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Anti-Topoisomerase I Antibody

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1. RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis. Full Text available with Trip Pro

RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis. Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. To elucidate major histocompatibility complex-linked systemic sclerosis genetics, we performed genotyping of major histocompatibility (...) complex-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed two major histocompatibility complex haplotypes associated with systemic sclerosis. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in RXRB as a susceptibility variant (P = 1.3 × 10-15; odds ratio [OR] = 9.4) with amino acid substitution p.V95A on the risk haplotype

2017 Journal of Investigative Dermatology

2. Anti-Topoisomerase I Antibody

Anti-Topoisomerase I Antibody Anti-Topoisomerase I Antibody Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Anti-Topoisomerase I (...) Antibody Anti-Topoisomerase I Antibody Aka: Anti-Topoisomerase I Antibody , Anti-Topoisomerase1 Antibody , Anti-Scl-70 Antibody , Anti-Topoisomerase I , Topoisomerase 1 Antibody , Anti-DNA-Topoisomerase I , Anti-Scl-70 II. Causes: Negative Normal III. Causes: Positive (Percentage refers to sensitivity) (20-30% sensitivity) Anti-Scl-70 is highly specific for Implies a poor prognosis Associated with renal involvement IV. References Gladman in Klippel (1997) Rheumatic Diseases p. 255-6 Peng in Ruddy (2001

2018 FP Notebook

3. Novel Autoimmune IgM Antibody Attenuates Atherosclerosis in IgM Deficient Low-Fat Diet-Fed, but Not Western Diet-Fed <i>Apoe</i><sup>-/-</sup> Mice. (Abstract)

Novel Autoimmune IgM Antibody Attenuates Atherosclerosis in IgM Deficient Low-Fat Diet-Fed, but Not Western Diet-Fed <i>Apoei>-/- Mice. Oxidized phospholipids (OxPL), such as the oxidized derivatives of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine, have been shown to be the principal biologically active components of minimally oxidized LDL (low (...) -density lipoprotein). The role of OxPL in cardiovascular diseases is well recognized, including activation of inflammation within vascular cells. Atherosclerotic Apoe-/- mice fed a high-fat diet develop antibodies to OxPL, and hybridoma B-cell lines producing natural anti-OxPL autoantibodies have been successfully generated and characterized. However, as yet, no studies have been reported demonstrating that treatment with OxPL neutralizing antibodies can be used to prevent or reverse advanced

2020 Thrombosis and Vascular Biology

4. Antiphospholipid Antibodies to Domain I of Beta-2-Glycoprotein I Show Different Subclass Predominance in Comparison to Antibodies to Whole Beta-2-glycoprotein I Full Text available with Trip Pro

Antiphospholipid Antibodies to Domain I of Beta-2-Glycoprotein I Show Different Subclass Predominance in Comparison to Antibodies to Whole Beta-2-glycoprotein I Antiphospholipid antibodies (aPL), the serological hallmark of antiphospholipid syndrome (APS), are a heterogeneous group of autoantibodies raised against circulating blood proteins. Of these proteins, the phospholipid-binding b2-glycoprotein I (β2GPI) is considered to be the main autoantigen in APS. Indeed, IgG antibodies targeting (...) b2GPI (ab2GPI) directly cause both thrombosis and pregnancy morbidity in several mouse models. While antibodies raised against all five domains of b2GPI have been reported, a subgroup of IgG ab2GPI raised against the first domain (DI) of b2GPI (aDI), strongly correlate with thrombotic APS, and drive thrombosis and pregnancy loss in vivo. Few studies have focused on determining the type of IgG subclass(es) for aPL. The subclass of an antibody is important as this dictates the potential activity

2018 Frontiers in immunology

5. Detection of Immunoglobulin G Antibodies to <i>Taenia solium</i> Cysticercosis Antigen Glutathione-<i>S</i>-Transferase-rT24H in Malian Children Using Multiplex Bead Assay. Full Text available with Trip Pro

Detection of Immunoglobulin G Antibodies to <i>Taenia soliumi> Cysticercosis Antigen Glutathione-<i>Si>-Transferase-rT24H in Malian Children Using Multiplex Bead Assay. Blood samples from 805 students attending 42 elementary schools in Mopti, Sikasso, and Koulikoro regions, and Bamako district in Mali participated in a school water, sanitation, and hygiene intervention. Immunoglobulin (Ig) G responses to several antigens/pathogens were assessed by a multiplex bead assay (MBA

2018 American Journal of Tropical Medicine & Hygiene

6. Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas Full Text available with Trip Pro

Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas Changes in glycosylation of the constant domain (Fc) of monoclonal antibodies (mAbs) enhance antibody-dependent cell-mediated cytotoxicity independently of downstream effects following receptor blockade by the antibody, thus extending their indication. We investigated the safety, pharmacokinetics, pharmacodynamics and antitumour activity (...) of tomuzotuximab, an IgG1 glycoengineered mAb against the epidermal growth factor receptor with enhanced tumour cytotoxicity in a phase I dose-escalation study (NTC01222637).Forty-one patients with advanced solid tumours refractory to standard therapies received tomuzotuximab weekly (12-1370 mg) or two-weekly (990 mg) on a three-plus-three dose escalation design.A maximum tolerated dose was not reached. The most frequent treatment-related adverse events were infusion-related reactions in 31 (76%) patients

