Granulocyte and Monocyte Adsorption Apheresis (GCAP) for Refractory Skin Diseases Caused by Activated Neutrophils and Psoriatic Arthritis: Evidence that GCAP Removes Mac‐1‐Expressing Neutrophils

Kanekura, Takuro; Hiraishi, Katsuya; Kikuchi, Kôichi; Maruyama, Ikuro; Kanzaki, Tamotsu

doi:10.1111/j.1744-9987.2006.00369.x

Cited by 44 publications

(82 citation statements)

References 23 publications

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“…The appearance of similar granulocyte abnormalities in individuals with defects in adjacent steps of the cholesterol synthesis pathway could be coincidental. However, granulocyte/neutrophil-rich pathology is also characteristic of psoriasis and psoriatic arthritis, and our findings suggest a direct association between demethylation of MASs and innate immunity (38,39). It is also intriguing to speculate that the mild elevation of 4,4′-dimethylsterols seen in the patient's father could be relevant to his history of early-onset inflammatory joint disease.…”

Section: Figurementioning

confidence: 59%

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

He¹,

Kratz²,

Michel³

et al. 2011

J. Clin. Invest.

100

111

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Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase-like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β (LXRα and LXRβ), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined. IntroductionCholesterol is a key component of cell membranes and lipid rafts and is the immediate precursor of steroids, vitamin D, and bile acids. Many disorders of cholesterol synthesis share common clinical features, such as abnormal morphogenesis, growth delay, and psychomotor disabilities (1). However, there are also striking differences suggesting that reduced de novo cholesterol synthesis per se may not primarily underlie some of the symptoms, including cataracts as well as skin and immune system abnormalities. Rather, recent studies implicate the accumulation of pre-cholesterol sterols and the replacement of cholesterol with some of these sterols in lipid rafts as playing a key role in the underlying pathophysiology (2). The meiosis-activating sterols (MASs) were the first group of cholesterol biogenesis intermediates that were found to have important extrahepatic functions in mammals. These include 4,4′-dimethyl-5α-cholesta-8,24-dien-3β-ol (testis meiosis-activating sterol [T-MAS]), 4,4′-dimethyl-5α-cholesta-8,14,24-trien-3β-ol (follicular fluid meiosis-activating sterols [FF-MASs]), and zymosterol. They are found in high concentration in testis and ovary and play roles in oocyte maturation and meiosis activation. The function of the MASs outside the reproductive organs is not well studied. FF-MAS is also a ligand for liver X receptors (LXRs) (3). LXR signaling is known to regulate crosstalk between inflammatory and cholesterol metabolism,

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Section: Figurementioning

confidence: 59%

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

He¹,

Kratz²,

Michel³

et al. 2011

J. Clin. Invest.

100

111

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“…This approach is already used as a therapeutic strategy for other inflammatory diseases. Indeed, some extracorporeal apheresis systems (for example, cellulose acetate beads) have been developed to remove activated monocytes and granulocytes in order to treat specific refractory and inflammatory diseases associated with leukocytes such as ulcerative colitis, neutrophilic dermatosis and psoriatic arthritis [27-29]. More recently, Humes et al .…”

Section: Discussionmentioning

confidence: 99%

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study

et al. 2013

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“…The CA beads in the column activate and adsorb complement component iC3b, a ligand for Mac‐1 that is a cell‐surface adhesive molecule expressed on activated granulocytes and monocytes. Based on these facts, we previously demonstrated that the column selectively traps activated granulocytes by binding Mac‐1 expressed on the granulocytes to iC3b on the beads . It was initially approved for the treatment of ulcerative colitis .…”

Section: Discussionmentioning

confidence: 95%

“…Based on this and previous experience and in vitro observations, we posit that GMA is a useful treatment modality for refractory skin diseases attributable to activated granulocytes. Our favorable experience in the present case suggests that GMA is safe and useful in pregnant and non‐pregnant patients.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte and monocyte adsorption apheresis for Behçet's disease in a pregnant woman

Higashi

Shimokawa

Kawai

et al. 2013

The Journal of Dermatology

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Granulocyte and Monocyte Adsorption Apheresis (GCAP) for Refractory Skin Diseases Caused by Activated Neutrophils and Psoriatic Arthritis: Evidence that GCAP Removes Mac‐1‐Expressing Neutrophils

Cited by 44 publications

References 23 publications

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study

Granulocyte and monocyte adsorption apheresis for Behçet's disease in a pregnant woman

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