Characterization of Immune Cell Phenotypes in Adults with Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in verbal and non-verbal communication, impaired social interactions and repetitive behaviors. There is evidence of a link between ASD symptoms and immune dysfunction, but few studies have been performed in adult patients to confirm this. In this work, we used flow cytometry to study immunological differences in peripheral blood mononuclear cells from 59 adult patients and 26 healthy control subjects to identify possible immune cell profiles related with this group of disorders. We analyzed six immune cell subpopulations (ie, B-cells, CD4(+) and CD8(+) T-cells, NK, NKT cells, and monocytes) and their corresponding stages of apoptosis and activation. The most noteworthy results showed that, compared to healthy controls, patients had increased percentages of CD8(+) T-cells and B-cells, and a decrease in the percentage of NKT cells. Regarding CD25 expression, we found overall CD25(+) overexpression, primarily in NK and NKT cells. Apoptosis percentage showed an increasing trend only in monocytes of patients. These data support a link between ASD and immune dysfunction, suggesting that specific cellular phenotypes and/or activation status of immune cells may be relevant in adult ASD.

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

“…Other important immune cell subsets show abnormalities in ASD. By means of flow cytometry, CD8(+) B and T lymphocyte numbers were increased in 59 adult ASD subjects compared to 26 control adults [ 87 ]. Alterations in activation profiles for T cells and in adaptive cellular immune functions have been demonstrated in 66 children (2–5 years old) with ASD compared to 73 age-matched typically developing controls [ 88 ].…”

Immune Abnormalities in Autism Spectrum Disorder—Could They Hold Promise for Causative Treatment?

“…Serum levels of macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) were elevated and significantly correlated with intensification of autistic behaviors [ 89 ]. A higher percentage of CD8 + T cells (21.68% vs. 16.48%) and B cells (8.17% vs. 6.97%) and a decrease of CD4 + /CD8 + ratio (3.01 vs. 3.97) was reported in 59 adult patients with ASD with a mean age of about 24 years versus a control group composed of 26 individuals, two of which were first-degree relatives, with no significant differences regarding age and gender of study participants [ 90 ].…”

“…However, serum concentrations of those interleukins and subpopulations of CD56 Dim and CD56 Bright were not assessed. In 59 adult ASD patients, significantly lower numbers of NKT cells, with normal numbers of NK cells, and increased numbers of stimulated NKT and NK cells expressing CD25 + were described [ 90 ].…”

“…The difference was small (0.588 × 10 3 cells/mm 3 vs. 0.491 × 10 3 cells/mm 3 ), but statistically significant. Monocytes in children with ASD were also found to be positive for a surface receptor that is thought to be expressed on cells susceptible to apoptosis [ 90 ]. Enstrom et al [ 155 ], in a small study on 17 ASD children and 16 healthy controls, stimulated monocytes with Toll-like receptor (TLR) ligands and observed differences between cytokine profiles in autistic and healthy children.…”

Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events?

“…Interestingly, this increase in NK cells is associated with a deficient response following in vitro stimulation [16], despite the presence of an activating killer-cell immunoglobulin-like receptor (KIR)/HLA complex that could promote immune activation in ASD. Nevertheless, the scarcity of NK-cell studies in adult patients [25] prompted us to evaluate their characteristics in a cohort of adults with hf-ASD.…”