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1.
Nucleic Acids Res ; 52(D1): D1062-D1071, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38000392

RESUMO

The SysteMHC Atlas v1.0 was the first public repository dedicated to mass spectrometry-based immunopeptidomics. Here we introduce a newly released version of the SysteMHC Atlas v2.0 (https://systemhc.sjtu.edu.cn), a comprehensive collection of 7190 MS files from 303 allotypes. We extended and optimized a computational pipeline that allows the identification of MHC-bound peptides carrying on unexpected post-translational modifications (PTMs), thereby resulting in 471K modified peptides identified over 60 distinct PTM types. In total, we identified approximately 1.0 million and 1.1 million unique peptides for MHC class I and class II immunopeptidomes, respectively, indicating a 6.8-fold increase and a 28-fold increase to those in v1.0. The SysteMHC Atlas v2.0 introduces several new features, including the inclusion of non-UniProt peptides, and the incorporation of several novel computational tools for FDR estimation, binding affinity prediction and motif deconvolution. Additionally, we enhanced the user interface, upgraded website framework, and provided external links to other resources related. Finally, we built and provided various spectral libraries as community resources for data mining and future immunopeptidomic and proteomic analysis. We believe that the SysteMHC Atlas v2.0 is a unique resource to provide key insights to the immunology and proteomics community and will accelerate the development of vaccines and immunotherapies.


Assuntos
Bases de Dados de Proteínas , Peptídeos , Proteômica , Espectrometria de Massas , Peptídeos/química , Peptídeos/imunologia , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Bases de Dados de Proteínas/normas , Internet , Humanos , Animais
2.
Mol Cell Proteomics ; 22(10): 100645, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37709257

RESUMO

We present an integrated immunopeptidomics and proteomics study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to comprehensively decipher the changes in host cells in response to viral infection. Immunopeptidomics analysis identified viral antigens presented by host cells through both class I and class II MHC system for recognition by the adaptive immune system. The host proteome changes were characterized by quantitative proteomics and glycoproteomics and from these data, the activation of toll-like receptor 3-interferon pathway was identified. Glycosylation analysis of human leukocyte antigen (HLA) proteins from the elution and flow-through of immunoprecipitation revealed that SARS-CoV-2 infection changed the glycosylation pattern of certain HLA alleles with different HLA alleles, showing distinct dynamic changes in relative abundance. The difference in the glycosylation and abundance of HLA alleles changed the number of strong binding antigens each allele presented, suggesting the impact of SARS-CoV-2 infection on antigen presentation is allele-specific. These results could be further exploited to explain the imbalanced response from innate and adaptive immune system in coronavirus disease 2019 cases, which would be helpful for the development of therapeutics and vaccine for coronavirus disease 2019 and preparation for future pandemic.

3.
Cell Rep Methods ; 3(6): 100511, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37426761

RESUMO

The identification of tumor-specific antigens (TSAs) is critical for developing effective cancer immunotherapies. Mass spectrometry (MS)-based immunopeptidomics has emerged as a powerful tool for identifying TSAs as physical molecules. However, current immunopeptidomics platforms face challenges in measuring low-abundance TSAs in a precise, sensitive, and reproducible manner from small needle-tissue biopsies (<1 mg). Inspired by recent advances in single-cell proteomics, microfluidics technology offers a promising solution to these limitations by providing improved isolation of human leukocyte antigen (HLA)-associated peptides with higher sensitivity. In this context, we highlight the challenges in sample preparation and the rationale for developing microfluidics technology in immunopeptidomics. Additionally, we provide an overview of promising microfluidic methods, including microchip pillar arrays, valved-based systems, droplet microfluidics, and digital microfluidics, and discuss the latest research on their application in MS-based immunopeptidomics and single-cell proteomics.


