A Novel Monoclonal Antibody against Human CD80 and its Immune Protection in a Mouse Lupus-like Disease

Shi, Qin; Gao, Zhongcai; Xie, Fang; Wang, L F; Gu, Yuan; Yang, Tao; Huang, Li; Qian, Qihong; Qiu, Yu Hua

doi:10.1177/039463201102400304

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…Blockade of CD80 by monoclonal antibody has been shown in the pristane-induced lupus mouse model to attenuate both the inflammatory response and the severity of SLE hallmarks [55]. It has been further shown in a murine SLE model that following treatment with CTLA4-Ig (Abatacept), a recombinant fusion protein that contains the Fc fragment of human IgG1 and binds either to CD80 or CD86 with a much higher avidity than CD28, that there is a reduction in both numbers of autoreactive B cells and autoantibodies [56].…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of n-3, n-6 and n-9 Unsaturated Fatty Acid-Rich Diet Consumption on Lupus Nephritis, Autoantibody Production and CD4+ T Cell-Related Gene Responses in the Autoimmune NZBWF1 Mouse

et al. 2014

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Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical and clinical evidence that SLE patients may benefit from consumption of n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to compare the effects of dietary lipids on the onset and severity of autoimmune glomerulonephritis after consuming: 1) n-3 PUFA-rich diet containing docosahexaenoic acid-enriched fish oil (DFO), 2) n-6 PUFA-rich Western-type diet containing corn oil (CRN) or 3) n-9 monounsaturated fatty acid (MUFA)-rich Mediterranean-type diet containing high oleic safflower oil (HOS). Elevated plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A focused PCR array was used to relate these findings to the expression of 84 genes associated with CD4+ T cell function in the spleen and kidney both prior to and after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T cell-related genes in kidney and/or spleen at wk 34. These genes were associated with the inflammatory response, antigen presentation, T cell activation, B cell activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of representative affected genes confirmed that n-3 PUFA consumption was associated with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6 PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study are currently under consideration as biomarkers and/or biotherapeutic targets for SLE and other autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Comparative Effects of n-3, n-6 and n-9 Unsaturated Fatty Acid-Rich Diet Consumption on Lupus Nephritis, Autoantibody Production and CD4+ T Cell-Related Gene Responses in the Autoimmune NZBWF1 Mouse

et al. 2014

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“…In a pristane-induced lupus-like disease mouse model, monoclonal antibody against CD80 was shown to be able to attenuate inflammatory response and severity of lupus-like signs [46]. …”

Section: Costimulatory Molecules and Slementioning

confidence: 99%

Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

Kow

Mak

2013

Clinical and Developmental Immunology

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System lupus erythematosus (SLE) is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

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“…Expression of CD152 ligands also appears to be relevant in SLE. High CD80 expression on CD4 + T cells correlates with disease severity [ 30 ], and treatment with αCD80 Ab reduces disease severity in the pristine-induced murine model of disease [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint receptors in regulating immune reactivity in rheumatic disease

et al. 2014

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Immune checkpoint regulators are critical modulators of the immune system, allowing the initiation of a productive immune response and preventing the onset of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions such as the production of cytokines. In autoimmune rheumatic diseases, impaired tolerance leads to the development of diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome. Targeting the pathways of the inhibitory immune checkpoint molecules CD152 (cytotoxic T lymphocyte antigen-4) and CD279 (programmed death-1) in cancer shows robust anti-tumor responses and tumor regression. This observation suggests that, in autoimmune diseases, the converse strategy of engaging these molecules may alleviate inflammation owing to the success of abatacept (CD152-Ig) in rheumatoid arthritis patients. We review the preclinical and clinical developments in targeting immune checkpoint regulators in rheumatic disease.

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A Novel Monoclonal Antibody against Human CD80 and its Immune Protection in a Mouse Lupus-like Disease

Cited by 18 publications

References 38 publications

Comparative Effects of n-3, n-6 and n-9 Unsaturated Fatty Acid-Rich Diet Consumption on Lupus Nephritis, Autoantibody Production and CD4+ T Cell-Related Gene Responses in the Autoimmune NZBWF1 Mouse

Comparative Effects of n-3, n-6 and n-9 Unsaturated Fatty Acid-Rich Diet Consumption on Lupus Nephritis, Autoantibody Production and CD4+ T Cell-Related Gene Responses in the Autoimmune NZBWF1 Mouse

Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

Immune checkpoint receptors in regulating immune reactivity in rheumatic disease

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