title: An autistic endophenotype results in complex immune dysfunction in healthy siblings of autistic children.
abstract: BACKGROUND
  Endophenotypes are simple biological aspects of a disease that can be observed in unaffected relatives at a higher rate than in the general population; an "autism endophenotype" justifies the observation that a mild reduction in ideational fluency and nonverbal generativity might be observed in healthy, unaffected relatives of children with autism. Because it is becoming apparent that autism is associated with given alleles encoding within the human leukocyte antigens region, a region of pivotal importance in immunity, we examined whether the "autism endophenotype" would extend its effects on the immune system.
  
  
  METHODS
  Multiple immune parameters were analyzed in autistic children (AC) (n = 20), their siblings (HSAC) (n = 15), and age- and gender-comparable healthy control subjects (HC) (n = 20) without any familiarity for autism.
  
  
  RESULTS
  The immune profiles of HSAC were significantly more similar to those of their autistic siblings than to what was observed in HC. Thus, in AC and HSAC compared with HC: 1) proinflammatory and interleukin-10-producing immune cells were augmented (p < .01 in both comparisons); 2) CD8(+) naïve (CD45RA(+)/CCR7+) T lymphocytes were increased (p < .0001 and p = .001); and 3) CD8(+) effector memory (CD45RA(-)/CCR7-) (p < .0001 and p = .03) as well as CD4(+) terminally differentiated (CD45RA(-)/CCR7+) (p < .05 in both comparisons) lymphocytes were diminished. Serum autoantibodies (GM1) could be detected in 10% of AC children alone.
  
  
  CONCLUSIONS
  Results of this pilot study indicate that a complex immune dysfunction is present both in autistic children and in their non-autistic siblings and show the presence of an "autism endophenotype" that expands its effects on immunologic functions.
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation IRCCS-S.M. Nascente, Italy. msaresella@dongnocchi.it
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.forename: Franca Rosa
authors.initials: FR
authors.lastname: Guerini
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.forename: Lara
authors.initials: L
authors.lastname: Ceresa
authors.forename: Milena
authors.initials: M
authors.lastname: Zanzottera
authors.forename: Beatrice
authors.initials: B
authors.lastname: Rusconi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maggioni
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000293:Adolescent; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000378:metabolism*; D001321:Autistic Disorder / Q000150:complications* / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D054353:Perforin / Q000378:metabolism; D035781:Siblings; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines; D014764:Viral Proteins; D054353:Perforin; D053804:Granzymes