Altered Expression Pattern of CD55 and CD59 on Red Blood Cells in Anemia of Chronic Kidney Disease

Al-Faris, Lama; Al-Humood, Salah; Behbehani, Fatma; Sallam, Husam

doi:10.1159/000481823

Cited by 12 publications

(10 citation statements)

References 25 publications

(33 reference statements)

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“…The presence of uremic inhibitors of erythropoiesis, shortened erythrocyte survival, excessive bleeding, and iron deficiency have all been proposed as factors contributing to the anemia of chronic renal failure. In addition, deficiency of complement regulatory proteins may be another factor in anemia of CKD 12…”

Section: Discussionmentioning

confidence: 99%

<p>Expression levels of complement regulatory proteins (CD35, CD55 and CD59) on peripheral blood cells of patients with chronic kidney disease</p>

Eldewi¹,

Alhabibi²,

Sayed³

et al. 2019

IJGM

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BackgroundAltered regulation of the complement system is associated with multiple kidney diseases. CD35, CD55 and CD59 regulate the complement system, and changes in their expression have previously been linked with kidney disease. This study assessed whether changes in the expression levels of these proteins are associated specifically with chronic kidney disease (CKD) to understand its pathogenesis.Materials and methodsSixty CKD patients and 60 age-matched controls were enrolled and divided into two groups: Group I (n=30 pediatric patients and n=30 controls) and Group II (n=30 adult patients and n=30 controls). The expression of CD35, CD55 and CD59 on peripheral blood cells was evaluated by flow cytometry as the proportion of positive cells expressing the marker and mean fluorescence intensity (MFI), also the relation of these markers to the stage of CKD was also evaluated.ResultsPediatric and adult CKD patients had significantly lower proportion of erythrocytes expressing CD35, CD55 and CD59 than healthy controls (P<0.001). In pediatric CKD patients, there was no significant difference in the three studied markers on neutrophils, lymphocytes and monocytes. The changes in expression of CD35, CD55 and CD59 on leukocytes were more pronounced in adult patients, who had lower proportion of CD59-positive neutrophils, CD35- and CD59-positive lymphocytes, and CD59-positive monocytes, as well as lower expression of CD59 on neutrophils and monocytes than adult controls (P<0.001, P=0.019, P<0.001, P=0.026, P<0.001 and P=0.003, respectively). The eGFR directly correlated with the proportion of positivity of some of those markers on peripheral leukocytes while there was inverse correlation between the disease stage and the same markers.ConclusionThere are alterations in the patterns of expression of complement regulatory proteins CD35, CD55 and CD59 on peripheral blood cells of patients with CKD compared with healthy controls.

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Section: Discussionmentioning

confidence: 99%

<p>Expression levels of complement regulatory proteins (CD35, CD55 and CD59) on peripheral blood cells of patients with chronic kidney disease</p>

Eldewi¹,

Alhabibi²,

Sayed³

et al. 2019

IJGM

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“…Altered expression of CD55 and CD59 has also been observed in CKD patients [34]. In this context, Lama Al-Faris et al have evaluated the expression pattern of CD55 and CD59 proteins on erythrocyte of patients with CKD [2,35].…”

Section: Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

“…Apart from PNH, literature underlines the presence of a cellular PNH-like phenotype in several clinical conditions, including autoimmune diseases, diabetes mellitus, HIV infectious and treatment regimens immunotherapy-based [2]. There is yet a lack of indepth knowledge regarding the development in terms of the PNH-like cellular phenotype, however it is important to identify and distinguish these from the effective PNH clone.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic risk in paroxysmal nocturnal hemoglobinuria-like (PNH-like) phenotype

Carlisi

Mancuso

Caimi

et al. 2021

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The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients.

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“…Increased hemolysis was confirmed in patients with high levels of CD55- and CD59 deficient RBCs. The underlying cause of CKD in these patients was not reported, making it difficult to speculate on the mechanisms involved ( 100 ). Furthermore, VTN has been shown to be upregulated in chronic kidney disease.…”

Section: The Role Of Complement Regulators In Pathologiesmentioning

confidence: 99%

Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease

Mourik

Jongerius

2020

Front. Immunol.

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The complement system is an important part of the innate immune system, providing a strong defense against pathogens and removing apoptotic cells and immune complexes. Due to its strength, it is important that healthy human cells are protected against damage induced by the complement system. To be protected from complement, each cell type relies on a specific combination of both soluble and membrane-bound regulators. Their importance is indicated by the amount of pathologies associated with abnormalities in these complement regulators. Here, we will discuss the current knowledge on complement regulatory protein polymorphisms and expression levels together with their link to disease. These diseases often result in red blood cell destruction or occur in the eye, kidney or brain, which are tissues known for aberrant complement activity or regulation. In addition, complement regulators have also been associated with different types of cancer, although their mechanisms here have not been elucidated yet. In most of these pathologies, treatments are limited and do not prevent the complement system from attacking host cells, but rather fight the consequences of the complement-mediated damage, using for example blood transfusions in anemic patients. Currently only few drugs targeting the complement system are used in the clinic. With further demand for therapeutics rising linked to the wide range of complement-mediated disease we should broaden our horizon towards treatments that can actually protect the host cells against complement. Here, we will discuss the latest insights on how complement regulators can benefit therapeutics. Such therapeutics are currently being developed extensively, and can be categorized into full-length complement regulators, engineered complement system regulators and antibodies targeting complement regulators. In conclusion, this review provides an overview of the complement regulatory proteins and their links to disease, together with their potential in the development of novel therapeutics.

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Altered Expression Pattern of CD55 and CD59 on Red Blood Cells in Anemia of Chronic Kidney Disease

Cited by 12 publications

References 25 publications

<p>Expression levels of complement regulatory proteins (CD35, CD55 and CD59) on peripheral blood cells of patients with chronic kidney disease</p>

<p>Expression levels of complement regulatory proteins (CD35, CD55 and CD59) on peripheral blood cells of patients with chronic kidney disease</p>

Thrombotic risk in paroxysmal nocturnal hemoglobinuria-like (PNH-like) phenotype

Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease

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