Assuntos
Microfluídica , Neoplasias , Humanos , Espectrometria de Massas/métodos , Antígenos de Histocompatibilidade Classe I , Antígenos HLA , Antígenos de Neoplasias
4.
Semin Immunol ; 69: 101798, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37348326
5.
Cancer Discov ; 13(2): 410-431, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36302218

RESUMO

Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DC) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of senescence-associated self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong antitumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent antitumor immune responses. SIGNIFICANCE: Our study shows that senescent cells are endowed with a high immunogenic potential-superior to the gold standard of immunogenic cell death. We harness these properties of senescent cells to trigger efficient and protective CD8-dependent antitumor immune responses. See related article by Chen et al., p. 432. This article is highlighted in the In This Issue feature, p. 247.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Camundongos , Animais , Humanos , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos/imunologia , Senescência Celular , Microambiente Tumoral
6.
Arthrosc Sports Med Rehabil ; 4(6): e1941-e1951, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36579042

RESUMO

Purpose: To analyze the rates of graft ruptures and growth disorders, the level of return to sport, and the clinical results of 2 lateral extra-articular procedures in growing children. Methods: This study was a retrospective, single-center study of patients undergoing anterior cruciate ligament (ACL) surgery combined with 2 different lateral extra-articular procedures (anatomic reconstruction with a gracilis graft or modified Lemaire technique with a strip of fascia lata). The measurements of side-to-side anterior laxity and pivot shift were performed preoperatively and at the last follow-up. The sports level and the complications rate were assessed. The minimal clinically important differences (MCID) and patient acceptable symptoms state threshold scores were calculated. Results: Thirty-nine patients (40 ACLs) were included (20 anatomic and 20 modified Lemaire) at an average follow-up of 57 months ± 10 [42-74]. One patient (2.5%) was lost to follow-up. The mean age at surgery was 13.8 ± 1.4 years old [9.8; 16.5]. One graft failure was reported (2.6% [0.06-13.5]) at 35.6 months after surgery. Two cases (5.4%) of femoral overgrowth were observed, and one of them required distal femoral epiphysiodesis. Ninety-two percent of the patients returned to sports. At the final follow-up, side-to-side anterior laxity was significantly improved, and no residual pivot shift was recorded in 95% of patients. Eighty-nine percent of the patients presented a Pedi-International Knee Documentation Committee score greater than the MCID postoperatively, and 77% presented a Lysholm score greater than the MCID. Conclusions: This series of ACL reconstructions combined with 2 different lateral extra-articular procedures in skeletally immature patients demonstrated promising findings. The low rate of observed complications, including graft rupture and growth disturbance, is encouraging, but the small study population and lack of comparative group precludes reliable conclusions. Level of Evidence: IV, therapeutic case series.

7.
Front Med (Lausanne) ; 9: 826746, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265640

RESUMO

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.

8.
iScience ; 25(2): 103768, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35141507

RESUMO

Understanding the molecular principles that govern the composition of the MHC-I immunopeptidome across different primary tissues is fundamentally important to predict how T cells respond in different contexts in vivo. Here, we performed a global analysis of the MHC-I immunopeptidome from 29 to 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, HLA-B, and HLA-C allotypes do not contribute evenly to the global composition of the MHC-I immunopeptidome across multiple human tissues. Second, we found that tissue-specific and housekeeping MHC-I peptides share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-I immunopeptidome at the organism-wide scale. Fourth, we uncovered new components of the antigen processing and presentation network, including the carboxypeptidases CPE, CNDP1/2, and CPVL. Together, this study opens up new avenues toward a system-wide understanding of antigen presentation in vivo across mammalian species.

9.
Cell Syst ; 13(2): 143-157.e3, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34637888

RESUMO

The rapid, global dispersion of SARS-CoV-2 has led to the emergence of a diverse range of variants. Here, we describe how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic. We analyzed a total of 330,246 high-quality SARS-CoV-2 genome assemblies, sampled across 143 countries and all major continents from December 2019 to December 2020 before mass vaccination or the rise of the Delta variant. We observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family; this is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7-supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic.