2018 ESMO open

7. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours Full Text available with Trip Pro

Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies

2018 ESMO open

8. Safety and Differential Antibody and T-Cell Responses to <i>Plasmodium falciparum</i> Sporozoite Vaccine by Age in Tanzanian Adults, Adolescents, Children, and Infants. Full Text available with Trip Pro

Safety and Differential Antibody and T-Cell Responses to <i>Plasmodium falciparumi> Sporozoite Vaccine by Age in Tanzanian Adults, Adolescents, Children, and Infants. In 2016, there were more cases and deaths caused by malaria globally than in 2015. An effective vaccine would be an ideal additional tool for reducing malaria's impact. Sanaria® PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) has been well tolerated (...) dosage regimens. Because all age groups received three doses of 9.0 × 105 PfSPZ of PfSPZ Vaccine, immune responses were compared at this dosage. Median antibody responses against Pf circumsporozoite protein and PfSPZ were highest in infants and lowest in adults. T-cell responses were highest in 6-10-year olds after one dose and 1-5-year olds after three doses; infants had no significant positive T-cell responses. The safety data were used to support initiation of trials in > 300 infants in Kenya

2019 American Journal of Tropical Medicine & Hygiene Controlled trial quality: predicted high

9. Bayesian Evaluation of Three Serological Tests for Detecting Antibodies against <i>Brucella</i> spp. among Humans in the Northwestern Part of Ecuador. (Abstract)

Bayesian Evaluation of Three Serological Tests for Detecting Antibodies against <i>Brucellai> spp. among Humans in the Northwestern Part of Ecuador. Brucellosis is an important but neglected zoonosis that causes serious economic losses both in livestock and human populations. The aim of the present study was to estimate the true prevalence of brucellosis together with diagnostic sensitivity and specificity of three serological tests in humans of the northwestern part of Ecuador using

2019 American Journal of Tropical Medicine & Hygiene

10. HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes. (Abstract)

HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes. Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-HLA antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody binding (...) patterns and introduce genetic engineering of SLA epitopes.Sensitized patient sera was grouped by calculated panel reactive antibody (cPRA) and luminex single antigen reactivity profile and was tested with cloned GGTA1/CMAH/B4GalNT2 glycan knockout (KO) porcine cells. Pig reactivity was assessed by direct flow cytometric crossmatch (FCXM) and studied following elution from pig cells. To study antigenicity of individual Class I HLA and SLA alleles in cells, irrelevant sera binding to lymphoblastoid

2019 Transplantation

11. Efficacy of a multimechanistic monoclonal antibody combination against <i>Staphylococcus aureus</i> surgical site infections in mice. Full Text available with Trip Pro

Efficacy of a multimechanistic monoclonal antibody combination against <i>Staphylococcus aureusi> surgical site infections in mice. Surgical site infections (SSI) are commonly caused by Staphylococcus aureus Here, we report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus α-toxin, clumping factor A and four leukocidins (LukSF, LukED, HlgAB and HlgCB) plus vancomycin had enhanced efficacy than control antibody plus vancomycin in two mouse models of S

2019 Antimicrobial Agents and Chemotherapy

12. Penetration of a Monoclonal Antibody Combination (ASN100) Targeting <i>S. aureus</i> Cytotoxins in Lung Epithelial Lining Fluid: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers. Full Text available with Trip Pro

Penetration of a Monoclonal Antibody Combination (ASN100) Targeting <i>S. aureusi> Cytotoxins in Lung Epithelial Lining Fluid: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers. ASN100 is a novel antibody combination of two fully human IgG1 kappa monoclonal antibodies, ASN-1 and ASN-2 which neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five bi-component leukocidins. We assessed the safety, tolerability, and serum (...) to the Investigational Product. ASN100 exhibited linear serum PK with a half-life of approximately three weeks and showed detectable penetration into the ELF. No treatment-emergent anti-drug antibody responses were detected. The toxin neutralizing potency of ASN100 in human serum was confirmed up to 58 days post-dosing.The favorable safety profile, ELF penetration, and maintained functional activity in serum supported the further clinical development of ASN100.Copyright © 2019 Magyarics et al.

