title: Defective T cell fas function in patients with multiple sclerosis.
abstract: BACKGROUND
  Fas (CD95) triggers programmed cell death and is involved in shutting off the immune response. Inherited deleterious mutations hitting Fas or its signaling pathway cause autoimmune/lymphoproliferative syndrome (ALPS).
  
  
  OBJECTIVE
  To assess the possibility that decreased Fas function plays a role in development of MS.
  
  
  METHODS
  The authors evaluated Fas function in long-term T cell lines (21 days of culture) from 32 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 15 with primary progressive MS (PPMS) by assessing cell survival upon Fas triggering by monoclonal antibodies (Mab).
  
  
  RESULTS
  Fas-induced cell death was significantly lower in all patient groups than in controls, and lower in SPMS than in RRMS. Moreover, 8/15 patients with PPMS, 10/15 with SPMS, and 8/32 with RRMS were frankly resistant to Fas. Frequency of resistance to Fas-induced cell death was significantly higher in all patient groups than in controls (2/75), and higher in SPMS than in RRMS. The findings that the parents of two Fas-resistant patients were Fas-resistant and that fusion of T cells from two Fas-resistant patients with Fas-sensitive HUT78 cells gave rise to Fas-resistant hybrid lines suggest that Fas-resistance is due to inherited alterations of the Fas signaling pathway, with production of molecules exerting a dominant negative effect on a normal Fas system.
  
  
  CONCLUSIONS
  Defects of the immune response shutting-off system may be involved in the pathogenesis of MS, particularly in its progressive evolution.
authors.affiliation: Neurological Clinic, Department of Medical Science, University of Eastern Piedmont, Novara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Leone
authors.forename: S
authors.initials: S
authors.lastname: Bonissoni
authors.forename: S
authors.initials: S
authors.lastname: DeFranco
authors.forename: F
authors.initials: F
authors.lastname: Bottarel
authors.forename: C
authors.initials: C
authors.lastname: Mezzatesta
authors.forename: A
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: F
authors.initials: F
authors.lastname: Perla
authors.forename: F
authors.initials: F
authors.lastname: Monaco
authors.forename: U
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology* / Q000502:physiology*
chemical_list: D019014:fas Receptor