A volcanic explosion of autoantibodies in systemic lupus erythematosus: A diversity of 180 different antibodies found in SLE patients

Gal, Yaniv; Twig, Gilad; Shor, Dana Ben-Ami; Furer, Ariel; Sherer, Yaniv; Mozes, Oshry; Komisar, Orna; Slonimsky, Einat; Klang, Eyal; Lotan, Eyal; Welt, Mike; Marai, Ibrahim; Shina, Avi; Amital, Howard; Shoenfeld, Yehuda

doi:10.1016/j.autrev.2014.10.003

Cited by 296 publications

(228 citation statements)

References 42 publications

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“…Antibodies against C3 have been described in patients with autoimmune diseases, such as SLE (11)(12)(13)(14) or Crohn disease (15), in some nephrotic kidney diseases (16,17), and in dense deposit disease (DDD) (7) as well as in autoimmune-prone mice (12). Based on the limited functional studies of these antibodies, it is difficult to conclude whether they are a disease-relevant factor or a simple epiphenomenon, one among many, arising from the dysregulated immune response in the autoimmune diseases (18,19). To date, anti-C3 antibodies have been shown to inhibit the inactivation of C3b to iC3b by Factor I (FI) in the presence of complement receptor 1 (CR1) as a cofactor (14) and to prevent the clearance of apoptotic cells by mouse but not human macrophages (12).…”

Section: Lupus Nephritis (Ln)mentioning

confidence: 99%

Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis

Vasilev

Noé

Dragon-Durey

et al. 2015

Journal of Biological Chemistry

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Background: Autoantibodies against complement C3 are found in patients with the autoimmune disease systemic lupus erythematosus. Results: C3 autoantibodies are found in 30% of lupus nephritis patients and inhibit C3 interaction with the regulatory proteins Factor H and CR1. Conclusion: C3 autoantibodies have overt capability to overactivate complement. Significance: C3 autoantibodies can contribute to the pathological process in lupus nephritis.

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Section: Lupus Nephritis (Ln)mentioning

confidence: 99%

Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis

Vasilev

Noé

Dragon-Durey

et al. 2015

Journal of Biological Chemistry

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“…2,3,[13][14][15][16] From our antigen array, to our best knowledge, 50 autoantibody targets have been previously associated with SLE or other systemic autoimmune diseases. A further 36 novel autoantibody targets were identified in large-scale autoantibody screening studies at our labs using human cDNA libraries 9 to generate over 7000 human proteins and will be described in detail elsewhere (manuscript in preparation).…”

Section: Luminex Autoantibody Array Designmentioning

confidence: 99%

“…4 Indeed, a great number of antinuclear autoantibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCAs) found in SLE patients are directed against NET components and components of apoptotic blebs. 5 Over the past decades more than 180 different autoantibody specificities have been reported in SLE, 3 which greatly differ in their diagnostic sensitivity and specificity, association with clinical manifestations, disease activity and ethnicity. 2 Current diagnostic methods for determining autoantibodies in SLE have mainly focused on a relatively small set of autoantibody targets of which anti-dsDNA, anti-phospholipid and anti-Sm are important criteria for the clinical diagnosis and classification of SLE.…”

Section: Introductionmentioning

confidence: 99%

“…anti-U1-snRNP autoantibodies), cytoplasmic and extracellular, as well as miscellaneous proteins (summarized in Table 2). 2,3 It is presumed that an increased rate of apoptosis and the formation of neutrophil extracellular traps (NETs) generates neoantigens on proteins, which may be recognized as autoantigens in SLE. 4 Indeed, a great number of antinuclear autoantibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCAs) found in SLE patients are directed against NET components and components of apoptotic blebs.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Understanding the specificities of the antibodies is useful in clinical practice to further classify patients with lupus and help predict their disease course. [15,16] …”

Section: What Causes Lupus?mentioning

confidence: 99%