The effect of cell death in the initiation of lupus nephritis

Fenton, Kristin Andreassen

doi:10.1111/cei.12417

Cited by 47 publications

(39 citation statements)

References 64 publications

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“…54 During the early phases of lupus nephritis, autoimmune T cells respond to tissue injuries reacting against chromatin or nucleosomes derived from cell death, including apoptosis, necrosis, necroptosis, autophagy and possible disturbances in the clearance of dying cells, leading to differentiation of autoimmune lymphocytes. 55,56 Interestingly, SLE patients affected with lupus nephritis were seen to display higher serum levels of anti-gal-3 antibodies compared with controls; additionally, gal-3 stained in glomeruli in the majority of patients, while it was absent in controls. 38 Notably, gal-3 was expressed in distal tubules of normal kidneys.…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Galectin-3 in autoimmunity and autoimmune diseases

Oliveira

Gatto

Bassi

et al. 2015

Exp Biol Med (Maywood)

143

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Galectin-3 (gal-3) is a b-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/ non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra-or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases.

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Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Galectin-3 in autoimmunity and autoimmune diseases

Oliveira

Gatto

Bassi

et al. 2015

Exp Biol Med (Maywood)

143

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“…The enriched antibody responses to apoptotic proteins and IL-6 (a prominent drug target in SLE drug development) may indicate that dysregulated processes of cellular damage in GLMN can generate additional sources of antigens. 39 Our study has several limitations as the sample size is relatively small, no autoimmune disease controls were included and differences in ethnicity were not considered. In future studies we plan to examine if autoantibody reactivity patterns in SLE patients remain stable over time or tend to fluctuate, such as anti-dsDNA titers.…”

Section: Discussionmentioning

confidence: 99%

Multiparametric detection of autoantibodies in systemic lupus erythematosus

Budde

Zucht

Vordenbäumen

et al. 2016

Lupus

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Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease manifestations, disease progression and treatment response. Therefore, strategies to identify biomarkers that help distinguishing SLE subgroups are a major focus of biomarker research. We reasoned that a multiparametric autoantibody profiling approach combined with data mining tools could be applied to identify SLE patient clusters. We used a bead-based array containing 86 antigens including diverse nuclear and immune defense pathway proteins. Sixty-four autoantibodies were significantly (p < 0.05) increased in SLE (n ¼ 69) compared to healthy controls (HC, n ¼ 59). Using binary cut-off thresholds (95% quantile of HC), hierarchical clustering of SLE patients yields five clusters, which differ qualitatively and in their total number of autoantibodies. In two patient clusters the overall accumulated autoantibody reactivity of all antigens tested was 31% and 48%, respectively. We observed a positive association between the autoantibody signature present in these two patient clusters and the clinical manifestation of glomerulonephritis (GLMN). In addition, groups of autoantibodies directed against distinct intracellular compartments and/or biological motifs characterize the different SLE subgroups. Our findings highlight the relevant potential of multiparametric autoantibody detection and may contribute to a deeper understanding of the clinical and serological diversity of SLE. Lupus (2016) 25, 812-822.

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“…On the contrary, plasma C1q concentrations tend to be lower in high SLE activity and in lupus nephritis, also directly correlating with CIC-linked DNA levels [80]. These changes taken one with another can be accounted for reallocation of plasma DNA pool to CIC in the presence of high-avidity anti-dsDNA.…”

Section: Dna Elimination Pathway In Slementioning

confidence: 98%

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

Trofimenko¹

2017

Lupus

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The distinctive feature of systemic lupus erythematosus (SLE) is an immune reaction directed to diverse spectrum of autoantigens, which tends to change along with the disease spreading. The most common targets of the autoantibodies are protein and nucleoprotein components of cell nuclei: dsDNA, histones, nucleosomes, Sm antigen, and Ro and La antigens. Considering that the exact causes of this tolerance loss are unknown, a certain number of hypotheses are now discussed. One of the most promising is "waste disposal" concept, which makes a link between broken elimination of cellular debris, mononuclear phagocyte system dysfunction, and initiation of autoimmunity by the antigen presenting cells in SLE. This chapter concerns the ways nuclear antigens release from cells, necrosis, and apoptosis, as well as the key molecular mechanisms of transport and elimination of these antigens, its disturbances in SLE, and connection with innate immunity by mononuclear cells. Special atention is paid to nucleosomes and DNA degradation process, its principal factors (DNase I, C1q, SAP), blood DNA transportation by immune complexes, and immune stimulating action of DNA in SLE. Current pros and cons for the waste disposal concept and existing research trends in this ield are discussed.

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The effect of cell death in the initiation of lupus nephritis

Cited by 47 publications

References 64 publications

Galectin-3 in autoimmunity and autoimmune diseases

Galectin-3 in autoimmunity and autoimmune diseases

Multiparametric detection of autoantibodies in systemic lupus erythematosus

Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

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