Adenosine deaminase deficiency: a review

Flinn, Aisling M.; Gennery, Andrew R.

doi:10.1186/s13023-018-0807-5

Cited by 161 publications

(110 citation statements)

References 51 publications

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“…Other enzymes that have been described for use in enzyme replacement therapy are phenylalanine hydroxylase (for phenylketonuria [47][48][49][50]), adenosine deaminase (for severe combined immunodeficiency with impaired humoral and cellular immune response [27,[51][52][53][54][55]) and thymidine phosphorylase (for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) [56,57]). For adenosine deaminase, successful long-term (9 years) use of the adenosine deaminase-loaded RBCs in the clinic has been described [58].…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

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Section: Enzyme Replacement Therapymentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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“…Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by‐products, most potently affecting lymphocytes, but other manifestations include skeletal abnormalities, neurodevelopmental affects, and pulmonary manifestations associated with pulmonary‐alveolar proteinosis . The major consequences of ADA mutations are severe depletion of T and B lymphocytes and NK cells.…”

Section: Monogenic Forms Of Inflammatory Bowel Diseasementioning

confidence: 99%

“…Impaired V(D)J recombination results in an emergence of an oligoclonal T-cell repertoire, which indicates that the thymic selection in patients with Omenn syndrome is restricted to the T cell in which recombinase activity is sufficient to generate a functional TCR 97. Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, but other manifestations include skeletal abnormalities, neurodevelopmental affects, and pulmonary manifestations associated with pulmonary-alveolar proteinosis 98. The major consequences of ADA mutations are severe depletion of T and B lymphocytes and NK cells.…”

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confidence: 99%

Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms

Pázmándi

Kalinichenko

Ardy

et al. 2018

Immunological Reviews

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Summary Rare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early‐onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early‐onset IBD (VEO‐IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections. As for other human diseases, it is likely that adult‐onset diseases may represent complex diseases integrating the effects of host genetic susceptibility and environmental triggers. Comparison of adult‐onset IBD and VEO‐IBD thus provides beautiful models to investigate the relationship between monogenic and multifactorial/polygenic diseases. This review discusses the present and novel findings regarding monogenic IBD as well as key questions and future directions of IBD research.

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“…Severe combined immunodeficiency due to adenosine deaminase deficiency is a rare autosomal recessive disease (ADA-SCID, OMIM # 102,700) caused by mutations in the gene encoding the enzyme ADA type 1, resulting in impairment of the purine salvage pathway [1][2][3]. This defect in purine metabolism primarily affects lymphocyte development and function resulting in varying degrees of immune deficiency [4].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies demonstrate that ADA-SCID is a systemic disease, and thanks to improved survival, an increasing number of non-immune manifestations are being recognized and reported [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Urogenital Abnormalities in Adenosine Deaminase Deficiency

et al. 2020

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Background Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients.Methods We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000-2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients' follow-up. Results and Discussion We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5-4% described in healthy children; acquired, 16% in our sample, 1-3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. Conclusion In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients' quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any

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Adenosine deaminase deficiency: a review

Cited by 161 publications

References 51 publications

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Erythrocytes as Carriers: From Drug Delivery to Biosensors

Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms

Urogenital Abnormalities in Adenosine Deaminase Deficiency

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