Assuntos
COVID-19 , Epitopos de Linfócito T , SARS-CoV-2 , COVID-19/virologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Mutação , SARS-CoV-2/genética
10.
Methods Mol Biol ; 2420: 137-147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34905171

RESUMO

Developing a deep and comprehensive understanding of the collection of peptides presented by class I human leukocyte antigens (HLA ), collectively referred to as the immunopeptidome , is conducive to the success of a wide range of immunotherapies. The development of tools that enable the deconvolution of immunopeptidomes in the context of disease can help improve the specificity and effectiveness of therapeutic strategies targeting these peptides, such as adoptive T-cell therapy and vaccines. Here, we describe a computational workflow that facilitates the processing and interpretation of data-independent acquisition mass spectrometry (DIA-MS). We consider a specific variation of DIA-MS known as SWATH-MS. SWATH-MS is a promising technique that can be utilized to reproducibly characterize and quantify immunopeptidomes isolated from a wide range of biological sources. In this workflow, we use an assortment of database search engines and computational tools to build high-quality HLA allele-specific peptide spectral peptide libraries for the analysis of immunopeptidomic datasets acquired by SWATH-MS. Generating and sharing these spectral libraries are essential for the SWATH-MS technology to meet its full potential and to enable the rapid and reproducible quantification of HLA-specific peptides across multiple samples.


Assuntos
Espectrometria de Massas , Alelos , Antígenos HLA , Humanos , Biblioteca de Peptídeos , Peptídeos , Proteoma , Proteômica
11.
Mol Cell Proteomics ; 21(1): 100178, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798331

RESUMO

MS-based immunopeptidomics is maturing into an automatized and high-throughput technology, producing small- to large-scale datasets of clinically relevant major histocompatibility complex (MHC) class I-associated and class II-associated peptides. Consequently, the development of quality control (QC) and quality assurance systems capable of detecting sample and/or measurement issues is important for instrument operators and scientists in charge of downstream data interpretation. Here, we created MhcVizPipe (MVP), a semiautomated QC software tool that enables rapid and simultaneous assessment of multiple MHC class I and II immunopeptidomic datasets generated by MS, including datasets generated from large sample cohorts. In essence, MVP provides a rapid and consolidated view of sample quality, composition, and MHC specificity to greatly accelerate the "pass-fail" QC decision-making process toward data interpretation. MVP parallelizes the use of well-established immunopeptidomic algorithms (NetMHCpan, NetMHCIIpan, and GibbsCluster) and rapidly generates organized and easy-to-understand reports in HTML format. The reports are fully portable and can be viewed on any computer with a modern web browser. MVP is intuitive to use and will find utility in any specialized immunopeptidomic laboratory and proteomics core facility that provides immunopeptidomic services to the community.


Assuntos
Antígenos de Histocompatibilidade Classe I , Software , Peptídeos , Proteômica , Controle de Qualidade
12.
J Vis Exp ; (176)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723952

RESUMO

Immunopeptidomics is an emerging field that fuels and guides the development of vaccines and immunotherapies. More specifically, it refers to the science of investigating the composition of peptides presented by major histocompatibility complex (MHC) class I and class II molecules using mass spectrometry (MS) technology platforms. Among all the steps in an MS-based immunopeptidomics workflow, sample preparation is critically important for capturing high-quality data of therapeutic relevance. Here, step-by-step instructions are described to isolate MHC class I and II-associated peptides by immunoaffinity purification from quality control samples, from mouse (EL4 and A20), and human (JY) cell lines more specifically. The various reagents and specific antibodies are thoroughly described to isolate MHC-associated peptides from these cell lines, including the steps to verify the beads-binding efficiency of the antibody and the elution efficiency of the MHC-peptide complexes from the beads. The protocol can be used to establish and standardize an immunopeptidomics workflow, as well as to benchmark new protocols. Moreover, the protocol represents a great starting point for any non-experts in addition to foster the intra- and inter-laboratory reproducibility of the sample preparation procedure in immunopeptidomics.


Assuntos
Antígenos de Histocompatibilidade Classe I , Peptídeos , Antígenos HLA , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Espectrometria de Massas/métodos , Peptídeos/análise , Reprodutibilidade dos Testes
13.
STAR Protoc ; 2(4): 100875, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34746858

RESUMO

Identification of proteasomal spliced peptides (PSPs) by mass spectrometry (MS) is not possible with traditional search engines. Here, we provide a protocol for running RHybridFinder (RHF), an R package for the computational inference of putative PSPs detected by MS. RHF extracts high confidence scored de novo sequenced peptides identified by PEAKS software. Those peptides are then matched to protein databases to infer cis- or trans-spliced major histocompatibility complex (MHC)-associated peptides. RHF is relatively fast and straightforward. PSPs have to be validated experimentally. For complete details on the use and execution of the original protocol, please refer to Faridi et al. (2018).


