Platelets and IgE: Shaping the Innate Immune Response in Systemic Lupus Erythematosus

Brilland, Benoît; Scherlinger, Marc; Khoryati, Liliane; Goret, Julien; Duffau, Pierre; Lazaro, Estibaliz; Charrier, Manon; Guillotin, Vivien; Richez, Christophe; Blanco, Patrick

doi:10.1007/s12016-019-08744-x

Cited by 15 publications

(5 citation statements)

References 164 publications

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“…Activation of basophils by ICs with autoreactive IgE amplifies autoantibody production [ 17 ]. Non-autoreactive IgE is negatively associated with the lupus erythematosus activity index (SLEDAI) and prevents the release of IFN by pDC [ 18 ]. Studies have revealed that 30%-50% of SLE patients with autoreactive IgE are mainly directed against dsDNA, Ro/SSA, La/SSB, and Sm [ 2 , 19 ], and anti-dsDNA IgE was discovered in all lupus subtypes [ 16 ] and have been linked with the activity of SLE disease [ 20 ] and kidney involvement.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have revealed that 30%-50% of SLE patients with autoreactive IgE are mainly directed against dsDNA, Ro/SSA, La/SSB, and Sm [ 2 , 19 ], and anti-dsDNA IgE was discovered in all lupus subtypes [ 16 ] and have been linked with the activity of SLE disease [ 20 ] and kidney involvement. Reducing the levels of autoreactive IgE and inhibiting their receptors or increasing non-autoreactive IgE are considered promising therapeutic objectives in the management of SLE [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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Lupus Nephritis in an Adolescent Girl With Hyper-Immunoglobulin E

Alahmadi¹,

El-Desoky²,

Zahrani³

et al. 2023

Cureus

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We report the case of an adolescent girl with frequent hospital admissions for severe eczematous skin rashes with recurrent epistaxis and chest infections. Investigations revealed persistent severely elevated serum total immunoglobulin E (IgE) levels but normal levels of other immunoglobulins, suggesting hyper-IgE syndrome. The first skin biopsy revealed superficial dermatophytic dermatitis (tinea corpora). Another biopsy performed after six months revealed a prominent basement membrane with dermal mucin, suggesting an underlying autoimmune disease. Her condition was complicated by proteinuria, hematuria, hypertension, and edema. A kidney biopsy revealed class IV lupus nephritis, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS). Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, she was diagnosed with systemic lupus erythematosus (SLE). She was first administered with intravenous pulse methylprednisolone (600 mg/m 2 ) for three consecutive days, followed by oral prednisolone (40 mg/m 2 ) daily, mycophenolate mofetil tablets (600 mg/m 2 /dose) twice daily, hydroxychloroquine (200 mg) once daily, and three classes of antihypertensive medications. She maintained normal renal functions with no lupus morbidity for 24 months, then rapidly progressed to end-stage kidney disease, and was then started on three to four sessions of regular hemodialysis per week.Hyper-IgE is known to be a marker of immune dysregulation as it facilitates the generation of immune complexes (ICs) that mediate lupus nephritis and juvenile SLE.Regardless of the different factors that are impacting the production of IgE, the present case illustrated that juvenile patients with SLE may have increased IgE levels, indicating that higher IgE levels might have a role in lupus pathogenesis and prognosis. The mechanisms regarding the increased levels of IgE in subjects with lupus need further investigation. Further studies are thus required to assess the incidence, prognosis, and possible new specific management for hyper-IgE in juvenile SLE.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lupus Nephritis in an Adolescent Girl With Hyper-Immunoglobulin E

Alahmadi¹,

El-Desoky²,

Zahrani³

et al. 2023

Cureus

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“…After immune in ltration analyses, we noticed that LIAS expression was highly correlated with the in ltration of immune cells, such as iTreg cells, platelet, Th1 cells, Th2 cells, Tfh cells, NK cells, CD4 T cells, CD8 T cells, neutrophil, monocytes, macrophages and so on. Abundance of studies have reported that these cells were associated with the pathology and development of SLE [43][44][45] . Thus, we hypothesized that LIAS as an essential cuproptosis-mediated gene may involve in regulating the immune cells in ltration to lead to the occurrence and advancement of SLE.…”

