April 9, 2018
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Tofacitinib halts progression of graft dysfunction in a rat model of mixed cellular and humoral rejection.

Publicated to: Transplantation. 102 (7): 1075-1084 - 2018-07-01 102(7), DOI: 10.1097/TP.0000000000002204

Authors:

Rovira, Jordi; Ramirez-Bajo, Maria Jose; Banon-Maneus, Elisenda; Lazo-Rodriguez, Marta; Moya-Rull, Daniel; Hierro-Garcia, Natalia; Tubita, Valeria; Pineiro, Gaston J; Revuelta, Ignacio; Ventura-Aguiar, Pedro; Cucchiari, David; Oppenheimer, Federico; Brunet, Merce; Campistol, Josep M; Diekmann, Fritz
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Affiliations

FCRB, LENIT, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Villarroel 170 Escala 12 Planta 5, E-08036 Barcelona, Spain.      University of Barcelona    Hospital Clinic de Barcelona - Author
Hosp Clin Barcelona, ICNU, Dept Nefrol & Trasplantament Renal, Barcelona, Spain      University of Barcelona    Hospital Clinic de Barcelona - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, LENIT, Barcelona, Spain      IDIBAPS    Hospital Clinic de Barcelona    University of Barcelona       - Author
Red Invest Renal REDINREN, Madrid, Spain       - Author
Univ Barcelona, Hosp Clin Barcelona, Ctr Diagnost Biomed, Lab Farmacol & Toxicol,Serv Bioquim & Genet Mol, Barcelona, Spain      Hospital Clinic de Barcelona    University of Barcelona - Author
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Abstract

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Background The progression from acute to chronic antibody-mediated rejection in kidney transplant recipients is usually not prevented by current therapeutic options. Here, we investigated whether the use of tofacitinib (TOFA), a Janus kinase 3 inhibitor, was capable of preventing the progression of allograft dysfunction in a Fisher-to-Lewis rat model of kidney transplantation. Methods Rats were treated from the third week after transplantation to allow the development of rejection. Treatment was based on cyclosporin A, rapamycin or TOFA. Renal function was assessed at 1, 4, 8, and 12 weeks after transplantation, whereas rat survival, histological lesions, and infiltrating lymphocytes were analyzed at 12 weeks. Results Tofacitinib prolonged graft survival, preserved tubular and glomerular structures and reduced humoral damage characterized by C4d deposition. Tofacitinib was able to reduce donor-specific antibodies. In addition, T and natural killer cell graft infiltration was reduced in TOFA-treated rats. Although rapamycin-treated rats also showed prolonged graft survival, glomerular structures were more affected. Moreover, only TOFA treatment reduced the presence of T, B and natural killer cells in splenic parenchyma. Conclusions Tofacitinib is able to reduce the immune response generated in a rat model of kidney graft rejection, providing prolonged graft and recipient survival, better graft function, and less histological lesions.
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Keywords

antibodiescellscp-690550immunosuppressive drugsjak3 inhibitor cp-690,550nonhuman-primatesorgan-transplantationpreventionrenal-allograft recipientsAnimalsChronic diseaseComplement c4bComplement c4dDisease models, animalDisease progressionGraft rejectionGraft survivalHumansImmunity, cellularImmunity, humoralImmunosuppressive agentsJak3 protein, ratJanus kinase 3KidneyKidney transplantationKidney-transplant patientsMalePeptide fragmentsPiperidinesProtein kinase inhibitorsPyrimidinesPyrrolesRatsRats, inbred f344Rats, inbred lewSignal transductionTofacitinibTreatment outcome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Transplantation 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, 2018, it was in position 10/203, thus managing to position itself as a Q1 (Primer Cuartil), in the category Surgery. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-28:

  • Google Scholar: 19
  • WoS: 15
  • Scopus: 7
  • Europe PMC: 7
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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 2025-12-28:

  • 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: 16.
  • 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: 16 (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: 1.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).
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Leadership analysis of institutional authors

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 (Rovira Juarez, Jordi) and Last Author (Diekmann, Fritz).

the author responsible for correspondence tasks has been Diekmann, Fritz.

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Awards linked to the item

This study has been funded by the project PI11/01112 and Redes Tematicas De Investigacion Cooperativa En Salud, REDINREN (RD12/0021/0028 and RD16/0009/0023) both co-funded by ISCIII-Subdireccion General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa. CERCA Programme/Generalitat de Catalunya. This work was developed at the Centre de Recerca Biomedica Cellex, Barcelona, Spain.
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