Immune Cell Subset Profiles in HLA-Sensitized Kidney Transplant Patients (HS KTx Pts) Desensitized with Clazakizumab (CLZ, Humanized Anti-IL-6 Monoclonal Antibody) Followed by Transplantation (Tx)
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-092
Keywords: B cells, Leukocytes, Natural killer cells, 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, B cell growth factor, increases follicular T helper cell (Tfh) activity, promoting plasmablast (PB) and plasma cell (PC) differentiation, and antibody production. A clinical trial to use CLZ as a desensitization (DES) agent in HS KTx Pts is underway. Here, we monitor immune cell subsets pre- & post-DES and post-Tx in these Pts.
*Methods: DES consisted of plasma-exchange (×5) + IVIG (2 mg/kg, x1) + monthly CLZ (25 mg, SQ, ×7) w/ additional CLZ (×7) post-Tx w/ alemtuzumab induction (ALZ). Whole 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), CD8+ (T8), CD19+ (B), CD56+ (NK), CD38hiCD24hi (Breg), CD38hiCD27hiCD138- (PB), CD38hiCD27hiCD138+ (PC) & CXCR5+ICOS+PD-1+ (Tfh) 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 & post-Tx. Pre-DES total L% in WBC (21±10%, 5 Pts w/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. A similar trend was observed in T3, T4, T8, B and NK cell% in WBC although some Pts already showed pre-DES B and NK cell% post-Tx. Breg% in WBC also increased post-DES and the increased Breg% remained post-Tx in 70% of the Pts. Breg% in B did not change post-DES, and it increased post-Tx (Table). In contrast, PB% and PC% in WBC and B also did not change post-DES, but nearly significant decreased post-Tx. Tfh cell% in WBC also increased post-DES and then became extremely low post-Tx, and Tfh% in T4 did not significant change at all time points.
*Conclusions: DES w/ CLZ followed by Tx w/ ALZ and additional post-Tx CLZ maintained Breg activity, reduced PB and PC number, and minimized Tfh activity, likely via IL-6 signaling blockade. These may contribute to the low ABMR rate observed in this Pt population.
| Cell Subsets (reference, %) | Parent Cells | Pre-Tx | 6M post-Tx | |
| pre-DES | post-DES | |||
| Breg (1.9-14.7) | B | 25±31 | 26±30 | 48±26* |
| PB (0.10-4.95) | B | 0.8±0.9 | 1.7±2.7 | 0.1±0.1* |
| PC (0.0-0.22) | B | 0.6±0.7 | 0.6±1.1 | 0.2±0.4# |
| Tfh (0.14-0.61) | T4 | 0.2±0.1 | 0.3±0.3 | 0.6±1.1 |
| *p=0.05-0.1, # PC% reduction in 7/8 Pts | ||||
To cite this abstract in AMA style:
Ge S, Chu M, Guzman AD, Ortiz ED, Vo A, Ammerman N, Jordan SC, Toyoda M. Immune Cell Subset Profiles in HLA-Sensitized Kidney Transplant Patients (HS KTx Pts) Desensitized with Clazakizumab (CLZ, Humanized Anti-IL-6 Monoclonal Antibody) Followed by Transplantation (Tx) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/immune-cell-subset-profiles-in-hla-sensitized-kidney-transplant-patients-hs-ktx-pts-desensitized-with-clazakizumab-clz-humanized-anti-il-6-monoclonal-antibody-followed-by-transplantation-tx/. Accessed November 24, 2024.« Back to 2020 American Transplant Congress