2019 Antimicrobial Agents and Chemotherapy Controlled trial quality: uncertain

13. Development of an Antigen Detection ELISA for Bancroftian Filariasis Using <i>Bm</i>SXP-Specific Recombinant Monoclonal Antibody. (Abstract)

Development of an Antigen Detection ELISA for Bancroftian Filariasis Using <i>Bmi>SXP-Specific Recombinant Monoclonal Antibody. Lymphatic filariasis is a mosquito-borne parasitic disease responsible for morbidity and disability that affects 1.2 billion people worldwide, mainly the poor communities. Currently, filarial antigen testing is the method of choice for the detection of bancroftian filariasis, and to date, there are two commonly used tests. In the present study, a recently reported (...) recombinant monoclonal antibody (5B) specific to BmSXP filarial antigen was used in developing an ELISA for the detection of circulating filarial antigen in sera of patients with bancroftian filariasis. The performance of the ELISA was evaluated using 124 serum samples. The ELISA was positive with all sera from microfilaremic bancroftian filariasis patients (n = 34). It also showed 100% diagnostic specificity when tested with sera from 50 healthy individuals and 40 patients with other parasitic diseases

2019 American Journal of Tropical Medicine & Hygiene

14. Case Report: Disseminated <i>Mycobacterium kansasii</i> Disease in a Patient with Anti-IFN-Gamma Antibody. (Abstract)

Case Report: Disseminated <i>Mycobacterium kansasiii> Disease in a Patient with Anti-IFN-Gamma Antibody. Disseminated nontuberculous mycobacterial (NTM) infections usually occur in severely immunosuppressed patients. These infections may also occur in previously immunocompetent patients with acquired anti-IFN-gamma antibodies (anti-IFN-γ Abs). A previously healthy 33-year-old man presented with a 3-week history of cough and fever. Chest computed tomography showed air-space consolidation (...) an increased titer. Antimycobacterial drug treatments were initiated after diagnosis. His symptoms improved over 2 months, and he remains well on outpatient management. Disseminated M. kansasii disease is a very rare condition suggestive of immunosuppression. Testing for anti-IFN-γ antibodies might be important in all cases of disseminated M. kansasii disease.

2019 American Journal of Tropical Medicine & Hygiene

15. Antibody Responses to <i>Fusobacterium nucleatum</i> Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer. (Abstract)

Antibody Responses to <i>Fusobacterium nucleatumi> Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer. There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition (...) and Cancer (EPIC) cohort.We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any

2019 Cancer Epidemiology & Biomarkers and Prevention

16. Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and <i>H. pylori</i> and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China. (Abstract)

Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and <i>H. pylorii> and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China. Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia.A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 (...) GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders.There was an average interval of 8 years between baseline blood draw

2019 Cancer Epidemiology & Biomarkers and Prevention

17. Immunoglobulin-like Domain of <i>Hs</i>FcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies. Full Text available with Trip Pro

Immunoglobulin-like Domain of <i>Hsi>FcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies. The cellular surface molecule HsTOSO/FAIM3/HsFcμR has been identified as an IgM-specific Fc receptor expressed on lymphocytes. Here, we show that its extracellular immunoglobulin-like domain (HsFcμR-Igl) specifically binds to IgM/antigen immune complexes (ICs) and exploit this property for the development of novel detection systems (...) for IgM antibodies directed against Crimean-Congo hemorrhagic fever virus (CCHFV) and Zika virus (ZIKV).His-tagged HsFcμR-Igl was expressed in Escherichia coli and purified by affinity chromatography, oxidative refolding, and size-exclusion chromatography. Specific binding of HsFcμR-Igl to IgM/antigen ICs was confirmed, and 2 prototypic ELISAs for the detection of anti-CCHFV and anti-ZIKV IgM antibodies were developed. Thereby, patient sera and virus-specific recombinant antigens directly labeled

2019 Clinical Chemistry

18. A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-<i>Staphylococcus aureus</i> THIOMAB™ antibody-antibiotic conjugate, in healthy volunteers. Full Text available with Trip Pro

A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-<i>Staphylococcus aureusi> THIOMAB™ antibody-antibiotic conjugate, in healthy volunteers. BACKGROUND:Staphylococcus aureus causes serious bacterial infections with high morbidity and mortality, necessitating the discovery of new antibiotics. DSTA4637S is a novel antibody-antibiotic conjugate designed to target intracellular S. aureus not adequately eliminated (...) meaningful or dose-related changes in laboratory parameters or vital signs occurred. Pharmacokinetics of plasma DSTA4637S conjugate and serum DSTA4637S total antibody was dose proportional. Systemic exposure of unconjugated dmDNA31 was low. No DSTA4637S-induced anti-drug antibody responses were observed.CONCLUSIONS: DSTA4637S was generally safe and well tolerated as a single i.v. dose in healthy volunteers. DSTA4637S has a favorable safety and pharmacokinetic profile that supports future development

2019 Antimicrobial Agents and Chemotherapy Controlled trial quality: uncertain

19. Detection of anti-domain I antibodies by chemiluminescence enables the identification of high-risk antiphospholipid syndrome patients: A multicenter multiplatform study. (Abstract)

Detection of anti-domain I antibodies by chemiluminescence enables the identification of high-risk antiphospholipid syndrome patients: A multicenter multiplatform study. Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-β2glycoprotein I (β2GPI) proved to be pathogenic, but are not included in the current classification criteria.Investigate the clinical value of detecting (...) anti-DI IgG in APS.From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-β2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® β2GPI domain I assay.Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-β2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG

2020 Journal of Thrombosis and Haemostasis

20. First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. Full Text available with Trip Pro

First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed

2020 Clinical Cancer Research

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