Assuntos
Peptídeos , Complexo de Endopeptidases do Proteassoma , Proteômica/métodos , Software , Bases de Dados de Proteínas , Epitopos/genética , Humanos , Espectrometria de Massas , Peptídeos/química , Peptídeos/genética , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/genética
14.
Orthop Traumatol Surg Res ; 107(3): 102875, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33652151

RESUMO

INTRODUCTION: Hinged total knee arthroplasty (TKA) implants are a commonly used option during revision or even primary surgery, but their complications are not as well known, due to the rapid adoption of gliding implants. The literature is inconsistent on this topic, with studies having a small sample size, varied follow-up duration and very different indications. This led us to carry out a large multicentre study with a minimum follow-up of 5 years to evaluate the complications after hinged TKA in a non-tumoral context based on the indications of primary arthroplasty, aseptic surgical revision or fracture treatment around the knee. HYPOTHESIS: Hinged TKA was associated with a high complication rate, no matter the indication. MATERIAL AND METHODS: Two hundred and ninety patients (290 knees) were included retrospectively between January 2006 and December 2011 at 17 sites, with a minimum follow-up of 5 years. The patients were separated into three groups: primary surgery (111 patients), aseptic revision surgery (127 patients) and surgery following a recent (<3 months) fracture (52 patients: 13 around the TKA and 39 around the knee treated by hinged TKA). Patients who had an active infection the knee of interest were excluded. All the patients were reviewed based on a standardised computer questionnaire validated by the SOFCOT. RESULTS: The mean follow-up was 71±39 months [range, 0 to 188]. Of the 290 patients included in the study, 108 patients (37%) suffered at least one complication and 55 patients (19%) had to undergo revision surgery: 16 in the primary TKA group (16/111, 14% of primary TKA), 28 in the revision surgery group (28/127, 22% of revision TKA) and 11 in the fracture treatment group (11/52, 21% of fracture TKA). The complications due to the hinged TKA for the entire cohort from most to least common were stiffness (41/290, 14%), chronic postoperative pain (37/290, 13%), infection (32/290, 11%), aseptic loosening (23/290, 8%), general complications (20/290, 7%), extensor mechanism complications (19/290, 6%), periprosthetic fracture (9/290, 3%), mechanical failure (2/290, 0.7%). In the primary TKA group, the main complication leading to re-operation was infection (12/111, 11%), while it was loosening for the revision TKA group (15/127, 12%) and infection (8/52, 15%) for the fracture TKA group. DISCUSSION: The 37% complication rate for hinged TKA implants is high, with 19% of them requiring re-operation. The frequency of complications differed depending on the context in which the hinged implant was used (primary, revision, fracture). The complications requiring revision surgery were major ones that prevented patients from preserving their autonomy (infection, symptomatic loosening, fracture, implant failure). The most found complications - stiffness and chronic pain - rarely led to revision. LEVEL OF EVIDENCE: IV; retrospective cohort study.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Estudos Multicêntricos como Assunto , Falha de Prótese , Reoperação , Estudos Retrospectivos
15.
Arthroscopy ; 37(8): 2465-2472, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33631252

