Infections as triggers and complications of systemic lupus erythematosus

Doria, Andrea; Canova, Mariagrazia; Tonon, Michele; Zen, Margherita; Rampudda, E; Bassi, Nicola; Atzeni, Fabiola; Zampieri, Sandra; Ghirardello, Anna

doi:10.1016/j.autrev.2008.07.019

Cited by 166 publications

(113 citation statements)

References 33 publications

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“…Previous studies mainly focused on relationship between endosomal TLRs and autoimmune diseases, such as TLR3, 7 and 9 [26]. [30]. Therefore, to determine how increased expression of TLR2 aggravates the inflammatory response of CD4 + T cells, we measured expression levels of CD40L, CD70, and CD11a.…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of experimental and clinical evidence supports the pivotal role of infections in the induction or exacerbation of SLE. Infections can be responsible for aberrant immune response leading to a loss of tolerance toward native proteins [30]. Therefore, to determine how increased expression of TLR2 aggravates the inflammatory response of CD4 + T cells, we measured expression levels of CD40L, CD70, and CD11a.…”

Section: Discussionmentioning

confidence: 99%

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Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

et al. 2015

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The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage-associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4+ and CD8 + T cells, CD19 + B cells, and CD14 + monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4 + T cells from SLE patients. In vitro stimulation of TLR2 in CD4 + T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL-6, IL-17A, IL-17F, and TNF-α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri-methylation and H4 acetylation levels while downregulated H3K9 tri-methylation level in the IL-17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri-methylation levels in the IL-17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL-17A and IL-17F expression through histone modifications in SLE.Keywords: Histone modification r IL-17 r Systemic lupus erythematosus r T cells r TLR2 IntroductionSystemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease that results in multiple organ damage and diverse clinical manifestations [1]. SLE is characterized by T-cell hyperactivity and B-cell overstimulation. Uncontrolled T-cell activation results in increased secretion of inflammatory cytokines, production of autoantibodies, and aberrant inflamCorrespondence: Prof. Qianjin Lu e-mail: qianlu5860@gmail.com matory response, which contribute to the development of SLE [2]. How T cells become hyperactive during SLE remains to be determined. However, both genetic background and environmental factors are believed to contribute to the development of SLE [3]. A number of epidemiological studies have suggested that onset and flares of SLE are associated with infection [4]. One of the mechanisms whereby invasive microorganisms disrupt host immune system is through the interaction with TLRs, as demonstrated in experimental lupus [5,6]. * These authors contributed equally to this work. Eur. J. Immunol. 2015. 45: 2683-2693 TLRs are membrane-bound proteins referred to as pathogenassociated molecular patterns that belong to innate immune system. Each TLR can recognize a specific set of microbes bearing PAMPs and endogenous damage-associated molecular patterns (DAMPs) [7]. Activation of TLRs can trigger intracellularsignaling cascades and upregulate the expression of inflammatory cytokines [8]. TLR2 is a cell-surface TLR with extracellular recognition domain that can bind with exogenous ligands including lipoproteins, peptidoglycan, lipoteichoic acid, and endogenous DAMPs, such as HSP70 and high mobility group box protei...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

et al. 2015

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“…[101][102][103] Therefore, NET release during For personal use only. on April 29, 2019. by guest www.bloodjournal.org From acute infection may have unintended, long-term side effects that must be considered.…”

Section: Autoimmune and Vasculitic Diseasementioning

confidence: 99%

NETosis: how vital is it?

Yipp¹,

Kubes

2013

Blood

804

793

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In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.

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“…Infections can be a significant complication in certain rheumatic diseases that can lead to hospitalization and death. [2][3][4][5][6][7] One retrospective review of patients with systemic lupus erythematosus (SLE) revealed infection was the second most common cause for hospitalization after a disease flare, with the most common type of infection leading to hospitalization being pneumonia. 2 Another study reviewed a cohort of 1000 patients with SLE from 7 European countries to assess frequency and cause of morbidity and mortality over a 10-year period from 1990 to 2000.…”

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confidence: 99%

Improving Pneumococcal Vaccination in Pediatric Rheumatology Patients

et al. 2015

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BACKGROUND AND OBJECTIVE: Many pediatric rheumatology patients are at increased risk of pneumococcal disease secondary to a deficient immune system and/or immunosuppressive medications. The goal of this study was to improve pneumococcal vaccination rates in this high-risk population.METHODS: Eligible patients included children at least 2 years old and adults with systemic lupus erythematosus and/or currently on immunosuppressive medication. Interventions included a presentation to rheumatology providers, creation of immunization algorithm, previsit planning, placing reminders on clinic forms, and sending reminder e-mails to providers. Chart reviews were performed, and control charts were established to portray change in immunization rates. RESULTS:The preintervention immunization rates for 90 patient visits compared with the immunization rates for the 53-week postintervention period with 1033 patient visits and 299 separate patients were all statistically significant. The 13-valent pneumococcal conjugate vaccine rate increased from 6.7% to 48.4% (x 2 = 58.3, P , .001), 23-valent pneumococcal polysaccharide vaccine rate increased from 8.9% to 28.4% (x 2 = 16.0, P , .001), and combined rate increased from 0% to 23.2% (x 2 = 25.2, P , .001). The improvement was sustained with shifts in the data for each vaccine and combined immunizations for final average rates of 60.9% for 13-valent pneumococcal conjugate vaccine, 39.2% for 23-valent pneumococcal polysaccharide vaccine, and 33.7% for combined.

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Infections as triggers and complications of systemic lupus erythematosus

Cited by 166 publications

References 33 publications

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

NETosis: how vital is it?

Improving Pneumococcal Vaccination in Pediatric Rheumatology Patients

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Infections as triggers and complications of systemic lupus erythematosus

Cited by 166 publications

References 33 publications

Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

NETosis: how vital is it?

Improving Pneumococcal Vaccination in Pediatric Rheumatology Patients

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Product

Resources

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Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications

Increased expression of TLR2 in CD4⁺ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications