Associations between Monocyte and T Cell Cytokine Profiles in Autism Spectrum Disorders: Effects of Dysregulated Innate Immune Responses on Adaptive Responses to Recall Antigens in a Subset of ASD Children

Abstract

Changes in monocyte cytokine production with toll like receptor (TLR) agonists in subjects with autism spectrum disorders (ASD) were best reflected by the IL-1β/IL-10 ratios in our previous research. The IL-1β/IL-10 based subgrouping (low, normal, and high) of ASD samples revealed marked differences in microRNA expression, and mitochondrial respiration. However, it is unknown whether the IL-1β/IL-10 ratio based subgrouping is associated with changes in T cell cytokine profiles or monocyte cytokine profiles with non-TLR agonists. In ASD (n = 152) and non-ASD (n = 41) subjects, cytokine production by peripheral blood monocytes (PBMo) with TLR agonists and β-glucan, an inflammasome agonist, and T cell cytokine production by peripheral blood mononuclear cells (PBMCs) with recall antigens (Ags) (food and candida Ags) were concurrently measured. Changes in monocyte cytokine profiles were observed with β-glucan in the IL-1β/IL-10 ratio based ASD subgroups, along with changes in T cell cytokine production and ASD subgroup-specific correlations between T cell and monocyte cytokine production. Non-ASD controls revealed considerably less of such correlations. Altered innate immune responses in a subset of ASD children are not restricted to TLR pathways and correlated with changes in T cell cytokine production. Altered trained immunity may play a role in the above described changes.

Associations between Monocyte Cytokine Profiles and Co-Morbid Conditions in Autism Spectrum Disorders

“…Therefore, we decided to assess changes of monocyte cytokine parameters in association with co-morbid conditions frequently found in ASD subjects. We found GI symptoms along with NFA or FPIES like conditions in ASD subjects at high frequency (>60%), which was consistent to our previous studies [10,12,29]. Most of the ASD patients with GI symptoms had a history of FPIES like symptoms ( Table 2).…”

“…IIM is closely associated with changes in monocyte cytokine profiles [16]. Previously, we have found significant changes in monocyte cytokine profiles in a subset of ASD patients [10,11]. Therefore, this study addressed whether the specific monocyte cytokine parameters are associated with ASD co-morbid conditions.…”

“…In our previous studies, we focused on abnormalities of innate immunity, which plays a major role in the neuro-immune network including stress responses [10][11][12]. One of the reasons that we focused on innate immune abnormalities is based on findings from one of the most thoroughly studied animal models of ASD, maternal immune activation (MIA).…”

Resolution of EEG findings and clinical improvement in a patient with encephalopathy and ESES with a combination of immunomodulating agents other than corticosteroids: A case report

“…ELISA reagents were obtained from BD Biosciences (San Diego, CA, USA) and R & D (Minneapolis, MN, USA). PBMo were incubated overnight with and without stimuli of innate immunity [lipopolysaccharide (LPS) (0.1 μg/ml, GIBCO-BRL, Gaithersburg, MD, USA), zymosan (50 μg/ml, Sigma-Aldrich, St. Luis, Mo, USA), CL097 (20 μM, Invivogen, San Diego, CA, USA), and candida heat extract (HCKA, 10 7 cells/ml, Invivogen, as a source of ß-glucan) in the same culture conditions detailed previously [ 15 ].…”

TNF-α expression ratio of M1/M2 macrophages is a potential adjunctive tool for the diagnosis of autism spectrum disorder

“…In the periphery, increased expression of pro-in ammatory cytokines, including interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), transforming growth factor beta, IL-8, and IL-17 has been observed in the plasma, serum, and peripheral blood mononuclear cells (PBMCs) of patients with ASD (7,8). Antioxidant networks (e.g., superoxidase dismutase expression and activity) and the responses to innate immunity stimuli (e.g., lipopolysaccharide and zymosan) have been found to be dysregulated in the monocytes of ASD patients (9)(10)(11). In the central nervous system (CNS), a positron emission tomography study and a few postmortem studies have shown microglial activation in the brains of ASD patients (12)(13)(14)(15).…”