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Article ; Online: Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR.

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 32, Issue 2, Page(s) 556–558

Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.12.006
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Article ; Online: Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR.

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 7, Page(s) 2089–2104

Abstract: CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL ...

Abstract	CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL. However, CD19 loss is a frequent cause of relapse. Simultaneously targeting a second antigen, CD22, may decrease antigen escape, but is challenging: its density is approximately 10-fold less than CD19, and its large structure may hamper immune synapse formation. The characteristics of the optimal CD22 CAR are underexplored. We generated 12 distinct CD22 antibodies and tested CARs derived from them to identify a CAR based on the novel 9A8 antibody, which was sensitive to low CD22 density and lacked tonic signaling. We found no correlation between affinity or membrane proximity of recognition epitope within Ig domains 3-6 of CD22 with CART function. The optimal strategy for CD19/CD22 CART co-targeting is undetermined. Co-administration of CD19 and CD22 CARs is costly; single CARs targeting CD19 and CD22 are challenging to construct. The co-expression of two CARs has previously been achieved using bicistronic vectors. Here, we generated a dual CART product by co-transduction with 9A8-41BBζ and CAT-41BBζ (obe-cel), the previously described CD19 CAR. CAT/9A8 CART eliminated single- and double-positive target cells in vitro and eliminated CD19
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/metabolism ; T-Lymphocytes ; Neoplasm Recurrence, Local ; Burkitt Lymphoma ; Immunotherapy, Adoptive ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Antibodies ; Sialic Acid Binding Ig-like Lectin 2
Chemical Substances	Receptors, Chimeric Antigen ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Antibodies ; CD22 protein, human ; Sialic Acid Binding Ig-like Lectin 2
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.03.020
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Article ; Online: Genetic determinants of antimicrobial resistance in polymyxin B resistant Pseudomonas aeruginosa isolated from airways of patients with cystic fibrosis.

Simão, Felipe A / Almeida, Mila M / Rosa, Heloísa S / Marques, Elizabeth A / Leão, Robson S

Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology

2024

Abstract: ... identification, search for phages, and characterization of CF clones. All isolates in this study were polymyxin B ... B allowed us to understand the different mechanisms of resistance to antimicrobials, in addition ...

Abstract	Pseudomonas aeruginosa is the main pathogen associated with pulmonary exacerbation in patients with cystic fibrosis (CF). CF is a multisystemic genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, which mainly affects pulmonary function. P. aeruginosa isolated from individuals with CF in Brazil is not commonly associated with multidrug resistance (MDR), especially when compared to global occurrence, where the presence of epidemic clones, capable of expressing resistance to several drugs, is often reported. Due to the recent observations of MDR isolates of P. aeruginosa in our centers, combined with these characteristics, whole-genome sequencing was employed for analyses related to antimicrobial resistance, plasmid identification, search for phages, and characterization of CF clones. All isolates in this study were polymyxin B resistant, exhibiting diverse mutations and reduced susceptibility to carbapenems. Alterations in mexZ can result in the overexpression of the MexXY efflux pump. Mutations in oprD, pmrB, parS, gyrA and parC may confer reduced susceptibility to antimicrobials by affecting permeability, as observed in phenotypic tests. The phage findings led to the assumption of horizontal genetic transfer, implicating dissemination between P. aeruginosa isolates. New sequence types were described, and none of the isolates showed an association with epidemic CF clones. Analysis of the genetic context of P. aeruginosa resistance to polymyxin B allowed us to understand the different mechanisms of resistance to antimicrobials, in addition to subsidizing the understanding of possible relationships with epidemic strains that circulate among individuals with CF observed in other countries.
Language	English
Publishing date	2024-04-15
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2017175-4
ISSN	1678-4405 ; 1517-8382
ISSN (online)	1678-4405
ISSN	1517-8382
DOI	10.1007/s42770-024-01311-3
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Article ; Online: Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade.

