Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and increases the level of granulocytes-derived MPs: a possible connection with the effect of LCAP on rheumatoid arthritis

Umekita, Kunihiko; Hidaka, Toshihiko; Ueno, Shiro; Takajo, Ichiro; Yu, Kai; Nagatomo, Yasuhiro; Sawaguchi, Akira; Suganuma, Tatsuo; Okayama, Akira

doi:10.1007/s10165-009-0164-2

Cited by 17 publications

(14 citation statements)

References 34 publications

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“…Recent report showed PE combined with LCAP is effective to induce remission for the patient with steroid, CsA, and PE refractory sJIA . The mechanism of the efficacy of LCAP remains obscure, but removal of activated inflammatory cells, reduction of plasma microparticles are suspected to be effective for MAS . In our patient, PE + LCAP reduced the number of peripheral WBC and serum levels of inflammatory cytokines, as well as previous reports.…”

Section: Discussionsupporting

confidence: 85%

Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome

Kinjo

Hamada

Hirayama

et al. 2017

J of Clinical Apheresis

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Macrophage activation syndrome (MAS) is a life-threating complication of systemic juvenile idiopathic arthritis (s-JIA). Steroid and cyclosporine (CsA) are effective for MAS, but, treatment for steroid-and CsA-resistant patients is still challenging. We report the case of steroid and CsA resistant s-JIA associated MAS misdiagnosed as Kawasaki disease (KD), who was successfully treated with the combination of plasma exchange (PE) and leukocytapheresis (LCAP) followed by plasma diafiltration (PDF). PE 1 LCAP effectively removed proinflammatory cytokines and reduced the number of peripheral white blood cells. Furthermore, PDF also removed proinflammatory cytokines as effectively as PE 1 LCAP. Early diagnosis of s-JIA is necessary to avoid developing MAS. The measurement of serum ferritin and IL-18 levels are useful for differentiating s-JIA from KD. Apheresis therapies are an alternative option to induce remission for severe patients with steroid-or CsA-resistant MAS.

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Section: Discussionsupporting

confidence: 85%

Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome

Kinjo

Hamada

Hirayama

et al. 2017

J of Clinical Apheresis

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“…In this study, we identified for the first time PD-1 expression by EVs and owing to the suggested role of this protein and EVs in RA pathogenesis (32–35), we further characterized the PD-1 expression in EVs in RA patients. Exhausted T cells are associated with chronic inflammatory diseases, including RA (36).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Transfer the Receptor Programmed Death-1 in Rheumatoid Arthritis

et al. 2017

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IntroductionExtracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1).MethodsSynovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients were investigated for PD-1 and other markers of T cell inhibition. EVs were isolated from RA plasma and synovial fluid. In addition, healthy control (HC) and RA PBMCs and SFMCs were cultured to produce EVs. These were isolated and investigated by immunogold electron microscopy (EM) and also co-cultured with lymphocytes and PD-1 negative cells to investigate their functions. Finally, the miRNA expression profiles were assessed in EVs isolated from RA and HC cell cultures.ResultsCells from the RA joint expressed several T cell co-inhibitory receptors, including PD-1, TIM-3, and Tigit. ELISA demonstrated the presence of PD-1 in EVs from RA plasma and synovial fluid. Immunogold EM visualized PD-1 expression by EVs. Co-culturing lymphocytes and the PD-1 negative cell line, U937 with EVs resulted in an induction of PD-1 on these cells. Moreover, EVs from RA PBMCs increased proliferation in lymphocytes when co-cultured with these. All EVs contained miRNAs associated with PD-1 and other markers of T cell inhibition and the content was significantly lower in EVs from RA PBMCs than HC PBMCs. Stimulation of the cells increased the miRNA expression. However, EVs isolated from stimulated RA SFMCs did not change their miRNA expression profile to the same extend.ConclusionEVs carrying both the PD-1 receptor and miRNAs associated with T cell inhibition were present in RA cell cultures. Upon stimulation, these miRNAs failed to be upregulated in EVs from RA SFMCs. This was in line with increased expression of T cell co-inhibitory markers on SFMCs. In conclusion, we suggest EVs to play a significant role in the RA microenvironment, potentially favoring the progression of T cell exhaustion.

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“…Platelets and platelet-derived microparticles have been associated with inflammatory processes of autoimmune disorders including rheumatoid arthritis, systemic lupus erythematosus and sjögren syndrome [14], [22]–[27]. The study of the pathogenesis of these platelet-derived microparticles has increased over the last decade, and multiple mechanisms have been proposed [14], [23], [24], [27].…”

Section: Discussionmentioning

confidence: 99%

“…The study of the pathogenesis of these platelet-derived microparticles has increased over the last decade, and multiple mechanisms have been proposed [14], [23], [24], [27]. Platelet-derived microparticles have been directly involved with leukocyte activation, monocytes in particular, during inflammation [28].…”

Section: Discussionmentioning

confidence: 99%

Erosive Arthritis and Hepatic Granuloma Formation Induced by Peptidoglycan Polysaccharide in Rats Is Aggravated by Prasugrel Treatment

et al. 2013

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Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

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Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and increases the level of granulocytes-derived MPs: a possible connection with the effect of LCAP on rheumatoid arthritis

Cited by 17 publications

References 34 publications

Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome

Role of plasma exchange, leukocytapheresis, and plasma diafiltration in management of refractory macrophage activation syndrome

Extracellular Vesicles Transfer the Receptor Programmed Death-1 in Rheumatoid Arthritis

Erosive Arthritis and Hepatic Granuloma Formation Induced by Peptidoglycan Polysaccharide in Rats Is Aggravated by Prasugrel Treatment

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