Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease

Lood, Christian; Amisten, Stefan; Gullstrand, Birgitta; Jönsen, Andreas; Maria, Andrea De; Truedsson, Lennart; Sturfelt, Gunnar; Erlinge, David; Bengtsson, Anders

doi:10.1182/blood-2010-03-274605

Cited by 199 publications

(147 citation statements)

References 37 publications

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“…The increased IFN␣ production in SLE is seen in serum (41), and an overexpression of type I IFN-regulated genes has been shown in PBMCs (42) and was recently also demonstrated by our group in platelets (43). In the present study, EndoS treatment inhibited all interferogenic effects of the ICs that were tested, and the IC-mediated IFN␣ production from both PDCs and PBMCs was inhibited.…”

Section: Discussionsupporting

confidence: 86%

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

Lood¹,

Maria²,

Lood³

et al. 2012

Arthritis & Rheumatism

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Objective. Systemic lupus erythematosus (SLE) isResults. EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included Fc␥R-mediated phagocytosis by PDCs (P ‫؍‬ 0.001) and subsequent production of IFN␣ (P ‫؍‬ 0.002), IC-induced classical pathway of complement activation (P ‫؍‬ 0.008), chemotaxis, and oxidative burst activity of PMNs (P ‫؍‬ 0.002). EndoS treatment also had a direct effect on the molecular structure of ICs, causing decreased IC size and glycosylation.Conclusion. Our findings indicate that EndoS treatment has prominent effects on several pathogenetically important IC-mediated events, and suggest that EndoS has the potential to be developed as a novel therapy for SLE.

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Section: Discussionsupporting

confidence: 86%

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

Lood¹,

Maria²,

Lood³

et al. 2012

Arthritis & Rheumatism

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“…38 In addition, IRF8 helps to prolong the recruitment of transcription factors to the interferon promoters and thereby amplifies the interferon production. 41 Because interferon-α via several different mechanisms 12,15,[42][43][44][45][46] is important in the development of atherosclerosis in SLE, 16 the IRF8 risk gene variants may contribute to the increased CHD incidence in SLE by affecting the function of the type I interferon system. This includes potential effects on pDCs and also B cells, which are dependent on IRF8 for differentiation and function.…”

Section: Discussionmentioning

confidence: 99%

Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants

Leonard

Svenungsson

Sandling

et al. 2013

Circ Cardiovasc Genet

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Background— Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results— The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association ( P <0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 ( IRF8 ) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r 2 =0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1–6.3), P value 1.9×10 –6 . The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques ( P <0.001) and increased intima-media thickness ( P =0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions— There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.

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“…These molecules in platelets may come from different sources, such as those inherited from megakaryocytes, those absorbed from the plasma, or those generated de novo. With regard to de novo synthesis of molecules in platelets, although platelets are anucleate, they express significant amounts of RNA, including mRNAs (e.g., premature and mature RNA), structural and catalytic RNAs (e.g., ribosomal and tRNA), regulatory RNAs (e.g., microRNA), and noncoding RNA (e.g., anti-sense RNA) (90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105). More recently, it also was revealed that platelets contain all of the molecular machinery to translate mRNA into proteins, and they have the ability to transfer RNA to recipient cells where it can regulate cellular function (101-104).…”

Section: Platelet Transcriptomicsmentioning

confidence: 99%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

179

191

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Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

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Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease

Cited by 199 publications

References 37 publications

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants

Nouvelle Cuisine: Platelets Served with Inflammation

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