A T cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus

Grammatikos, Alexandros P.; Kyttaris, Vasileios C.; Kis-Tóth, Katalin; Fitzgerald, Lisa M.; Devlin, Amy; Finnell, M.; Tsokos, George C.

doi:10.1016/j.clim.2013.12.002

Cited by 31 publications

(24 citation statements)

References 36 publications

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“…However, apart from the anti-virus function, OAS family proteins may be also related to SLE pathogenesis. Grammatikos et al suggested that combining the expression levels of OAS2, CD70, and IL10 in T cells can be used for diagnosis and monitoring of disease activity in SLE patients (14)(15)(16). A ''T-cell score'', which was created with the three gene panel, was significantly higher in SLE patients than in the healthy control group and correlated significantly with dsDNA, PGA, SLEDAI, and ESR levels (14).…”

Section: Discussionmentioning

confidence: 99%

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Gao¹,

Tan²,

Luo³

2020

Braz J Med Biol Res

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Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an aberrant activation of immune cells partly due to the dysfunction of cytokines such as type I interferons (IFNs). Long non-coding RNA MALAT1 has been found to play a pathogenic role in SLE; however, the underlying mechanisms are still poorly understood. Bioinformatics analysis showed the up-regulation of type I IFN downstream effectors OAS2, OAS3, and OASL (OAS-like) in CD4 + T cells, CD19 + B cells, and CD33 + myeloid cells in patients with active SLE compared to healthy participants. In this study, peripheral blood mononuclear cells (PBMCs), CD19 + B, and CD4 + T cells were isolated from active SLE patients and healthy participants. PCR was performed to quantify MALAT1, OAS2, OAS3, and OASL expression in immune cells. MALAT1, OAS2, OAS3, and OASL were knocked down in CD4 + T cells to investigate the regulatory effect of MALAT1 on the effectors and their involvement in type I IFNs-mediated inflammation. Results showed higher OAS2, OAS3, and OASL expression in active SLE patients. MALAT1 expression was positively correlated to OAS2, OAS3, and OASL expression in CD19 + B or CD4 + T cells. MALAT1 knockdown decreased OAS2, OAS3, and OASL expression. Treatment with IFN-a-2a increased the expression of TNF-a, IL-1b, and IFN-a in CD4 + T cells. However, knockdown of MALAT1, OAS2, OAS3, and OASL alone inhibited the effect of IFN-a-2a on TNF-a and IL-1b. This study suggested the involvement of MALAT1 in type I IFNs-mediated SLE by up-regulating OAS2, OAS3, and OASL.

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Section: Discussionmentioning

confidence: 99%

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Gao¹,

Tan²,

Luo³

2020

Braz J Med Biol Res

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“…Necrotic cell death is overall increased in SLE patients due to oxidative stress-induced mTOR-dependent expansion of CD3 + CD4 − CD8 − double-negative (DN) T cells [29,30]. These T cells also play critical roles in pathogenesis of SLE patients [31]. Importantly, DN T cells are expanded in the liver of lupus-prone mice [32,33].…”

Section: Discussionmentioning

confidence: 99%

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Liu

Oaks

et al. 2015

Clinical Immunology

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Liver disease (LD), defined as ≥2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 ± 0.7) relative to those without (5.8 ± 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 ± 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment.

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“…Healthy sex-and age-matched control cells were also used for experiments herein. Briefly, peripheral venous blood was collected in heparin-lithium tubes and PBMCs were prepared with Ficoll-Paque centrifugation, as previously described (84).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus

Wang

Mizui

Zeng

et al. 2016

Journal of Clinical Investigation

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Systemic lupus erythematosus (SLE) is a devastating multisystemic autoimmune disorder. However, the molecular mechanisms underlying its pathogenesis remain elusive. Some patients with Noonan syndrome, a congenital disorder predominantly caused by gain-of-function mutations in the protein tyrosine phosphatase SH2 domain-containing PTP (SHP2), have been shown to develop SLE, suggesting a functional correlation between phosphatase activity and systemic autoimmunity. To test this directly, we measured SHP2 activity in spleen lysates isolated from lupus-prone MRL/lpr mice and found it was markedly increased compared with that in control mice. Similar increases in SHP2 activity were seen in peripheral blood mononuclear cells isolated from lupus patients relative to healthy patients. To determine whether SHP2 alters autoimmunity and related immunopathology, we treated MRL/lpr mice with an SHP2 inhibitor and found increased life span, suppressed crescentic glomerulonephritis, reduced spleen size, and diminished skin lesions. SHP2 inhibition also reduced numbers of double-negative T cells, normalized ERK/MAPK signaling, and decreased production of IFN-γ and IL-17A/F, 2 cytokines involved in SLE-associated organ damage. Moreover, in cultured human lupus T cells, SHP2 inhibition reduced proliferation and decreased production of IFN-γ and IL-17A/F, further implicating SHP2 in lupus-associated immunopathology. Taken together, these data identify SHP2 as a critical regulator of SLE pathogenesis and suggest targeting of its activity as a potent treatment for lupus patients.

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A T cell gene expression panel for the diagnosis and monitoring of disease activity in patients with systemic lupus erythematosus

Cited by 31 publications

References 36 publications

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus

Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus

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