RESUMO

PURPOSE: The purpose of this study was to evaluate and compare the functional outcomes after endoscopic repair of partial or full-thickness gluteus medius tears at a minimum 2 years' follow-up. METHODS: Patients with isolated tears of the gluteus medius tendon repaired endoscopically between 2012 and 2017 were evaluated at a minimum 2 years of follow-up. Patients with large, retracted and/or irreducible tears, advanced atrophy, or fatty degeneration or with concomitant other hip pathology were excluded. Functional outcomes were assessed using the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and visual analog scale (VAS) for pain preoperatively and at the last follow-up RESULTS: Forty-six patients, 3 men and 43 women with a mean (SD) age of 63 (9; range, 43-82) years, were included. Thirty-three patients (72%) had partial-thickness tears and 13 (28%) had full-thickness tears. Pain was reduced significantly from a median of 8 (IQR: 6-8) at the preoperative visit to a median of 2 (IQR: 15) at the most recent follow-up (P < .0001). The mHHS and NAHS improved significantly from a median of 44 (IQR: 35-52) to 80 (IQR: 64-87) (P < .0001) and 52 (IQR: 43-56) to 75 (IQR: 66-94) (P < .0001), respectively. These improvements were clinically relevant and surpass the reported minimal clinically important difference. Patients with partial tears had significant functional gains in the mHHS in comparison with patients with full-thickness tears (P = .02). No other statistically significant difference between groups of tear grade was observed. CONCLUSIONS: Endoscopic repair of gluteus medius tendon tears yields excellent functional outcomes at a minimum follow-up of 2 years. A lower functional improvement for full-thickness tears was observed; this difference was statistically significant for 1 of the 2 scores evaluated. LEVEL OF EVIDENCE: Level III, retrospective comparative cohort.


Assuntos
Traumatismos dos Tendões , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Resultado do Tratamento
16.
Methods Mol Biol ; 2120: 173-181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32124319

RESUMO

Mass spectrometry has emerged as the method of choice for the exploration of the immunopeptidome. Insights from the immunopeptidome promise novel cancer therapeutic approaches and a better understanding of the basic mechanisms of our immune system. To meet the computational demands from the steady gain in popularity and reach of mass spectrometry-based immunopeptidomics analysis, we created the SysteMHC Atlas project, a first-of-its-kind computational pipeline and resource repository dedicated to standardizing data analysis and public dissemination of immunopeptidomic datasets.


Assuntos
Antígenos HLA , Complexo Principal de Histocompatibilidade , Espectrometria de Massas/métodos , Proteômica/métodos , Alelos , Antígenos HLA/química , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Internet , Neoplasias/genética , Neoplasias/imunologia , Software
17.
Orthop Traumatol Surg Res ; 106(3): 519-525, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32029409

RESUMO

INTRODUCTION: Sometimes the slightest changes in implant design can lead to failure, even for a validated prosthesis. A minimally invasive cementless model, the SL-PLUS MIA™, in which the lateral shoulder is eliminated, was developed from the Zweymüller SL-PLUS™ implant. After satisfactory in-vitro tests, it required in-vivo assessment to ensure that bone fixation is good. We therefore conducted a prospective randomized study comparing the two versions of the Zweymüller femoral stem, with the aim of (1) comparing bone fixation up to 2 years' follow-up on EBRA-FCA radiography; and (2) assessing any difference in clinical or radiographic performance. HYPOTHESIS: Primary stability assessed on EBRA-FCA does not significantly differ between the SL-PLUS MIA™ and SL-PLUS™ implants. PATIENTS AND METHOD: A single-center multi-surgeon prospective randomized study included 80 patients (79 were operated on) between April 2009 and October 2012, with a mean 6 years' follow-up. Radiographic assessment used the EBRA-FCA application up to 2 years' follow-up; clinical assessment, with a minimum 5 years' follow-up, was performed by a single observer, using the Harris and Oxford-12 scores. The two groups, SL-PLUS™ (n=38) and SL-PLUS MIA™ (n=41), were comparable in gender, age, indications, body-mass index and preoperative functional status. RESULTS: At a minimum 2 years' follow-up, 24 SL-PLUS™ and 27 SL-PLUS MIA™ implants were analyzed on EBRA-FCA. Mean migration was respectively -0.3mm±0.8 [range, -1.6 to 1.3] and -0.5mm±0.7 [range, -2.2 to 0.5] (p=0.21). There was likewise no significant difference in varus tilt. The number of ectopic ossifications did not differ, despite the absence of shoulder: 7 with SL-PLUS™ (23%), and 10 with SL-PLUS MIA™ (32%), without clinical impact. Oxford score improved from 43±6.8 to 19±7 at 5 years' follow-up with SL-PLUS ™ and from 44±8.8 to 20±7.4 with SL-PLUS MIA™: i.e., no significant inter-group difference. Likewise, Harris score at 2 years' follow-up did not differ: 91.6±8.7 and 89.7±10.2, respectively. Implant survival did not differ: SL-PLUS MIA™, 41/41 (100%); SL-PLUS™, 36/38 (94.7%) (p=0.13). CONCLUSION: There was no significant difference in fixation quality between the SL-PLUS™ and SL-PLUS MIA™ implants. Elimination of the shoulder did not jeopardize primary or secondary fixation, but neither did it reduce the rate of ossification. The modified Zweymüller implant appeared risk-free at 6 years' follow-up. LEVEL OF EVIDENCE: II, low-power prospective randomized study.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Seguimentos , Humanos , Estudos Prospectivos , Desenho de Prótese , Falha de Prótese , Estudos Retrospectivos
18.
Mol Cell Proteomics ; 19(1): 31-49, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744855

