ABSTRACT
To verify correlations between HLA and autism spectrum disorders (ASD) we studied 61 Italian families with an ASD child; results showed such correlation in 65% of cases. Case-control and TDT analysis of intrafamilial transmission of SNPs, Msats, and HLA markers surrounding the α and ß blocks, indicated significant positive associations for MOGc*131 and D6S2239*105 alleles in ASD, and a negative association of MIB *332 allele in healthy siblings. Polymorphism haplotype analysis demonstrated that two haplotypes comprising the TNF-238(G)-TNF-308(G)-MIB*332-HLA-B*38-HLA-Cw*12 and the D6S265*218-HLA-A*23-MOGc*131-rs2857766(G) alleles are more frequently transmitted to ASD. MOGc and MIB loci are linked with ASD in Italian patients.
Subject(s)
Child Development Disorders, Pervasive/genetics , Genetic Linkage , Genetic Predisposition to Disease/genetics , HLA Antigens/genetics , Polymorphism, Single Nucleotide , Child , Female , Haplotypes , Humans , Italy , Male , Microsatellite Repeats/geneticsABSTRACT
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.