Imlifidase-generated Single-cleaved IgG: Implications for Transplantation

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Bockermann, RobertHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)

Imlifidase-generated Single-cleaved IgG : Implications for Transplantation

Artikel/kapitelEngelska2022

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Ovid Technologies (Wolters Kluwer Health),2022
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LIBRIS-ID:oai:DiVA.org:uu-479904
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-479904URI
https://doi.org/10.1097/TP.0000000000004031DOI

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Språk:engelska
Sammanfattning på:engelska

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Background. Imlifidase is an immunoglobulin G (IgG)-specific protease conditionally approved in the EU for desensitization in highly sensitized crossmatch positive kidney transplant patients. Imlifidase efficiently cleaves both heavy chains of IgG in a 2-step process. However, low levels of the intermediate cleavage product, single-cleaved IgG (scIgG), may persist in the circulation. The study objective was to investigate Fc-mediated effector functions of scIgG and its potential impact on common clinical immunologic assays used to assess transplant eligibility.Methods. Imlifidase-generated scIgG, obtained by in vitro cleavage of HLA-sensitized patient serum or selected antibodies, was investigated in different complement- and Fc gamma R-dependent assays and models, including clinical tests used to evaluate HLA-specific antibodies.Results. ScIgG had significantly reduced Fc-mediated effector function compared with intact IgG, although some degree of activity in complement- and Fc gamma R-dependent models was still detectable. A preparation of concentrated scIgG generated from a highly HLA-sensitized individual gave rise to a positive signal in the anti-HLA IgG LABScreen, which uses anti-Fc detection, but was entirely negative in the C1qScreen. The same high-concentration HLA-binding scIgG preparation also generated positive complement-dependent cytotoxicity responses against 80%-100% of donor T and B cells, although follow-up titrations demonstrated a much lower intrinsic activity than for intact anti-HLA IgG.Conclusions. ScIgG has a significantly reduced capacity to mediate Fc-dependent effector functions. However, remaining HLA-reactive scIgG in plasma after imlifidase treatment can cause positive assay results equivalent to intact IgG in clinical assays. Therefore, complete IgG cleavage after imlifidase treatment is essential to allow correct decision-making in relation to transplant eligibility.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

Jarnum, SofiaHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)
Runstrom, AnnaHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)
Lorant, Tomas,1975-Uppsala universitet,Transplantationskirurgi(Swepub:uu)tomalora (författare)
Winstedt, LenaHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)
Palmqvist, NiklasHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)
Kjellman, ChristianHansa Biopharma AB, Box 785, S-22007 Lund, Sweden (författare)
Hansa Biopharma AB, Box 785, S-22007 Lund, SwedenTransplantationskirurgi (creator_code:org_t)

Sammanhörande titlar

Ingår i:Transplantation: Ovid Technologies (Wolters Kluwer Health)106:7, s. 1485-14960041-13371534-6080

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Av författaren/redakt...: Bockermann, Robe ...; Jarnum, Sofia; Runstrom, Anna; Lorant, Tomas, 1 ...; Winstedt, Lena; Palmqvist, Nikla ...; visa fler...; Kjellman, Christ ...; visa färre...

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Artiklar i publikationen: Transplantation

Av lärosätet: Uppsala universitet

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