Improving access to kidney transplantation for highly sensitized patients: What is the role of IL-6 pathway blockade in desensitization protocols? (notice n° 192092)
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| fixed length control field | 02882cam a2200205 4500500 |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20250112044755.0 |
| 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 | Improving access to kidney transplantation for highly sensitized patients: What is the role of IL-6 pathway blockade in desensitization protocols? |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
| Date of publication, distribution, etc. | 2022.<br/> |
| 500 ## - GENERAL NOTE | |
| General note | 75 |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | BackgroundDesensitization allows kidney transplantation for highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (a monoclonal antibody directed against the IL-6 receptor) could potentially improve the efficacy of desensitization.MethodsWe conducted a systematic review using the following MeSH terms in PubMed: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft, and desensitization.StudiesIL-6 plays a role in humoral response (plasma cell differentiation induced by T cells, IL-21 secretion) as well as in cellular response (differentiation of T cells to Th17 rather than Treg). In desensitization, tocilizumab was first studied as a second-line treatment after failure of standard-of-care (apheresis and rituximab ± IgIV). A recent study showed that tocilizumab monotherapy attenuated anti-HLA antibody levels, but not enough to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cell maturation. Tocilizumab could potentially therefore improve the long-term efficacy of desensitization, by limiting anti-HLA rebound and thus preventing antibody-mediated rejection. This hypothesis is supported by a recent study that used clazakizumab (a monoclonal antibody directed against IL-6) in combination with standard-of-care. In this study, clazakizumab was continued after kidney transplantation. The results were encouraging: 9/10 patients received a transplant, and 6 months post-transplant none of them had developed donor-specific antibodies.ConclusionIL-6 pathway blockade monotherapy fails to desensitize highly sensitized kidney transplant candidates. In combination with standard-of-care, it does not appear to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve the long-term prognosis of HLA-incompatible transplant by orienting the response toward a tolerogenic profile, by hindering B-cell maturation and thereby preventing DSA rebound after transplantation. This hypothesis requires confirmation in further studies. |
| 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/journal-nephrologie-therapeutique-2022-7-page-577?lang=en">https://shs.cairn.info/journal-nephrologie-therapeutique-2022-7-page-577?lang=en</a> |
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