Tocilizmab (Anti-IL-6R) Treatment (TCZ-Rx) Reduced Total IgG Levels Including Anti-HLA IgG: Analysis of IgG Subclasses (IgG1-IgG4) and Anti-HLA IgG Subclasses Show Similar Reductions in All Subclasses from Patients with DSA+ Chronic Antibody-Mediated Rejection (CABMR).
1Transplant Immunology Laboratory and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
2Terasaki Foundation Laboratory, Los Angeles
Meeting: 2017 American Transplant Congress
Abstract number: B75
Keywords: Antibodies, HLA antibodies, Immunoglobulins (Ig), Rejection
Session Information
Date: Sunday, April 30, 2017
Session Name: Poster Session B: Antibody Mediated Rejection in Kidney Transplant Recipients II
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: DSA+ CABMR constitutes the major cause for renal allograft loss in the U.S. Currently there are no approved therapies. We have reported TCZ use for pre-Tx desensitization (DES) and CABMR Rx. Complement- (CDC) and Ab-dependent cellular cytotoxicity (ADCC) are mechanisms for ABMR mediated primarily by IgG1&3 subclasses. We previously showed that TCZ-Rx reduced all 4 IgG subclasses, but reduction of IgG3 elevated pre-TCZ was most significant. Here we determined if TCZ-Rx reduced IgG1-4 subclasses and anti-HLA IgG subclasses. Methods: Archived plasma obtained pre- & post-TCZ-Rx (8mg/kg, 6x, monthly) from 15 Pts were tested for total IgG & IgG1-4 by ELISA, and anti-HLA total IgG, IgG3&4 by luminex. Anti-HLA total IgG (class I & II) levels were expressed as score (score 10, 5, 2 & 0 for SFI>200K, 100K-200K, <100K & 0, respectively, are given to each detected Ab), and IgG3&4 as MFI. The sum of the scores and MFIs were the final levels for serum w/ multiple Abs. Pre-TCZ IL-6 levels were also measured by luminex. Results: Total IgG, IgG1-4, and anti-HLA total IgG, DSA & IgG3 were significantly decreased post-TCZ (Table 1). No DSA was IgG3 subclass. Anti-HLA IgG4 also decreased, but not significantly. There was no correlation between pre-TCZ IL-6 and all types of IgGs tested. Conclusions: TCZ-Rx reduces total IgG, all 4 IgG subclass, anti-HLA total IgG, DSA, IgG3&4 subclass levels, indicating that IgG reduction by TCZ is non-specific via its anti-B cell property. This suggests that TCZ could reduce both CDC and ADCC-mediated ABMR.
| Pre-TCZ | post-TCZ | |
| Total IgG (mg/ml) | 13.0±2.5 | 10.8±3.0* |
| IgG1 ([mu]g/ml) | 9.5±5.2 | 6.9±4.6* |
| IgG2 ([mu]g/ml) | 4.0±2.4 | 2.4±1.0* |
| IgG3 ([mu]g/ml) | 1.3±1.4 | 0.7±0.5* |
| IgG4 ([mu]g/ml) | 0.3±0.2 | 0.2±0.2# |
| Anti-HLA-IgG (score) | 99±79 | 71±71* |
| DSA (score) | 10.0±8.7 | 4.8±6.8* |
| IgG3 (MFI, x1000) | 9.5±27.9 | 2.2±4.4* |
| IgG4 (MFI, x1000) | 2.4±7.2 | 0.5±1.3 |
*p<0.0.5 & 0.05<#P<0.1 vs. pre-TCZ.
CITATION INFORMATION: Shin B.-H, Everly M, Choi J, Ge S, Petrosyan A, Vo A, Jordan S, Toyoda M. Tocilizmab (Anti-IL-6R) Treatment (TCZ-Rx) Reduced Total IgG Levels Including Anti-HLA IgG: Analysis of IgG Subclasses (IgG1-IgG4) and Anti-HLA IgG Subclasses Show Similar Reductions in All Subclasses from Patients with DSA+ Chronic Antibody-Mediated Rejection (CABMR). Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Shin B-H, Everly M, Choi J, Ge S, Petrosyan A, Vo A, Jordan S, Toyoda M. Tocilizmab (Anti-IL-6R) Treatment (TCZ-Rx) Reduced Total IgG Levels Including Anti-HLA IgG: Analysis of IgG Subclasses (IgG1-IgG4) and Anti-HLA IgG Subclasses Show Similar Reductions in All Subclasses from Patients with DSA+ Chronic Antibody-Mediated Rejection (CABMR). [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/tocilizmab-anti-il-6r-treatment-tcz-rx-reduced-total-igg-levels-including-anti-hla-igg-analysis-of-igg-subclasses-igg1-igg4-and-anti-hla-igg-subclasses-show-similar-reductions-in-all-subclasses/. Accessed January 25, 2021.« Back to 2017 American Transplant Congress