Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: We have recently reported successful use of Tocilizumab (TCZ), an anti-IL-6 receptor (R) monoclonal antibody, for cABMR treatment in HLA-sensitized kidney transplant (KTx) Pts. Total IgG, anti-HLA IgG and IgG subclasses were significantly reduced post-TCZ. CLZ is 3-120 times more potent than TCZ in inhibiting IL-6/IL-6R signaling in vitro. A clinical trial aimed at improving cABMR using CLZ in sensitized KTx Pts is now underway. Here, we report on measurement of IgG, IgM, IgA, IgG subclasses, anti-HLA IgG and donor specific antibody (DSA) levels pre- and post-CLZ treatment of Pts with cABMR.
*Methods: Plasma samples obtained pre- & at 6 months post-CLZ (25mg SQ, monthly) from 7 Pts with cABMR were tested for total IgG, IgM, IgA and IgG1-4 subclasses by ELISA. Anti-HLA IgG and DSAs were measured by single bead Luminex assay. The anti-HLA IgG and DSA (class I & class II) levels were expressed as a relative intensity score; Score 10, 5, 2 and 0 for MFI >10K, 5K-10K, <5K and no HLA antibody, respectively, are given to each detected antibody, and the sum of these are the final score for plasma with multiple HLA antibodies.
*Results: Total IgG, IgG1 and IgG2 significantly decreased post-CLZ, while no reduction was seen in total IgM, IgA, IgG3 and IgG4 (Table 1). Anti-HLA IgG was also significantly reduced post-CLZ; 4 of 7 Pts (57%) showed reduction post-CLZ and the remaining 3 pts with low scores (<6) no change. DSA was reduced post-CLZ in 2 Pts, and 3 with DSA and 2 without DSA showed no change.
*Conclusions: CLZ suppresses Ig production including total IgG, IgG1, IgG2, anti-HLA IgG and DSA likely due to non-specific B cell suppression by blocking the effect of IL-6. This may contribute to improvement of cABMR in this Pt population. A larger study with longer follow-up is required for confirming the findings.
To cite this abstract in AMA style:Shin B, Ammerman NF, Vo AA, Zhang X, Jordan SC, Toyoda M. Clazakizumab (CLZ, Anti-IL-6 Monoclonal Antibody) Treatment of Patients (Pts) with Chronic Antibody-Mediated Rejection (cABMR) Reduces Total Immunoglobulin (Ig) and Anti-HLA IgG Antibody Levels [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/clazakizumab-clz-anti-il-6-monoclonal-antibody-treatment-of-patients-pts-with-chronic-antibody-mediated-rejection-cabmr-reduces-total-immunoglobulin-ig-and-anti-hla-igg-antibody-levels/. Accessed October 26, 2020.
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