CD59: Biological function and its potential for drug target action

Sarmoko,; Ramadhanti, Monica; Zulkepli, Nur Ayunie

doi:10.1016/j.genrep.2023.101772

Cited by 2 publications

(1 citation statement)

References 41 publications

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“…Another potential alternative is to employ the therapeutic anti-complement antibodies eculizumab and ravulizumab, which are primarily used to treat paroxysomal nocturnal hemoglobunuria, a disorder in which the red blood cells exhibit a deficiency of CD59 and so are vulnerable to MAC. The antibodies are generally well tolerated, but increase the risk of meningococcal infections, so patients must be vaccinated prior to treatment [ 65 , 66 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

CD59 Protects Primary Human Cerebrovascular Smooth Muscle Cells from Cytolytic Membrane Attack Complex

Whinnery,

Nie,

Boskovic

et al. 2024

Brain Sciences

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Cerebral amyloid angiopathy is characterized by a weakening of the small- and medium-sized cerebral arteries, as their smooth muscle cells are progressively replaced with acellular amyloid β, increasing vessel fragility and vulnerability to microhemorrhage. In this context, an aberrant overactivation of the complement system would further aggravate this process. The surface protein CD59 protects most cells from complement-induced cytotoxicity, but expression levels can fluctuate due to disease and varying cell types. The degree to which CD59 protects human cerebral vascular smooth muscle (HCSM) cells from complement-induced cytotoxicity has not yet been determined. To address this shortcoming, we selectively blocked the activity of HCSM-expressed CD59 with an antibody, and challenged the cells with complement, then measured cellular viability. Unblocked HCSM cells proved resistant to all tested concentrations of complement, and this resistance decreased progressively with increasing concentrations of anti-CD59 antibody. Complete CD59 blockage, however, did not result in a total loss of cellular viability, suggesting that additional factors may have some protective functions. Taken together, this implies that CD59 plays a predominant role in HCSM cellular protection against complement-induced cytotoxicity. The overexpression of CD59 could be an effective means of protecting these cells from excessive complement system activity, with consequent reductions in the incidence of microhemorrhage. The precise extent to which cellular repair mechanisms and other complement repair proteins contribute to this resistance has yet to be fully elucidated.

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Section: Discussionmentioning

confidence: 99%

CD59 Protects Primary Human Cerebrovascular Smooth Muscle Cells from Cytolytic Membrane Attack Complex

Whinnery,

Nie,

Boskovic

et al. 2024

Brain Sciences

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Semi-supervised Omics Factor Analysis (SOFA) disentangles known sources of variation from latent factors in multi-omics data

Capraz,

Vöhringer,

Huber

2024

Preprint

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Group Factor Analysis is a family of methods for representing patterns of correlation between features in tabular data1. Argelaguet et al. identify latent factors within and across modalities2. Often, some factors align with known covariates, and currently, such alignment is done post hoc. We present Semi-supervised Omics Factor Analysis (SOFA), a method that incorporates known sources of variation into the model and focuses the latent factor discovery on novel sources of variation. We apply it to a pan-gynecologic multi-omics data set from The Cancer Genome Atlas (TCGA), where we guide the model with cancer type labels and discover an independent factor representing an immune infiltration vs proliferation transition axis. The inferred factor is predictive of treatment outcomes. We further use SOFA to identify microglial subpopulations during adolescence associated with cell migration and inflammatory response in a single-cell multi-omics data set (RNA- and ATAC-seq) from the human cerebral cortex. SOFA simplifies the discovery of novel patterns and structures in multi-omics data.

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CD59: Biological function and its potential for drug target action

Cited by 2 publications

References 41 publications

CD59 Protects Primary Human Cerebrovascular Smooth Muscle Cells from Cytolytic Membrane Attack Complex

CD59 Protects Primary Human Cerebrovascular Smooth Muscle Cells from Cytolytic Membrane Attack Complex

Semi-supervised Omics Factor Analysis (SOFA) disentangles known sources of variation from latent factors in multi-omics data

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