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Grant support

This study was funded by the following grants: Fondecyt 1181853, Fondef-IDeA ID15I10080; Fondef-IDeA ID15I20080, Fondef-IDeA ID18I10243, and REDES 180028, from ANID, Chile; and by Project RTI2018-097414-B-I00 from the Spanish Ministry of Science. Doctoral training of JM was supported by ANID-PFCHA/National Doctoral Scholarship 2018/No 21181538.

Analysis of institutional authors

Maggi JAuthorCarrascal MAuthorAbian JAuthor
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Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis

Publicated to:Annals Of The Rheumatic Diseases. 81 (8): 1096-1105 - 2022-08-01 81(8), DOI: 10.1136/annrheumdis-2021-220371

Authors: Maggi, J; Soto, L; Aravena, O; Catalan, D; Aguillón, JC; Carrascal, M; Abian, J; Neira, O; Cuéllar, MC; James, EA; Jaraquemada, D

Affiliations

Benaroya Res Inst, Translat Res Program, Seattle, WA USA - Author
Biological and Environmental Proteomics Group, IIBB-CSIC, IDIBAPS, Barcelona, Spain. - Author
Departamento de Medicina, Unidad del Dolor, Hospital Clinico de la Universidad de Chile Jose Joaquin Aguirre, Santiago, Chile. - Author
IIBB CSIC, IDIBAPS, Biol & Environm Prote Grp, Barcelona, Spain - Author
Immune Regulation and Tolerance Research Group, Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile Facultad de Medicina, Santiago, Chile jaguillo@med.uchile.cl dfcatalan@med.uchile.cl. - Author
Immune Regulation and Tolerance Research Group, Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile Facultad de Medicina, Santiago, Chile. - Author
Immunology Unit, Cell Biology, Physiology and Immunology Department, Institut de Biotecnologia i Biomedicina, Universitat de Barcelona, Barcelona, Spain. - Author
Servicio de Reumatología, Hospital del Salvador, Universidad de Chile, Santiago, Chile. - Author
Translational Research Program, Benaroya Research Institute, Seattle, Washington, USA. - Author
Univ Barcelona, Inst Biotecnol & Biomed, Physiol & Immunol Dept, Immunol Unit, Barcelona, Spain - Author
Univ Chile Jose Joaquin Aguirre, Dept Med, Unidad Dolor, Hosp Clin, Santiago, Chile - Author
Univ Chile, Hosp Salvador, Serv Reumatol, Santiago, Chile - Author
Univ Chile, Inst Ciencias Biomed ICBM, Programa Disciplinario Inmunol, Immune Regulat & Tolerance Res Grp,Fac Med, Santiago, Chile - Author
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Abstract

Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA.HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry.We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity.We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords
antibodiesassociationautoantibodiesautoimmunityb-cellcomplement componentscomplexesexpressionimmune-responseproteinrheumatoidsynovial fluidt-lymphocyte subsetsArthritisArthritis, rheumatoidAutoimmunityDendritic cellsEpitopeEpitopes, t-lymphocyteHla dr antigenHla-dr antigensHumanHumansLeukocytes, mononuclearMononuclear cellPeptidePeptidesRheumatoid arthritisSynovial fluidT-lymphocyte subsets

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Annals Of The Rheumatic Diseases due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 2/34, thus managing to position itself as a Q1 (Primer Cuartil), in the category Rheumatology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.25, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-17, the following number of citations:

  • WoS: 8
  • Scopus: 12
  • Europe PMC: 3
  • OpenCitations: 9
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-17:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 24.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 24 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Chile; El Salvador; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Maggi Orellana, Jaxaira) .