TY - JOUR
T1 - An Autistic Endophenotype Results in Complex Immune Dysfunction in Healthy Siblings of Autistic Children
AU - Saresella, Marina
AU - Marventano, Ivana
AU - Guerini, Franca Rosa
AU - Mancuso, Roberta
AU - Ceresa, Lara
AU - Zanzottera, Milena
AU - Rusconi, Beatrice
AU - Maggioni, Emanuela
AU - Tinelli, Carmine
AU - Clerici, Mario
PY - 2009/11/15
Y1 - 2009/11/15
N2 - 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.
AB - 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.
KW - Autism
KW - autistic endophenotype
KW - cytokines
KW - immunology
KW - T lymphocytes
KW - thymus
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U2 - 10.1016/j.biopsych.2009.06.020
DO - 10.1016/j.biopsych.2009.06.020
M3 - Article
C2 - 19699471
AN - SCOPUS:70350575737
VL - 66
SP - 978
EP - 984
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 10
ER -