[Improving access to kidney transplantation for highly sensitized patients: What place for IL-6 pathway blockade in desensitization protocols?] / 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 ?
Nephrol Ther
; 18(7): 577-583, 2022 Dec.
Article
in Fr
| MEDLINE
| ID: mdl-36328901
ABSTRACT
BACKGROUND:
Desensitization 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.METHODS:
Pubmed systematic review by using MeSH terms tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization. STUDIES IL-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.CONCLUSION:
IL-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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kidney Transplantation
Limits:
Humans
Language:
Fr
Journal:
Nephrol Ther
Journal subject:
NEFROLOGIA
/
TERAPEUTICA
Year:
2022
Document type:
Article
Affiliation country: