Anti-Interleukin 6 Therapeutics for Chronic Antibody-Mediated Rejection In Kidney Transplant Recipients

Sharma, Rajeev

doi:10.6002/ect.2021.0254

Cited by 3 publications

(4 citation statements)

References 112 publications

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“…Consequently, understanding the natural history of de novo HLA-DSA is valuable for developing new strategies to prevent and treat both AMR and caAMR ( Fig. 1 ) [ 2 , 7 , 8 ].…”

Section: Development Of Chronic Active Antibody-mediated Rejectionmentioning

confidence: 99%

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New treatment for antibody-mediated rejection: interleukin-6 inhibitors

Park,

Kim,

Shin

2024

Clin Transplant Res

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Following kidney transplantation, antibody-mediated rejection (AMR) occurs when the antibodies of the immune system attack the transplanted organ, leading to damage of the kidney tissue. De novo human leukocyte antigen donor-specific antibodies (HLA-DSAs) play a key role in AMR. Current therapeutic approaches include intravenous immunoglobulin, anti-CD20 antibodies, and plasmapheresis. In cases resistant to treatment, proteasome inhibitors and C5 inhibitors may be employed. Nevertheless, a pressing need exists for new medications to improve transplant survival and reduce complications. In the context of AMR, interleukin (IL)-6 is instrumental in the development and maturation of B cells into plasma cells, which then produce HLA-DSAs targeting the allograft. IL-6 inhibitors are currently under investigation and show promise due to the essential role of IL-6 in the immune response; however, additional research is necessary.

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“…Consequently, understanding the natural history of de novo HLA-DSA is valuable for developing new strategies to prevent and treat both AMR and caAMR ( Fig. 1 ) [ 2 , 7 , 8 ].…”

Section: Development Of Chronic Active Antibody-mediated Rejectionmentioning

confidence: 99%

“…To diagnose caAMR, a renal biopsy is typically conducted, on which de novo DSAs can be detected with a probability of 25% to 75%. Furthermore, the detection of tubulitis and/or graft glomerulopathy on the biopsy can inform predictions of graft survival [ 2 , 4 , 8 ].…”

Section: Development Of Chronic Active Antibody-mediated Rejectionmentioning

confidence: 99%

New treatment for antibody-mediated rejection: interleukin-6 inhibitors

Park,

Kim,

Shin

2024

Clin Transplant Res

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“…Intravenous administration of immunoglobulins, apheresis, and pulse of corticosteroids are a part of the treatment strategies in association or not with biologics disrupting B-cells (rituximab), complement (eculizumab) or interleukin 6 (IL-6) pathways (tocilizumab TCZ) [4]. Indeed, some recent studies suggested that targeting IL-6 pathway in particular could be a promising pharmacological strategy in the management of CAMR, given the key role of IL-6 in the regulation of systemic inflammation, the development and maturation of T cells and B cells leading to the synthesis of donor-specific antibody (DSA) [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Early Exposure of Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection to Tocilizumab—A Preliminary Study

Arrivé,

Jacquet,

Gautier-Veyret

et al. 2023

JCM

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Tocilizumab prevents clinical worsening of chronic antibody-mediated rejection (CAMR) of kidney transplant recipients. Optimization of this treatment is necessary. We identified the determinants of early tocilizumab exposure (within the first three months) and investigated the relationship between early plasma tocilizumab exposure and graft function. Patients with CAMR who started treatment with tocilizumab were retrospectively included. Demographic, clinical, and biological determinants of the tocilizumab trough concentration (Cmin) were studied using a linear mixed effect model, and the association between early exposure to tocilizumab (expressed as the sum of Cmin over the three first months (M) of treatment (ΣCmin)) and the urinary albumin-to-creatinine ratio (ACR) determined at M3 and M6 were investigated. Urinary tocilizumab was also measured in seven additional patients. Seventeen patients with 51 tocilizumab Cmin determinations were included. In the multivariate analysis, the ACR and time after tocilizumab initiation were independently associated with the tocilizumab Cmin. The ΣCmin was significantly lower (p = 0.014) for patients with an ACR > 30 mg/mmol at M3 and M6 than for patients with an ACR < 30 mg/mmol. Tocilizumab was detected in urine in only 1/7 patients. This study is the first to suggest that early exposure to tocilizumab may be associated with macroalbuminuria within the first six months in CAMR patients.

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“…Kidney transplantation (Ktx) is the most frequent transplantation worldwide, but transplant survival is limited by a high incidence of late antibody-mediated rejection (AMR) [ 1 , 2 ]. KTRs are regularly and continuously monitored by detection of donor-specific antibodies (DSAs) and transplant biopsies.…”

Section: Introductionmentioning

confidence: 99%

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation

et al. 2022

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Chronic antibody-mediated rejection (AMR) is a key limiting factor for the clinical outcome of a kidney transplantation (Ktx), where early diagnosis and therapeutic intervention is needed. This study describes the identification of the biomarker CXC-motif chemokine ligand (CXCL) 9 as an indicator for AMR and presents a new aptamer-antibody-hybrid lateral flow assay (hybrid-LFA) for detection in urine. Biomarker evaluation included two independent cohorts of kidney transplant recipients (KTRs) from a protocol biopsy program and used subgroup comparisons according to BANFF-classifications. Plasma, urine and biopsy lysate samples were analyzed with a Luminex-based multiplex assay. The CXCL9-specific hybrid-LFA was developed based upon a specific rat antibody immobilized on a nitrocellulose-membrane and the coupling of a CXCL9-binding aptamer to gold nanoparticles. LFA performance was assessed according to receiver operating characteristic (ROC) analysis. Among 15 high-scored biomarkers according to a neural network analysis, significantly higher levels of CXCL9 were found in plasma and urine and biopsy lysates of KTRs with biopsy-proven AMR. The newly developed hybrid-LFA reached a sensitivity and specificity of 71% and an AUC of 0.79 for CXCL9. This point-of-care-test (POCT) improves early diagnosis-making in AMR after Ktx, especially in KTRs with undetermined status of donor-specific HLA-antibodies.

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Anti-Interleukin 6 Therapeutics for Chronic Antibody-Mediated Rejection In Kidney Transplant Recipients

Cited by 3 publications

References 112 publications

New treatment for antibody-mediated rejection: interleukin-6 inhibitors

New treatment for antibody-mediated rejection: interleukin-6 inhibitors

Early Exposure of Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection to Tocilizumab—A Preliminary Study

An Antibody-Aptamer-Hybrid Lateral Flow Assay for Detection of CXCL9 in Antibody-Mediated Rejection after Kidney Transplantation

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