Yam-Puc, Juan Carlos / Hosseini, Zhaleh / Horner, Emily C / Gerber, Pehuén Pereyra / Beristain-Covarrubias, Nonantzin / Hughes, Robert / Lulla, Aleksei / Rust, Maria / Boston, Rebecca / Ali, Magda / Fischer, Katrin / Simmons-Rosello, Edward / O'Reilly, Martin / Robson, Harry / Booth, Lucy H / Kahanawita, Lakmini / Correa-Noguera, Andrea / Favara, David / Ceron-Gutierrez, Lourdes /

Keller, Baerbel / Craxton, Andrew / Anderson, Georgina S F / Sun, Xiao-Ming / Elmer, Anne / Saunders, Caroline / Bermperi, Areti / Jose, Sherly / Kingston, Nathalie / Mulroney, Thomas E / Piñon, Lucia P G / Chapman, Michael A / Grigoriadou, Sofia / MacFarlane, Marion / Willis, Anne E / Patil, Kiran R / Spencer, Sarah / Staples, Emily / Warnatz, Klaus / Buckland, Matthew S / Hollfelder, Florian / Hyvönen, Marko / Döffinger, Rainer / Parkinson, Christine / Lear, Sara / Matheson, Nicholas J / Thaventhiran, James E D

Nature communications

2023 Volume 14, Issue 1, Page(s) 3292

Abstract: Age-associated B cells (ABC) accumulate with age and in individuals with different immunological ... frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising ...

Abstract	Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.
MeSH term(s)	Humans ; Immunity, Humoral ; Immune Checkpoint Inhibitors ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Vaccination ; Antigen-Antibody Complex ; Antibodies, Viral
Chemical Substances	Immune Checkpoint Inhibitors ; COVID-19 Vaccines ; Antigen-Antibody Complex ; Antibodies, Viral
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38810-0
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Article ; Online: The SARS-CoV-2 B.1.1.7 variant and increased clinical severity-the jury is out.

Giles, Benjamin / Meredith, Paul / Robson, Samuel / Smith, Gary / Chauhan, Anoop

The Lancet. Infectious diseases

2021 Volume 21, Issue 9, Page(s) 1213–1214

MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2
Language	English
Publishing date	2021-06-28
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00356-X
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Article ; Online: B-mode ultrasonography and ARFI elastography of articular and peri-articular structures of the hip joint in non-dysplastic and dysplastic dogs as confirmed by radiographic examination.

Carneiro, Rafael Kretzer / da Cruz, Igor Cezar Kniphoff / Gasser, Beatriz / Lima, Bruna / Aires, Luiz Paulo Nogueira / Ferreira, Márcio Poletto / Uscategui, Ricardo Andres Ramirez / Giglio, Robson Fortes / Minto, Bruno Watanabe / Rossi Feliciano, Marcus Antônio

BMC veterinary research

2023 Volume 19, Issue 1, Page(s) 181

Abstract: ... of B-mode ultrasonography and acoustic radiation force impulse (ARFI) elastography in assessing ... in some dysplastic dogs and an increase in the thickness of the joint capsule (cutoff value > 0.9 mm) in B-mode ... ultrasonography, were associated with a distraction index > 0.5, with both having a positive correlation. In B ...

Abstract	Background: Canine hip dysplasia is a common orthopedic disease in veterinary practice. The diagnosis is made by radiographic examinations that evaluate bone alterations associated with hip dysplasia. Although radiographic examination is the gold standard for diagnosis, it does not allow a detailed evaluation of soft tissues such as the joint capsule and periarticular muscles. This study aimed to evaluate the accuracy of B-mode ultrasonography and acoustic radiation force impulse (ARFI) elastography in assessing the joint capsule and periarticular muscles of dogs using the Orthopedic Foundation of Animals (OFA) classification and the distraction index (DI) in the early and late diagnosis of hip dysplasia. This study sought to propose a protocol for the ultrasonographic evaluation of the structures involved in canine hip dysplasia. Methods: Radiographic and ultrasonographic evaluations were performed on 108 hip joints of 54 dogs. Thirty dogs were older than 2 years and 24 were aged between 4 and 10 months. Results: It was verified that an increase in pectineus muscle stiffness (cutoff value > 2.77 m/s) by elastography in some dysplastic dogs and an increase in the thickness of the joint capsule (cutoff value > 0.9 mm) in B-mode ultrasonography, were associated with a distraction index > 0.5, with both having a positive correlation. In B-mode ultrasonographic evaluation, the presence of signs of degenerative joint disease, such as irregularities of the cranial edge of the acetabulum and femoral head, were associated with a distraction index > 0.5 in canines, with a specificity of 94%. In adult dogs, the findings of degenerative joint disease on ultrasound were associated with a diseased OFA classification (P < 0.05). Measurement of the joint capsule > 1.10 mm was diagnostic for dysplasia in unhealthy dogs by OFA. Conclusions: ARFI elastography has shown that the pectineus muscle may experience changes in stiffness in dysplastic animals. Additionally, changes in joint capsule thickness can be identified in B-mode in young and adult dogs with dysplastic joints, which contributes to the diagnosis of hip dysplasia.
MeSH term(s)	Animals ; Dogs ; Hip Dysplasia, Canine/diagnostic imaging ; Hip Dysplasia, Canine/complications ; Elasticity Imaging Techniques/veterinary ; Hip Dislocation/complications ; Hip Dislocation/veterinary ; Hip Joint/diagnostic imaging ; Ultrasonography/veterinary ; Dog Diseases/diagnostic imaging
Language	English
Publishing date	2023-10-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2191675-5
ISSN	1746-6148 ; 1746-6148
ISSN (online)	1746-6148
ISSN	1746-6148
DOI	10.1186/s12917-023-03753-7
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Article ; Online: Profile of T and B lymphocytes in individuals resistant to Schistosoma mansoni infection.

