Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation

Muñoz-Herrera, Claudia M.; Gutiérrez‐Bautista, Juan Francisco; Nevot, López

doi:10.3390/jcm12062335

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…After kidney transplantation, recipients can develop donor-specific antibodies (DSA), including anti-ABO and anti-HLA as part of their humoral immunity. These immunoglobulins bind to endothelial cells during AMR, initiating the complement classical pathway [128]. In turn, anaphylatoxins potentiate inflammation, whereas MAC hurts the integrity of blood vessels because of CDC [129].…”

Section: Complement and Kidney Transplantationmentioning

confidence: 99%

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma

Lasorsa,

Rutigliano,

Milella

et al. 2023

IJMS

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The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.

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Section: Complement and Kidney Transplantationmentioning

confidence: 99%

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma

Lasorsa,

Rutigliano,

Milella

et al. 2023

IJMS

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“…Over the last decade, the identification of anti-HLA DSAs and their characteristics has improved due to the use of solid-phase assay technology, particularly single antigen bead (SAB) testing [2]. In addition, the destructive effect of anti-HLA DSAs is determined by antibody characteristics including class, specificity, mean fluorescent intensity (MFI), complement-biding ability, and IgG subclass [3,4].…”

Section: Introductionmentioning

confidence: 99%

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

Gniewkiewicz

Czerwińska

Zielniok

et al. 2023

JCM

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The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041–17.431, p = 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483–13.520, p = 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139–8.676, p = 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes.

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The future of complement therapeutics

Kolev,

Rao,

Yeh

et al. 2024

Explor Immunol

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Complement is both evolutionary and scientifically old. It predates the adaptive immunity by some 600 million years and was first described in 1905 by Jules Bordet and Paul Ehrlich. For the most of its, the existence complement system has been ignored by most scientists and clinicians due to the perception of it being complicated and its relevance for the pathogenesis of human disease being unclear. With the recent US Food and Drug Administration (FDA) approvals of pegcetacoplan for both paroxysmal nocturnal haemoglobinuria (PNH) and geographic atrophy (GA), avacincaptad pegol for GA and iptacopan and danicopan for PNH, we are at a crucial juncture for complement-targeting therapies. A number of companies and academic institutions are developing next-generation complement therapies, which is resulting in an increasingly competitive landscape. If one looks at the serum complement cascade, all 3 pathways now have biotechnology or pharmaceutical industry players with 1 or multiple clinical-stage inhibitors that are expected to be FDA approved within the next few years. Furthermore, with the limited number of clinically validated targets in complement-mediated disease, the competition in this space is set to further intensify in the coming years. In this review, we will discuss the timeline of the academic discoveries that led to the development of the current crop of FDA-approved complement therapeutics. We follow with a discussion of an increasingly crowded complement therapy space and of the scientific advances that have emerged in recent two decades underpinning future innovation, including advances in our understanding of complement biology, such as local and intracellular complement, emerging complement targets, combinational approaches of complement and non-complement therapeutics to unlock new disease indications and new technologies such as gene therapy. We will also give a comprehensive overview of the gene therapy landscape and how it can be utilized to target complement dysregulation.

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Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation

Cited by 3 publications

References 43 publications

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

The future of complement therapeutics

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