title: Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes.
abstract: T lymphocytes from patients with Systemic Lupus Erythematosus (SLE) display multiple abnormalities, including increased cell activation, abnormal cell death by apoptosis and impairment of autophagy pathway. In the present study we report the presence of specific antibodies to D4GDI, a small GTPase family inhibitor, in a significant percentage (46%) of SLE patient sera. We also found a significant association between the presence of these autoantibodies and hematologic manifestations occurring in these patients. Investigating the possible implication of anti-D4GDI autoantibodies in SLE pathogenesis or progression, we found that these antibodies were capable of binding D4GDI expressed at the lymphocyte surface and triggering a series of subcellular events, including Rho GTPase activation. These antibodies were also able to induce autophagy in T cells from both healthy donors and SLE patients, but only those negative to these antibodies. We can conclude that anti-D4GDI autoantibodies could be capable of triggering important responses in T cells such as cytoskeleton remodeling and autophagy pathway and that, in SLE patients, the chronic exposure to these specific autoantibodies could lead to the selection of autophagy-resistant T cell clones contributing to the pathogenesis of the disease.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbati
authors.affiliation: Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Vomero
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Vona
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Colasanti
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vacirca
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Camerini
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Crescenzi
authors.affiliation: Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Pendolino
authors.affiliation: Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Truglia
authors.affiliation: Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Tina
authors.initials: T
authors.lastname: Garofalo
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.affiliation: Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" University, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy; San Raffaele Pisana Institute, Rome, Italy. Electronic address: malorni@iss.it.
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; San Raffaele Pisana Institute, Rome, Italy. Electronic address: elena.ortona@iss.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001343:Autophagy / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000276:immunology*
chemical_list: C569658:ARHGDIB protein, human; D001323:Autoantibodies; D034741:RNA, Small Interfering; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D020741:rho GTP-Binding Proteins
keywords: Autophagy; Cytoskeleton; D4GDI; Lipid rafts; Systemic lupus erythematosus