Monitoring Inflammatory Cytokines in HLA-Sensitized Kidney Transplant Patients (HS KTx Pts) Desensitized with Clazakizumab (CLZ, Humanized Anti-IL-6 Monoclonal Antibody) Followed by Transplantation (Tx)

S. Ge¹, A. Petrosyan¹, M. Chu¹, N. Ammerman², A. Vo², X. Zhang³, S. C. Jordan², M. Toyoda¹

¹Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, ²Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, ³HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA

Meeting: 2020 American Transplant Congress

Abstract number: D-093

Keywords: Inflammation, Interferon (IFN), Rejection, Tumor necrosis factor (TNF)

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: Chronic inflammation and HLA sensitization are burdens for end stage renal disease Pts awaiting for a KTx. IL-6 is a pro-inflammatory cytokine responsible for activation of inate and adaptive immunity. Here, we report on inflammatory cytokine levels pre- and post-DES and post-Tx in patients treated with anti-IL-6 therapy for DES.

*Methods: DES consisted of plasma-exchange (×5) + IVIG (2 mg/kg, ×1) followed by monthly CLZ (25 mg, SQ, ×7) with additional CLZ (x7) post-Tx with alemtuzumab induction (ALZ). Archived serum samples obtained from 10 KTx Pts pre- & post-DES (pre-Tx) and at 6M post-Tx were submitted for IL-6, TNFα, IL-1β, IL-17A, IFNγ, IL-2, IL-10 (pg/ml) Luminex assay. Serum C-reactive protein (CRP) levels were recorded.

*Results: IL-6 levels significantly increased post-DES (1535±416, p=0.001) and at 6M post-Tx (1731±460, p=0.001). Pre-DES CRP levels in 5 of 10 Pts were elevated (13±17 mg/L), suggesting an ambient state of inflammation. Considering significant reduction of CRP post-DES (0.3±0.1 mg/L, p<0.05) and post-Tx (0.4±0.3 mg/L, p<0.05) in all pts, high levels of IL-6 detected were likely CLZ-bound IL-6, with no signaling capability via the IL-6R. IL-6 in 3/10 (30%), TNFα, IL-17A & IFNγ in 2 each/10 (20%) and IL-1β in 1/10 pts (10%) were elevated pre-DES compared to normal, and IL-2 & IL-10 were normal in all Pts. One of 10 Pts showed extremely high IL-6 (204), IL-1β (203), IL-17A (61), IFNγ (203) levels pre-DES, and those levels decreased post-Tx, but still remained high (IFNγ [51], IL-17a [24] and IL-1β [32]). Elevated pre-DES TNFα (37, 32) in 2 Pts became normal post-DES and post-Tx, while elevated IFNγ (37) and IL-17a (11) observed in another Pt remained high post-Tx. The remaining cytokines with normal levels remained normal post-DES and post-Tx.

*Conclusions: 1. CLZ efficiently blocks IL-6/IL-6R signaling, resulting in reduction of CRP levels, suggesting improvement of inflammation. 2. CLZ reduces elevated pre-DES inflammatory cytokine to normal levels and maintains the levels post-Tx in most patients. CLZ may create anti-inflammatory environment, reducing the risk for rejection in this Pt population.

To cite this abstract in AMA style:

Ge S, Petrosyan A, Chu M, Ammerman N, Vo A, Zhang X, Jordan SC, Toyoda M. Monitoring Inflammatory Cytokines 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/monitoring-inflammatory-cytokines-in-hla-sensitized-kidney-transplant-patients-hs-ktx-pts-desensitized-with-clazakizumab-clz-humanized-anti-il-6-monoclonal-antibody-followed-by-transplantation-t/. Accessed December 14, 2024.

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