Biologic therapies in systemic lupus erythematosus

2016 ◽  
Author(s):  
Maria Mouyis ◽  
David Isenberg
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Treatment Options ◽  
Biologic Therapies ◽  
Systemic Lupus ◽  
New Treatment ◽  
Anti Cd20

This chapter looks at the various biologic or target therapies that have been trialled and tested in the last two decades. The treatment of systemic lupus erythematosus (SLE) has progressed over the last few years due to an increased understanding of its pathogenesis; beginning with rituximab, one of the first biologics to be used, the chapter covers therapies up to the present day. Each subsection highlights the relevant mechanism of action which has led to new treatment options: anti-CD20 and 22, anti-B cell activating factors, anti-interferon alpha and anti-T cell activation. A summarized table is available providing a concise summary of the latest biologic therapies in treating SLE. The role of biologic therapies as monotherapy is still being defined, and with time there will be further change in the treatments available and the approach to the treatment of SLE using biologic therapies.

scholarly journals Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

2015 ◽  
Vol 182 (1) ◽  
pp. 1-13 ◽  
Author(s):  
J. P. Mackern-Oberti ◽  
J. Obreque ◽  
G. P. Méndez ◽  
C. Llanos ◽  
A. M. Kalergis
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Carbon Monoxide ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus ◽  
Target Organs

Abstract MP41: A Role Of Isolevuglandins In Systemic Lupus Erythematosus Associated Autoimmunity And Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
David M Patrick ◽  
Nestor de la Visitacion ◽  
Michelle J Ormseth ◽  
Charles Stein ◽  
Sean S Davies ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Immune Cell ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Immune Cell Activation ◽  
Systemic Immune Activation

Essential hypertension and systemic lupus erythematosus (SLE) are devastating conditions that disproportionately affect women. SLE has heterogeneous manifestations and treatment is limited to the use of non-specific global immunosuppression. Importantly, there is an increased prevalence of hypertension in women with SLE compared to healthy controls. Isolevuglandins (IsoLGs) are oxidation products of fatty acids that form as a result of reactive oxygen species. These molecules adduct covalently to lysine residues of proteins. Adducted proteins are then presented as autoantigens to T-cells resulting in immune cell activation. Previous studies have shown an essential role of IsoLGs in immune cell activation and the development of hypertension in animal models. We hypothesize that isoLGs are important for the development of hypertension and systemic immune activation in SLE. We first examined isoLG adduct accumulation within monocytes of human subjects with SLE compared to healthy controls. By flow cytometry, we found marked accumulation of isoLG adducts within CD14 + monocytes (34.2% ± 12.4% vs 3.81% ± 2.1% of CD14 + , N = 10-11, P <0.05). We confirmed this increase in isoLG adducts by mass spectrometry. To determine a causative role of isoLG adducts in immune activation and hypertension in SLE, we employed the B6.SLE123 and NZBWF1 mouse models of SLE. Animals were treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA) or vehicle beginning at 7 weeks and were sacrificed at 32 weeks of age. C57BL/6 and NZW were used as controls. Importantly, treatment with 2-HOBA attenuated blood pressure in both mouse models (systolic BP 136.2 ± 5.6 mmHg for B6.SLE123 vs 120.9 ± 4.46 mmHg for B6.SLE123 +2HOBA; 164.7 ± 24.4 mmHg for NZBWF1 vs 136.9 ± 14.9 mmHg for NZBWF1 +2HOBA, N = 6-8, P < 0.05). Moreover, treatment with 2-HOBA reduced albuminuria and renal injury in the B6.SLE123 model (albumin/creatinine ratio 33.8 ± 2.0 x 10 -2 μg/mg for B6.SLE123 vs 5.5 ± 0.9 x 10 -2 μg/mg for B6.SLE123 +2HOBA, N = 7-9, P < 0.05). Finally, immune cell accumulation in primary and secondary lymphoid organs is significantly attenuated by 2-HOBA. These studies suggest a critical role of isoLG adduct accumulation in both systemic immune activation and hypertension in SLE.

scholarly journals MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1433 ◽  
Author(s):  
Chuang ◽  
Tan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Therapeutic Targets ◽  
T Cell Signaling ◽  
Systemic Lupus

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE.

scholarly journals Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Marco Tucci ◽  
Stefania Stucci ◽  
Sabino Strippoli ◽  
Francesco Silvestris
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
B Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Cells ◽  
Systemic Lupus ◽  
Regulatory Functions

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

Impaired T-cell activation in patients with systemic lupus erythematosus

1989 ◽  
Vol 9 (6) ◽  
pp. 469-476 ◽  
Author(s):  
Stanislaw Sierakowski ◽  
Eugene J. Kucharz ◽  
Robert W. Lightfoot ◽  
James S. Goodwin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus

scholarly journals Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus

2012 ◽  
Vol 64 (9) ◽  
pp. 2953-2963 ◽  
Author(s):  
Shu Ding ◽  
Yunsheng Liang ◽  
Ming Zhao ◽  
Gongping Liang ◽  
Hai Long ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Systemic Lupus

scholarly journals Defective CD2 pathway T cell activation in systemic lupus erythematosus

1991 ◽  
Vol 34 (5) ◽  
pp. 561-571 ◽  
Author(s):  
David A. Fox ◽  
Jo Ann Millard ◽  
Jonathan Treisman ◽  
Wendy Zeldes ◽  
Alice Bergman ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Systemic Lupus

scholarly journals Glucose Oxidation Is Critical for CD4+ T Cell Activation in a Mouse Model of Systemic Lupus Erythematosus

2015 ◽  
Vol 196 (1) ◽  
pp. 80-90 ◽  
Author(s):  
Yiming Yin ◽  
Seung-Chul Choi ◽  
Zhiwei Xu ◽  
Leilani Zeumer ◽  
Nathalie Kanda ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Mouse Model ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Glucose Oxidation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Systemic Lupus
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