da Paixão de Souza, Robson / Araújo, Maria Ilma / Lopes, Diego Mota / Oliveira, Sérgio Costa / Fernandes, Jamille Souza / de Jesus, Kelvin Edson M / Carvalho, Edgar M / Oliveira, Ricardo Riccio / Cardoso, Luciana Santos

Parasitology research

2022 Volume 121, Issue 3, Page(s) 951–963

Abstract: ... through mechanisms associated with the Th2 response. Through flow cytometry, the phenotypic characterization of B and ...

Abstract	The mechanisms involved in the development of resistance to infection/reinfection by Schistosoma mansoni still arouse great interest and controversy. Some authors demonstrate that resistance to infection is attributed to a mixed Th1 and Th2 response and resistance to reinfection after repeated treatments through mechanisms associated with the Th2 response. Through flow cytometry, the phenotypic characterization of B and T lymphocytes in individuals residing in endemic areas with low parasite loads over 10 years was evaluated for the first time in humans. In this study, individuals with low parasite loads for Schistosoma mansoni had a higher proportion of Th1 and Th2 cells. In addition, lymphocytes from these individuals showed a higher degree of expression of costimulatory molecules CD28 and CTLA-4 and regulatory molecules FoxP3 and IL-10, when compared to individuals with high parasite loads. Our data indicate that the control of the parasite load of S. mansoni must be associated with a Th1, Th2, and regulatory response, and that further studies are needed to elucidate the possibility of mechanisms associated with the hyporesponsiveness of lymphocytes from individuals with high parasite loads.
MeSH term(s)	Animals ; B-Lymphocytes ; Humans ; Lymphocyte Count ; Schistosoma mansoni ; Schistosomiasis mansoni/parasitology ; Th2 Cells
Language	English
Publishing date	2022-02-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	284966-5
ISSN	1432-1955 ; 0932-0113 ; 0044-3255
ISSN (online)	1432-1955
ISSN	0932-0113 ; 0044-3255
DOI	10.1007/s00436-022-07435-5
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Article ; Online: Peptide fragments of bradykinin show unexpected biological activity not mediated by B

Souza-Silva, Igor Maciel / de Paula, Cristiane Amorim / Bolais-Ramos, Lucas / Santos, Anderson Kenedy / da Silva, Filipe Alex / de Oliveira, Vívian Louise Soares / da Rocha, Isabella Domingos / Antunes, Maísa Mota / Cordeiro, Lídia Pereira Barbosa / Teixeira, Vanessa Pereira / Scalzo Júnior, Sérgio Ricardo Aluotto / Raabe, Adriana Campezatto / Guimaraes, Pedro Pires Goulart / Amaral, Flávio Almeida / Resende, Jarbas Magalhães / Fontes, Marco Antônio Peliky / Menezes, Gustavo Batista / Guatimosim, Silvia / Santos, Robson Augusto Souza /

Verano-Braga, Thiago

British journal of pharmacology

2022 Volume 179, Issue 12, Page(s) 3061–3077

Abstract: ... 9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B: Conclusions and ... show biological activity, not mediated by B ...

