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IgM single antigen ...
IgM single antigen bead HLA-assay is affected by imlifidase through the cleavage of IgG but not IgM
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- Runstrom, Anna (author)
- Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden.
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- Sjoholm, Kristoffer (author)
- Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden.
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- Roupe, Karl Markus (author)
- Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden.
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- Lorant, Tomas, 1975- (author)
- Uppsala universitet,Transplantationskirurgi
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- Kjellman, Christian (author)
- Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden.
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- Bockermann, Robert (author)
- Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden.
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Hansa Biopharma AB, Box 785, SE-22007 Lund, Sweden Transplantationskirurgi (creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: Transplant Immunology. - : Elsevier. - 0966-3274 .- 1878-5492. ; 68
- Related links:
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https://doi.org/10.1...
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Abstract
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- Aim: The aim of this study was to investigate if human IgM is a cleavable substrate for imlifidase and to explain an observed effect in anti-HLA IgM single antigen bead (SAB) assays in sensitized patients. Methods: Serum samples collected pre-and 24 h post-imlifidase administration from sensitized patients enrolled in a phase II trial were investigated for anti-HLA IgG and IgM using SAB assays, with and without in vitro IgG depletion using a CaptureSelectTM affinity matrix. In addition, pre-dose samples and purified human IgM samples were treated with imlifidase in vitro and evaluated by SDS-PAGE, Western blot (PE-conjugated anti-human IgM) and SAB (IgG, IgM) assays. Results: By comparing the mean fluorescence intensity (MFI) of HLA-beads, pre-and post-imlifidase administration, three IgM-related patterns were observed; IgM-specific HLA-SABs with an increased MFI post-imlifidase, IgM-specific HLA-SABs with a decreased MFI post-imlifidase, and IgM-specific HLA-SABs with a marginal MFI difference between the pre-and post-imlifidase administration. These IgM signal patterns were observed despite neither purified IgM nor serum IgM could be cleaved by imlifidase. After removing IgG, the effects observed on anti-HLA IgM was largely eliminated with the biggest differences seen in patients with very high anti-HLA IgG in pre-dose samples. Conclusion: We demonstrate that imlifidase does not cleave human IgM, including HLA-specific IgM antibodies from highly sensitized subjects. Observed decreases of SAB-HLA IgM signals after imlifidase treatment may result from the cleavage of IgG-IgM complexes which are bound to SAB-HLA. Serum analysis of patients with high levels of anti-HLA IgG will result in a more accurate SAB-HLA IgM reading after IgG depletion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Imlifidase
- IgG-IgM complexes
- SAB-HLA assay
- Donor-specific IgG
- Highly sensitized patients
Publication and Content Type
- ref (subject category)
- art (subject category)
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