A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

Banasik, Mirosław; Kościelska‐Kasprzak, Katarzyna; Márta, Mészáros; Bartoszek, Dorota; Żabińska, Marcelina; Boratyńska, Maria; Kamińska, Dorota; Mazanowska, Oktawia; Zmonarski, Sławomir; Krajewska, Magdalena; Hałoń, Agnieszka; Dawiskiba, Tomasz; Nowakowska, Beata; Klinger, Marian

doi:10.1016/j.transproceed.2014.09.028

Cited by 3 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,18 Brain-dead donors also differ from living donors (LDs) in terms of DAMP generation, e.g., by more intensive release of HMGB1 by renal tubular cells 6,25 and of IL1β, TNF-α, IL12, and IL6 by local monocytes/macrophages and mature dendritic cells (mDCs) located inside the kidney. 7,15 Several factors may contribute to damage of endothelia, e.g., anti-human leukocyte antibodies (HLA), 34 non-HLA antibodies 4,35 or shear stress causing shedding of glycocalyces with a subsequent increase in permeability. 8,31 Cellular stress induces an increase in complement activation with C3a (and C5a) generation 15 by resident cells and infiltrating leukocytes.…”

Section: Innate Immunity: From Brain Death To Reperfusion Injurymentioning

confidence: 99%

“…25 The precise cause of CAI remains unclear, but appears to be related to pathological changes due to organ preservation, IRI prior to and after organ implantation, 17 drug-related nephrotoxicity (e.g., calcineurin inhibitors), and chronic immune injury 25 with, e.g., anti-endothelial cell antibodies, anti-angiotensin II type 1 receptor (anti-AT1R) antibodies, anti-endothelin receptor antibodies (anti-ETAR), 4 non-HLA antibodies, 4,35 or anti-HLA antibodies (in our observation, about 50% patients with anti-HLA antibodies return to dialysis). 35 A transplanted kidney undergoing CAI releases DAMPs of varying intensity. Several molecules are implicated in this process, including fragments of nucleic acids, extracellular matrices (hyaluronic acid, fibronectin, heparin sulfate), HMGB1, fibrinogen, uric acid crystals, heat shock proteins, and fibrin.…”

Section: Chronic Graft Injuriesmentioning

confidence: 99%

See 1 more Smart Citation

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

View full text Add to dashboard Cite

Krajewska M. The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells. AbstractThe innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

show abstract

Section: Innate Immunity: From Brain Death To Reperfusion Injurymentioning

confidence: 99%

Section: Chronic Graft Injuriesmentioning

confidence: 99%

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

View full text Add to dashboard Cite

show abstract

“…Late AMR has been recognized as a clinically distinct entity from early AMR that is resistant to treatment and associated with poor allograft survival [18–22]. Previous authors have noted stabilization or improvement of late AMR with bortezomib [21, 26, 28, 29], but our case series is the first to report this finding in a cohort of mainly high risk adolescents.…”

Section: Discussionmentioning

confidence: 56%

“…In vitro studies have shown that bortezomib treated lymphocytes [47] and multiple myeloma cells [48] preferentially reduce HLA Class I expression and decrease stimulation for continued Class I antibody production [47]. The effect of bortezomib on cell surface expression of HLA Class I but not Class II may explain why this therapy has not produced dramatic recovery of renal function or biopsy findings in many patients with late AMR associated with HLA Class II DSAs [22, 49]. Interestingly, patients treated with bortezomib have shown modest improvement in eGFR despite the persistence of DSAs, which is consistent with our findings [25, 26].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

et al. 2016

View full text Add to dashboard Cite

Background Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d+ AMR in pediatric kidney transplant patients. Methods We examined 7 patients with treatment refractory C4d+ AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and antimetabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy. Results Seven patients (86% male, 86% with ≥6/8 HLA mismatch, and 14% with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1–145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86%), the mean pre-bortezomib eGFR was 42 mls/min/1.73 m2 and the mean 1 year post-bortezomib eGFR was 53 mls/min/1.73m2. Five of 7 (71%) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for Class I than Class II. Conclusions Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d+ AMR.

show abstract

Preemptive HLA Antibody Screening Prior to Episodic Transplant Renal Biopsy Enables Early Diagnosis and Therapeutic Response in Asymptomatic Chronically Active Antibody-Related Rejection: A Case Report

Kasuno

Nishimori

Yokoi

et al. 2020

Transplantation Proceedings

View full text Add to dashboard Cite

A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

Cited by 3 publications

References 30 publications

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

Preemptive HLA Antibody Screening Prior to Episodic Transplant Renal Biopsy Enables Early Diagnosis and Therapeutic Response in Asymptomatic Chronically Active Antibody-Related Rejection: A Case Report

Contact Info

Product

Resources

About