A distinct pattern of mRNA expression by monocytes is found in a subset of children with autism spectrum disorders (ASD) who present with recurrent infection, repeated loss of cognitive skills, and persistent gastrointestinal (GI) symptoms. (51.16)

Abstract

Abstract A subset of ASD children (ASD Test Group) characterized by repeated loss of cognitive skills triggered by infection and frequent persistent GI symptoms were studied. We evaluated mRNA expression by peripheral blood (PB) monocytes in ASD test group (N=20, median 8 y) , ASD controls(N=22, median 7.6 y) , and normal control children (N=10, median 5.5 y) as well as the mothers of the ASD test (N=19) and ASD control (N=22) groups. We found that 568 genes were up-regulated and 72 genes were down-regulated (>2 fold) in the ASD test group versus 469 up-regulated and 57 down-regulated in the control groups. Only the ASD control group displayed up-regulation of CCL7 and CCL2 and down-regulation of IL-6 and CD86. The ASD test group mothers revealed up-regulation of 175 genes including CCL7 and down-regulation of 57 genes as compared to the ASD control mothers. The ASD test group also revealed decreased spontaneous production of IL-6 and IL-1β by PB mononuclear cells compared to controls. The 16/20 ASD test group children with persistent GI symptoms revealed up-regulation of CCL7 (>5 fold) and CCL2 and down-regulation of inflammatory mediators (IL-6, IL-23, IL-1α/IL-1β, CD86, and other chemokines) as compared to ASD and normal controls. Our results indicate a distinct pattern of mRNA expression in PB monocytes in the ASD subset with characteristic clinical features. Interestingly, CCL7 and CCL2 are up-regulated in the brain in various neurodegenerative disorders.