Section: Discussionmentioning

confidence: 99%

Exploring the role of LIAS-related cuproptosis in systemic lupus erythematosus

Zhang

et al. 2023

Preprint

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Background Cuproptosis is a novel mode of cell death, which is strongly related to energy metabolism in mitochondria and regulated by protein lipoylation. Currently, the molecular mechanisms of cuproptosis-related genes (CRGs) involved in systemic lupus erythematosus (SLE) largely remained unclear, our study is aimed to explore the mechanisms of cuproptosis and CRGs involved in SLE. Methods Bulk RNA-seq datasets were collected to display the expressions of CRGs in peripheral blood mononuclear cells (PBMCs) of SLE and healthy individuals, then ROC analysis was used to establish the diagnostic models of CRGs. Next, the immune infiltration analyses were applied to reveal the difference of immune cells infiltration in LIAS-low and LIAS-high group. Additionally, WGCNA analysis was performed to find the gene modules significantly corelated with the LIAS expression level. We also performed the functional enrichment analyses for LIAS-related gene modules to determine the potential pathways involved in the development of SLE. Finally, scRNA-seq dataset was used to cluster immune cell subsets, reveal the activated pathways, and study cell-cell interactions in LIAS-low and LIAS-high cells. Result We found CDKN2A was significantly increased and LIAS was significantly decreased in SLE patients compared with healthy individuals. The AUC score showed that LIAS had a great diagnostic value than other CRGs. Additionally, the results of immune infiltration analyses showed that immune cells proportion were diverse in LIAS-low and LIAS-high samples. The gene sets related to LIAS expression level were involved in dephosphorylation of JAK1 by SHP1, phosphorylation of STAT2, cytokine signaling in immune system, expression of interferon-alpha and beta, inhibition of JAK kinase activity by SOCS1/3 and so on. Finally, the results of cell-cell communication showed that CCL- (CCL5 + CCR1) and ANNEXIN- (ANXA1 + FPR1) might play an essential role in the communication network between LIAS-low and LIAS-high cells. Conclusions Above findings inferred that LIAS-mediated cuproptosis might involve in a comprehensive cellular and molecular mechanism to cause the occurrence and development of SLE.

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“…Our focus on red blood cell and platelet cytopenias is relevant as both of these cellular subtypes are actively involved in the systemic inflammation that occurs in cSLE. 26–31 Recent blood transcriptome analyses of cSLE patients found a strong correlation between neutrophil signature and the presence of LN. 24 Similarly, another gene expression study of adult and pediatric SLE patients found neutrophil-driven clusters to be associated with an increased risk of proliferative LN.…”

Section: Discussionmentioning

confidence: 99%

Impact of autoimmune cytopenias on severity of childhood-onset systemic lupus erythematosus: A single-center retrospective cohort study

Ogbu

Chandrakasan

Rouster‐Stevens

et al. 2020

Lupus

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Objective To assess whether children with autoimmune cytopenias prior to or at diagnosis of systemic lupus erythematosus (cSLE), differ phenotypically from other cSLE patients; and have a lower risk and severity of lupus nephritis (LN) as observed in prior adult studies. To assess the effect of prior immune therapy for autoimmune cytopenias on 2-year risk of LN. Methods This was a retrospective cohort study of incident cSLE cases. We included patients aged less than 17 years at diagnosis. We excluded patients with LN at cSLE diagnosis. Our follow-up period was 2 years. We defined autoimmune cytopenias as either autoimmune hemolytic anemia, immune thrombocytopenia or Evan’s syndrome. Results Forty-three (33%) of the 130 patients had autoimmune cytopenias before or at cSLE diagnosis. Those with autoimmune cytopenias had significantly more neuropsychiatric symptoms and higher mean ESR but less arthritis, malar rash and myositis versus those without autoimmune cytopenias. They had lower 2-year incidence proportion of LN compared to other cSLE patients (7% vs 15%). Of the 16 patients who developed LN, those with autoimmune cytopenias had mostly class V (2 of 3 patients) versus mostly class III and IV in those without autoimmune cytopenias (6 of 12 patients). None of the 13 patients pre-treated for autoimmune cytopenias developed LN. Conclusion Patients with autoimmune cytopenias before or at cSLE diagnosis have intriguing differences from other cSLE patients. They may represent a unique sub-type of cSLE patients and should be further explored.

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Platelets and IgE: Shaping the Innate Immune Response in Systemic Lupus Erythematosus

Cited by 15 publications

References 164 publications

Lupus Nephritis in an Adolescent Girl With Hyper-Immunoglobulin E

Lupus Nephritis in an Adolescent Girl With Hyper-Immunoglobulin E

Exploring the role of LIAS-related cuproptosis in systemic lupus erythematosus

Impact of autoimmune cytopenias on severity of childhood-onset systemic lupus erythematosus: A single-center retrospective cohort study

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