title: Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia.
abstract: A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin-mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia (ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin (IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease.
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Boggio
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
authors.forename: Casimiro L
authors.initials: CL
authors.lastname: Gigliotti
authors.affiliation: Division of Haematology, Department of Translational Medicine, UPO, Novara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Haematology Section, DISM, Azienda Sanitaria Universitaria Integrata S. M. Misericordia, Udine, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Toffoletti
authors.affiliation: Laboratory of Autoimmunity, Division for Experimental Pathophysiology and Immunology, Biocentre, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cappellano
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Clemente
authors.affiliation: Haematology Section, DISM, Azienda Sanitaria Universitaria Integrata S. M. Misericordia, Udine, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Puglisi
authors.affiliation: Division of Haematology, Department of Translational Medicine, UPO, Novara, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.affiliation: Division of Haematology, Department of Translational Medicine, UPO, Novara, Italy.
authors.forename: Michaela
authors.initials: M
authors.lastname: Cerri
authors.affiliation: Department of Haematology and Clinical Oncology "L. and A. Seragnoli", S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Vianelli
authors.affiliation: Haematology Section, Ospedale Niguarda CàGranda, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantoni
authors.affiliation: Haematology Section, Azienda Ospedaliera Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Tieghi
authors.affiliation: Haematology Section 1, Ospedale San Giovanni Battista Molinette, Torino, Italy.
authors.forename: Eloise
authors.initials: E
authors.lastname: Beggiato
authors.affiliation: Division of Haematology, Department of Translational Medicine, UPO, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Translational Medicine, UPO, Novara, Italy.
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.affiliation: Haematology Section, DISM, Azienda Sanitaria Universitaria Integrata S. M. Misericordia, Udine, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Diseases (IRCAD) and Department of Health Sciences, University of Piemonte Orientale (UPO), Novara, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
authors.affiliation: Haematology Section, DISM, Azienda Sanitaria Universitaria Integrata S. M. Misericordia, Udine, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D022423:Myeloid Cells / Q000473:pathology; D054353:Perforin / Q000235:genetics*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology
chemical_list: D020381:Interleukin-17; D019014:fas Receptor; D054353:Perforin; D016753:Interleukin-10
keywords: Fas function; PRF1 variations; Treg; cytokine secretion; immune thrombocytopenia