Améliorer l’accès à la transplantation rénale des sujets hyperimmunisés : quelle place pour un blocage de la voie de l’IL-6 dans les protocoles de désimmunisation ? (notice n° 760428)
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| fixed length control field | 05324cam a2200337 4500500 |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20250123102253.0 |
| 041 ## - LANGUAGE CODE | |
| Language code of text/sound track or separate title | fre |
| 042 ## - AUTHENTICATION CODE | |
| Authentication code | dc |
| 100 10 - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Weinhard, Jules |
| Relator term | author |
| 245 00 - TITLE STATEMENT | |
| Title | Améliorer l’accès à la transplantation rénale des sujets hyperimmunisés : quelle place pour un blocage de la voie de l’IL-6 dans les protocoles de désimmunisation ? |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
| Date of publication, distribution, etc. | 2022.<br/> |
| 500 ## - GENERAL NOTE | |
| General note | 70 |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | ContexteLa désimmunisation améliore l’accès à la greffe rénale des sujets hyperimmunisés. La place centrale de l’IL-6 dans la réponse immunitaire fait du tocilizumab (anticorps monoclonal anti-IL-6R) une molécule d’intérêt pour optimiser l’efficacité de la désimmunisation. MéthodeIl s’agit d’une revue systématique ayant utilisé sur Pubmed les MeSH terms : tocilizumab, clazakizumab, Interleukin-6 blockade, kidney transplantation, kidney graft, desensitization. Études récentesL’IL-6 est impliquée dans la réponse humorale (sécrétion d’IL-21 permettant la différenciation des plasmocytes) et cellulaire (différenciation du lymphocyte T vers un profil Th17 plutôt que T régulateur). En matière de désimmunisation, une première étude a suggéré l’intérêt du tocilizumab après l’échec du protocole standard (aphérèse, rituximab, immunoglobulines polyvalentes par voie intraveineuse). Une étude récente a montré qu’en monothérapie, le tocilizumab diminuait le taux d’anticorps anti-HLA mais insuffisamment pour autoriser une greffe rénale. L’immunophénotypage lymphocytaire a toutefois montré un blocage de la maturation des cellules B sous tocilizumab, suggérant l’intérêt potentiel (à plus long terme) du tocilizumab pour prévenir le rebond des anticorps anti-HLA. Cette hypothèse est étayée par une récente étude où le clazakizumab (anticorps monoclonal anti-IL-6), associé au protocole standard et poursuivi après la greffe, permettait à 9 patients sur 10 d’être greffés. Ceux-ci n’avaient développé aucun donor specific antibody à 6 mois post-greffe. ConclusionLe blocage de l’IL-6 en monothérapie est insuffisant. En association à un protocole standard, il ne semble pas améliorer l’accès à la greffe par rapport au protocole standard seul. Il pourrait cependant en améliorer les résultats à long terme (moindre risque de rejet humoral) en bloquant la maturation des cellules B et orientant la réponse vers un profil tolérogène. Ceci reste à démontrer par de futures études. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | BackgroundDesensitization allows kidney transplantation for HLA highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (monoclonal antibody directed against IL-6 receptor) could probably improve desensitization efficacy. MethodsPubmed systematic review by using MeSH terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization. StudiesIL-6 plays a role in humoral response (plasmocyte differentiation induced by lymphocyte T, IL-21 secretion) as well as in cellular response (differentiation of LT Th17 rather than T reg). In desensitization field, tocilizumab was first studied as second-line treatment after failing of standard-of-care (apheresis, rituximab ± IgIV). Recent study showed that tocilizumab as a monotherapy attenuated anti-HLA antibodies rates but was not sufficient to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cells maturation. Thereby, tocilizumab could improve long-term efficacy of desensitization, by limiting the anti-HLA rebound and so avoiding antibody-mediated rejection. This hypothesis is supported by a recent study which used clazakizumab (monoclonal antibody directed against IL-6) in association with standard-of-care. In that study, clazakizumab was continued after kidney transplantation. Results were encouraging because 9/10 patients were transplanted and there was no donor-specific antibody at 6 months post-transplantation. ConclusionIL-6 pathway blockade as a monotherapy fails to desensitize HLA highly sensitized kidney transplant candidates. In association with standard-of-care, it does not seem to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve long-term prognosis of HLA incompatible transplantation by orienting the response towards a tolerogenic profile, by hindering B-cell maturation and, thereby, avoiding DSA rebounds after transplantation. This hypothesis needs to be proven by further studies. |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Tocilizumab |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Clazakizumab |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Greffe rénale |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Désimmunisation |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Anticorps anti-HLA |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Kidney transplantation |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Anti-HLA alloantibody |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Tocilizumab |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Desensitization |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | Clazakizumab |
| 700 10 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Noble, Johan |
| Relator term | author |
| 700 10 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Jouve, Thomas |
| Relator term | author |
| 700 10 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Malvezzi, Paolo |
| Relator term | author |
| 700 10 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Rostaing, Lionel |
| Relator term | author |
| 786 0# - DATA SOURCE ENTRY | |
| Note | Néphrologie & Thérapeutique | Volume 18 | 7 | 2022-07-26 | p. 577-583 | 1769-7255 |
| 856 41 - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | <a href="https://shs.cairn.info/revue-nephrologie-et-therapeutique-2022-7-page-577?lang=fr&redirect-ssocas=7080">https://shs.cairn.info/revue-nephrologie-et-therapeutique-2022-7-page-577?lang=fr&redirect-ssocas=7080</a> |
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