Abstract	Background and purpose: Bradykinin (BK-(1-9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals. Experimental approach: BK peptides were quantified by MS in male rats. NO release was quantified from human, mouse and rat cells loaded with DAF-FM. Rat aortic rings were used to measure vascular reactivity. Changes in BP and HR were measured in conscious male rats. To evaluate pro-inflammatory effects both vascular permeability and nociception were measured in adult mice. Key results: BK-(1-7) and BK-(1-5) are produced in vivo from BK-(1-9). Both peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B Conclusions and implications: BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. BK-related peptide fragments show biological activity, not mediated by B
MeSH term(s)	Animals ; Bradykinin/pharmacology ; Male ; Mice ; Peptide Fragments ; Rats ; Receptor, Bradykinin B1 ; Receptor, Bradykinin B2 ; Receptors, Bradykinin/physiology
Chemical Substances	Peptide Fragments ; Receptor, Bradykinin B1 ; Receptor, Bradykinin B2 ; Receptors, Bradykinin ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2022-02-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15790
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Article ; Online: Long-term persistence of supernumerary B chromosomes in multiple species of Astyanax fish.

Silva, Duílio Mazzoni Zerbinato de Andrade / Ruiz-Ruano, Francisco J / Utsunomia, Ricardo / Martín-Peciña, María / Castro, Jonathan Pena / Freire, Paula Paccielli / Carvalho, Robson Francisco / Hashimoto, Diogo T / Suh, Alexander / Oliveira, Claudio / Porto-Foresti, Fábio / Artoni, Roberto Ferreira / Foresti, Fausto / Camacho, Juan Pedro M

BMC biology

2021 Volume 19, Issue 1, Page(s) 52

Abstract: Background: Eukaryote genomes frequently harbor supernumerary B chromosomes in addition ... to the "standard" A chromosome set. B chromosomes are thought to arise as byproducts of genome rearrangements and ... beyond species level has remained untested.: Results: Here we reveal that the large metacentric B chromosomes ...

Abstract	Background: Eukaryote genomes frequently harbor supernumerary B chromosomes in addition to the "standard" A chromosome set. B chromosomes are thought to arise as byproducts of genome rearrangements and have mostly been considered intraspecific oddities. However, their evolutionary transcendence beyond species level has remained untested. Results: Here we reveal that the large metacentric B chromosomes reported in several fish species of the genus Astyanax arose in a common ancestor at least 4 million years ago. We generated transcriptomes of A. scabripinnis and A. paranae 0B and 1B individuals and used these assemblies as a reference for mapping all gDNA and RNA libraries to quantify coverage differences between B-lacking and B-carrying genomes. We show that the B chromosomes of A. scabripinnis and A. paranae share 19 protein-coding genes, of which 14 and 11 were also present in the B chromosomes of A. bockmanni and A. fasciatus, respectively. Our search for B-specific single-nucleotide polymorphisms (SNPs) identified the presence of B-derived transcripts in B-carrying ovaries, 80% of which belonged to nobox, a gene involved in oogenesis regulation. Importantly, the B chromosome nobox paralog is expressed > 30× more than the A chromosome paralog. This indicates that the normal regulation of this gene is altered in B-carrying females, which could potentially facilitate B inheritance at higher rates than Mendelian law prediction. Conclusions: Taken together, our results demonstrate the long-term survival of B chromosomes despite their lack of regular pairing and segregation during meiosis and that they can endure episodes of population divergence leading to species formation.
MeSH term(s)	Animals ; Characidae/genetics ; Chromosome Mapping ; Chromosomes/genetics ; Female ; Genome ; Male ; Polymorphism, Single Nucleotide ; Species Specificity
Language	English
Publishing date	2021-03-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-021-00991-9
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Article ; Online: Human marginal zone B cell development from early T2 progenitors.

The Journal of experimental medicine

2021 Volume 218, Issue 4

Abstract: B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2 ... and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation ... with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is ...

Abstract	B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.
MeSH term(s)	Adult ; Aged ; Blood Donors ; Case-Control Studies ; Cell Differentiation/immunology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Cells, Cultured ; Female ; Gastrointestinal Tract/immunology ; Humans ; Immunoglobulin M/metabolism ; Integrin beta Chains/metabolism ; Interleukin-4 Receptor alpha Subunit/metabolism ; Lupus Nephritis/blood ; Lupus Nephritis/immunology ; Lupus Nephritis/pathology ; Lymphoid Tissue/immunology ; Male ; Middle Aged ; Phenotype ; Precursor Cells, B-Lymphoid/immunology ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcriptome ; Young Adult
Chemical Substances	IL4R protein, human ; Immunoglobulin M ; Integrin beta Chains ; Interleukin-4 Receptor alpha Subunit
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20202001
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