A5020557161- Renal Transplantation Outcomes and Treatments
- Renal Diseases and Glomerulopathies
- SARS-CoV-2 and COVID-19 Research
- Complement system in diseases
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Blood groups and transfusion
- Viral Infections and Immunology Research
- Mycobacterium research and diagnosis
- Xenotransplantation and immune response
- Drug-Induced Adverse Reactions
- Pregnancy and Medication Impact
- Systemic Lupus Erythematosus Research
- Cytokine Signaling Pathways and Interactions
- Respiratory Support and Mechanisms
- Hematopoietic Stem Cell Transplantation
- Peripheral Neuropathies and Disorders
- Pharmacological Effects and Toxicity Studies
- Adenosine and Purinergic Signaling
- Intensive Care Unit Cognitive Disorders
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Electrolyte and hormonal disorders
Cedars-Sinai Medical Center
2018-2024
Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food Drug Administration for treatment of associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use tocilizumab in SARS-CoV-2 pneumonia.
Delayed graft function (DGF) is defined as need for dialysis early posttransplant. DGF related to ischemia-reperfusion injury (IRI) that diminishes allograft and may be complement dependent. Here, we investigate the ability of C1 esterase inhibitor (C1INH) prevent IRI/DGF in kidney transplant recipients. Seventy patients receiving deceased donor transplants at risk were randomized receive C1INH 50 U/kg (#35) or placebo intraoperatively 24 hours. The primary end point was hemodialysis during...
Interleukin-6 (IL-6) is an important mediator of inflammation and activation T cells, B plasma cells. Excessive IL-6 production linked to human diseases characterized by unregulated antibody production, including alloimmunity, where persistence donor-specific antibodies (DSAs), chronic active antibody-mediated rejection (cAMR), graft loss are noted. Here, we report our experience investigating clazakizumab, a novel inhibitor, in treating leukocyte antigen (HLA)-sensitized patients with...
Visual Abstract Export Background and objectives Delayed graft function is related to ischemia-reperfusion injury may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated shorter duration of delayed higher eGFR at 1 year. Here, we report longer-term outcomes this trial. Design, setting, participants, & measurements This post hoc analysis phase 1/2, controlled enrolling 70 recipients deceased donor...
Modification of pathogenic antibodies and their effector functions in autoimmune diseases or use B cell/plasma cell-directed anticancer therapies have illuminated the biologic relevance cells, plasma cells (PCs), complement alloimmunity. They also rejuvenated interest how mediate multiple that include antibody production, antigen presentation to T costimulation, production immune stimulating modulatory cytokines drive dysfunctional responses. Current methods reduce alloantibodies are only...
Alloantibodies are a significant barrier to successful transplantation. While desensitization has emerged, efficacy is limited. Interleukin-6 (IL-6) an important mediator of inflammation and immune cell activation. Persistent IL-6 production increases the risk for alloantibody production. Here we report our experience with clazakizumab (anti-IL-6) highly HLA-sensitized patients (HS). From March 2018 September 2020, 20 HS were enrolled in open label pilot study assess safety limited...
Assessing the composition of immune responses to SARS-CoV-2 vaccines is critical for our understanding protective immunity, especially compromised patients. The Pfizer (BNT162b2) vaccination showed >90% efficacy in protecting individuals from infection. However, these studies did not examine immunocompromised kidney transplant patients (KT). Subsequent reports KT have shown severe deficiencies Spike-specific immunoglobin G (IgG) prompting booster vaccinations, but a broader T-cell immunity...
Interleukin-6 (IL-6) is a cytokine critical for innate and adaptive immune responses. However, persistent expression of high levels IL-6 are associated with number pathologic conditions including autoimmune diseases capillary leak syndrome. Importantly, in kidney transplant patients, may play role mediation cell-mediated rejection (CMR) antibody-mediated (AMR). This likely due to the importance stimulating B cell responses pathogenic donor-specific antibody (DSA) generation stimulation T...
Awareness of drug-drug interactions is critical in organ transplant recipient management. However, biologic agents interfering with monoclonal antibodies not widely considered. We report the effect high-dose intravenous immunoglobulin (IVIg) on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) human anti-C5 antibody tesidolumab (LFG316) end-stage renal disease patients awaiting kidney transplant. In this single-center, phase 1, open-label, parallel-group study, 8 were...
Higher Banff inflammation and chronicity scores on kidney transplant biopsies are associated with poorer graft survival, although histology alone has limitations in predicting outcomes. We investigated if integrating donor-derived cell-free DNA (dd-cfDNA, Allosure; CareDx, Inc.) biopsy into a predictive model for estimated glomerular filtration rate over time can improve prognostic assessment versus alone.We identified 180 patients dd-cfDNA assessed within 1 mo of biopsy. Using linear...
Although the incidence of acute antibody mediated rejection in liver transplantation is low, consequences can be devastating, often leading to severe fibrotic changes and early graft loss. Conventional treatment modalities for management moderate-to-severe transplant continue rely on corticosteroids, plasmapheresis, intravenous immunoglobulin. However, refractory, remains without a clear gold-standard approach. This case report describes successful first use Imlifidase, an Ig-G degrading...
Purpose of review Human leukocyte antigen (HLA) sensitization is a major barrier to kidney transplantation induced by exposure alloantigens through pregnancy, blood product and previous transplantations. Desensitization strategies are undertaken improve the chances finding compatible organ offers. Standard approaches desensitization include use plasmapheresis/low dose intravenous immunoglobulin (IVIG) or high IVIG plus anti-CD20. However, current methods reduce HLA antibodies not always...
Purpose: IL-6 mediates inflammation and activation of T-cells, B-cells & plasma cells. Thus, may represent an important target for desensitization (DES). Here we report a 12M follow-up this single center Phase I/II study to assess safety efficacy Clazakizumab (anti-IL-6, Vitaeris) DES in highly-HLA sensitized (HS) patients. Methods: Ten HS patients (cPRA >50%) received PLEX x5 followed by IVIg 2gm/kg X1. Post-IVIg, anti-IL-6 25mg SC Q4W X6 with monitoring HLA antibody other immune...
To The Editor: Understanding the composition and duration of immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is critical for prevention infection. most elements immunity SARS-CoV-2 are neutralizing antibody T-cell immunity. Current assessments risk infections largely depended on detection antibodies SARS-CoV-2. However, taken alone, this represents an often-unreliable tool due evanescent nature spike immunoglobulin G (IgG) responses.1-3 Here,...
Introduction: Highly sensitized (HS) patients are at an increased risk for chronic antibody mediated rejection (cABMR) and graft loss due to persistent, deleterious DSA production. Therapeutic options currently available prevent treat cABMR limited. Here, we report our updated, 18 month experience using clazakizumab, a novel anti-IL-6 monoclonal, in HS with + transplant glomerulopathy (TG). Patients & Methods: Since February 2018, 10 adult biopsy proven +TG DSA+ were enrolled phase I/II,...