RESUMO

The science that investigates the ensembles of all peptides associated to human leukocyte antigen (HLA) molecules is termed "immunopeptidomics" and is typically driven by mass spectrometry (MS) technologies. Recent advances in MS technologies, neoantigen discovery and cancer immunotherapy have catalyzed the launch of the Human Immunopeptidome Project (HIPP) with the goal of providing a complete map of the human immunopeptidome and making the technology so robust that it will be available in every clinic. Here, we provide a long-term perspective of the field and we use this framework to explore how we think the completion of the HIPP will truly impact the society in the future. In this context, we introduce the concept of immunopeptidome-wide association studies (IWAS). We highlight the importance of large cohort studies for the future and how applying quantitative immunopeptidomics at population scale may provide a new look at individual predisposition to common immune diseases as well as responsiveness to vaccines and immunotherapies. Through this vision, we aim to provide a fresh view of the field to stimulate new discussions within the community, and present what we see as the key challenges for the future for unlocking the full potential of immunopeptidomics in this era of precision medicine.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Peptídeos/química , Peptídeos/imunologia , Alelos , Estudos de Coortes , Humanos , Imunoterapia , Infecções/diagnóstico , Infecções/terapia , Espectrometria de Massas , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina de Precisão , Prognóstico
19.
Sci Data ; 5: 180157, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30084848

RESUMO

The large array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC class I immunopeptidome. Although the MHC class I immunopeptidome is ubiquitous in mammals and represents a critical component of the immune system, very little is known, in any species, about its composition across most tissues and organs in vivo. We applied mass spectrometry (MS) technologies to draft the first tissue-based atlas of the murine MHC class I immunopeptidome in health. Peptides were extracted from 19 normal tissues from C57BL/6 mice and prepared for MS injections, resulting in a total number of 28,448 high-confidence H2Db/Kb-associated peptides identified and annotated in the atlas. This atlas provides initial qualitative data to explore the tissue-specificity of the immunopeptidome and serves as a guide to identify potential tumor-associated antigens from various cancer models. Our data were shared via PRIDE (PXD008733), SysteMHC Atlas (SYSMHC00018) and SWATH Atlas. We anticipate that this unique dataset will be expanded in the future and will find wide applications in basic and translational immunology.


Assuntos
Antígenos de Histocompatibilidade Classe I , Especificidade de Órgãos , Animais , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos
20.
Proteomics ; 18(12): e1800110, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29791771

RESUMO

Minimal information about an immuno-peptidomics experiment (MIAIPE) is an initiative of the members of the Human Immuno-Peptidome Project (HIPP), an international program organized by the Human Proteome Organization (HUPO). The aim of the MIAIPE guidelines is to deliver technical guidelines representing the minimal information required to sufficiently support the evaluation and interpretation of immunopeptidomics experiments. The MIAIPE document has been designed to report essential information about sample preparation, mass spectrometric measurement, and associated mass spectrometry (MS)-related bioinformatics aspects that are unique to immunopeptidomics and may not be covered by the general proteomics MIAPE (minimal information about a proteomics experiment) guidelines.


Assuntos
Biologia Computacional/normas , Antígenos de Histocompatibilidade Classe II/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteômica/normas , Software , Manejo de Espécimes/normas , Bases de Dados de Proteínas , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia
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