Identification of autoantibodies associated with systemic lupus erythematosus

Lim, Yeunhwan; Lee, Ho-Sung; Lee, Seongeun; Park, Sae-Young; Kim, Jongwan; Cho, Bomsoo; Lee, Hosoon; Kim, Hae‐Yeong; Lee, Eun-Bong; Song, Yeong Wook; Jeoung, Dooil

doi:10.1016/s0006-291x(02)00637-x

Cited by 56 publications

(51 citation statements)

References 33 publications

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“…We have previously shown that anti-Gal-8 autoantibodies produced by SLE patients block the interaction of Gal-8 with β1 integrins involved in its apoptotic action upon activated T cells (Norambuena et al, 2009). Autoantibodies against diff erent members of the galectin family such as Gal-1, -2, -3, and -4 been detected in patients with diff erent types of autoimmune diseases and in cancer (Lutomski et al, 1997;Giordanengo et al, 2001;Jensen-Jarolim et al, 2001;Lim et al, 2002;Romero et al, 2006;Montiel et al, 2010). However, whether autoantibodies against galectins interfere with galectin function in the immune system and whether they play pathogenic roles are poorly studied.…”

Section: Discussionmentioning

confidence: 99%

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

et al. 2013

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Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on diff erent cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its eff ects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this eff ect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these eff ects.

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Section: Discussionmentioning

confidence: 99%

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

et al. 2013

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“…72 In particular, autoantibodies to the catalytic fragment of PARP-1 were found in the sera of nearly 50% patients with SLE whereas they were not present in the sera of patients with rheumatoid arthritis, systemic sclerosis or healthy donors. 73,74 It is noted that in the standard 'supershift' experiment in Figure 4d, all three antibodies caused a neutralizing effect rather than a 'supershifting' one. This suggests that the antibodies likely interfered directly with the binding of PARP-1 to DNA by, for example, recognizing epitopes located within the region of the protein that interact with DNA.…”

Section: Parp-1 Regulates Il-10 Snp-mediated Transcription Ey Chung Ementioning

confidence: 92%

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by the dysregulation of T and B cells that leads to hyperactivity of B cells and production of autoantibodies, and involves both environmental and genetic factors. Interleukin-10 (IL-10) is a candidate susceptibility gene in SLE. In particular, three IL-10 promoter singlenucleotide polymorphisms (SNPs; À1082A/G, À819T/C and À592A/C) are strongly associated with the pathogenesis of SLE. We found that the homozygous GCC haplotype linked to greater SLE severity confers higher IL-10 gene transcriptional activity than the ATA haplotype in macrophages that encounter apoptotic cells, because of the differential DNA binding to the À592 SNP by a nuclear protein uniquely induced by apoptotic cells. We identified this protein as poly(ADP-ribose) polymerase-1, confirmed its physiological role and characterized its molecular properties in modulating IL-10 production during phagocytosis of apoptotic cells. This study unveils a novel direct link between DNA damage repair/apoptosis pathways and IL-10-mediated immune regulation.

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“…This analysis can also be applied to patients with autoimmune disease (20), such as Sjögren's syndrome (34), systemic lupus erythematosus (24), and giant cell arteritis and polymyalgia rheumatica (40).…”

Section: Discussionmentioning

confidence: 99%

Serological Identification of Endothelial Antigens Predominantly Recognized in Kawasaki Disease Patients by Recombinant Expression Cloning

Kaneko

Ono

Matsubara

et al. 2004

Microbiology and Immunology

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We showed IgG immune response against endothelial antigens in sera obtained from convalescent Kawasaki disease (KD) patients after recovery from the disease during the follow‐up period using serological analysis of recombinant cDNA expression library (SEREX) methodology. We identified 46 antigens represented by 69 clones by immunoscreening of a cDNA expression library from tumor necrosis factor‐α (TNFα) treated human umbilical vein endothelial cells (HUVEC) with sera from 4 KD patients. They included ubiquitin pathway proteins, transcriptional factors, signal transduction molecules, metabolic enzymes, cytoskeletal proteins, an adhesion molecule, and a cell cycle protein. By serological survey using phage plaque assay, sera from 5 non‐KD patients were rarely reactive with the antigens. Among the antigens, tropomyosin was most frequently isolated (18 of 69 clones). Seventeen of the 18 clones were identified using KD3 serum. The second most frequently isolated antigen was also a cytoskeletal protein, called T‐plastin (3 of 69 clones).

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Identification of autoantibodies associated with systemic lupus erythematosus

Cited by 56 publications

References 33 publications

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

Serological Identification of Endothelial Antigens Predominantly Recognized in Kawasaki Disease Patients by Recombinant Expression Cloning

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