Pre- And Post-Transplant (Tx) Clazakizumab (CLZ, Humanized Anti-IL-6 Monoclonal Antibody) Treatment Increased Regulatory T Cell (Treg) Percentage in CD4+ T Cells in HLA-Sensitized Kidney Transplant Patients (HS KTx Pts)
1Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, 2Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
Meeting: 2020 American Transplant Congress
Abstract number: D-097
Keywords: Kidney transplantation, Leukocytes, Rejection, T cells
Session Information
Session Name: Poster Session D: Kidney Immunosuppression: Desensitization
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: IL-6 is a B cell growth factor and pro-inflammatory cytokine. Inhibition of IL-6 signaling modulates B cell activation and inflammatory process possibly through Treg induction. A clinical trial using CLZ as a desensitization (DES) agent in HS KTx Pts is underway. Here, we monitor Treg number pre- and post-DES and post-Tx in these Pts.
*Methods: DES consisted of plasma-exchange (×5) + IVIG (2 mg/kg, ×1) followed by monthly CLZ (25 mg, SQ, ×7) with additional CLZ (×7) post-Tx with alemtuzumab induction (ALZ). Heparinized blood collected from 10 Pts pre- & post-DES (pre-Tx) and at 6M post-Tx were submitted for flow cytometry analysis to monitor total lymphocytes (L), CD3+ (T3), CD4+ (T4) and CD25+CD127loFoxP3+ (Treg) cells. Cell% in WBC or parent cells were calculated.
*Results: WBC count was normal pre-DES (6.2±1.0 ×1000/μl) in all Pts and didn’t change post-DES and post-Tx. Pre-DES total L% in WBC (21±10%, 5 Pts with L% < normal) significantly increased post-DES (29±12%, p=0.01) followed by significant reduction at 6M post-Tx (7±4%. P=0.002) due to ALZ. Similarly, T3, T4 and Treg cell% in WBC increased post-DES followed by significant reduction post-Tx. T3 (pre-/post-DES/post-Tx: 81±6%/80±5%/40±25%**) and T4 (51±9%/48±6%/16±7%**) cell% in L did not change post-DES, and then significantly decreased post-Tx (**p<0.05), suggesting that T3 and T4 proportionally increased in L post-DES, but preferentially decreased in L post-Tx. In contrast, Treg cell% in T4 increased post-DES and then showed marked increases post-Tx (Table 1.), suggesting that Treg preferentially increased in T4 post-DES and post-Tx after T cell depletion likely due to CLZ inhibiting development of T-effector cells with deviation to Treg profile.
*Conclusions: Conclusions: DES with CLZ followed by Tx with ALZ and additional post-Tx CLZ increased Treg number, likely via IL-6 signaling blockade and possible resistance of Treg to ALZ cell depletion. These may contribute to the low ABMR rate observed in this Pt population.
| Cell Subsets (reference, %) | Pre-Tx | 6M post-Tx | |
| pre-DES | post-DES | ||
| Treg cell% in WBC (0.27-1.54) | 0.2±0.1 | 0.4±0.2** | 0.05±0.05** |
| Treg cell% in T4 (3.0-6.3) | 2.7±0.8 | 3.7±1.6* | 12.3±9.5** |
| **p<0.05, *p=0.05-0.1 | |||
To cite this abstract in AMA style:
Ge S, Chu M, Ortiz ED, Guzman AD, Vo A, Ammerman N, Jordan SC, Toyoda M. Pre- And Post-Transplant (Tx) Clazakizumab (CLZ, Humanized Anti-IL-6 Monoclonal Antibody) Treatment Increased Regulatory T Cell (Treg) Percentage in CD4+ T Cells in HLA-Sensitized Kidney Transplant Patients (HS KTx Pts) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/pre-and-post-transplant-tx-clazakizumab-clz-humanized-anti-il-6-monoclonal-antibody-treatment-increased-regulatory-t-cell-treg-percentage-in-cd4-t-cells-in-hla-sensitized-kidney-transplant-pa/. Accessed November 24, 2024.« Back to 2020 American Transplant Congress