attractive strategy for increasing ADC delivery and tumor cell killing capacity to both high and low HER2 expressing tumor cells.

Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody

DEFF Research Database (Denmark)

Segal, Neil H; Logan, Theodore F; Hodi, F Stephen

2017-01-01

Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors...... and lymphoma.Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included...... the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines.Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg...

What Is Antiphospholipid Antibody Syndrome?

Science.gov (United States)

... Back To Health Topics / Antiphospholipid Antibody Syndrome Antiphospholipid Antibody Syndrome Also known as What Is Antiphospholipid (AN-te-fos-fo-LIP-id) antibody syndrome (APS) is an autoimmune disorder. Autoimmune disorders ...

Antibody engineering: methods and protocols

National Research Council Canada - National Science Library

Chames, Patrick

2012-01-01

"Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

Science.gov (United States)

Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

Directory of Open Access Journals (Sweden)

Dong Hyun Jo

Full Text Available Anti-vascular endothelial growth factor (VEGF agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Designing two-in-one antibodies.

Science.gov (United States)

Valladares, Ignacio Garcia; Espinoza, Luis R

2009-09-01

Evaluation of: Bostrom J, Shang-Fan Y, Kan D et al.: Variants of the antibody Herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610-1614 (2009). The longstanding held notion that one antibody equals one antigen and, hence, one function has been challenged in recent years. Improved technology in antibody production, especially the accumulation of sequence data of immunoglobulin genes and the advent of PCR have made it possible to clone antibody gene repertoires. The current paper provides further challenge to the notion of one antibody = one antigen by developing 'two-in-one' antibodies with an antigen-binding site that binds two distinct proteins with high affinity. A therapeutic variant antibody of Herceptin (Genentech, CA, USA) was isolated that binds the human EGF receptor (HER)2 and also to VEGF. This development may represent a breakthrough discovery and may have significant implications in the therapy of malignant, infectious, allergic and autoimmune disorders.