Download the involvement of innate immunity in development of autism

THE INVOLVEMENT OF INNATE IMMUNITY IN DEVELOPMENT
OF AUTISM SPECTRUM DISORDERS
K. Yenkoyan1, T. Davtyan2, K. Fereshetyan1, A. Harutyunayn1
1
Yerevan State Medical University, Department of Biochemistry, Yerevan, Armenia
2
Armenicum Center, Department of Immunology, Yerevan, Armenia
Background
Nowadays there is a vital need of well-done scientific complex experiments coupled with clinics, which will clarify the etiolopathogenesis of autism spectrum disorders (ASD) and may ultimately
lead to new strategies for the prevention or cure ASDs.
The role of immune system in these processes seems to be crucial. It is very important to understand whether adaptive or innate immunity is involved in development of autism. In these first-step
studies we planned to find out the involvement of innate immune system in pathogenesis of autism.
Aim of the study
For this purpose different components of innate (quantity of natural killers, IL10-and TNF-α-produced monocytes, IL10-and TNF-α-produced CD14 cells, activity and intensity of respiratory
burst of monocytes/neutrophils) immune responses analyzed in the blood of autistic children.
Methods used
Children, 4-10 years of age, were divided into two groups: the control group consisted of absolutely healthy children (healthy control, n=12); the second group – children, who have a diagnosis
of autistic disorder and had not previously received any type of treatment (autistic, n=12). Protocol is approved by the Ethics Committee of Yerevan State Medical University after M. Heratsi.
All children meet the DSM-IV criteria for Autistic Disorder and this diagnosis is also corroborated by psychologists using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism
Diagnostic Observation Schedule (ADOS). Children with PDD-NOS, Asperger syndrome, seizure disorder, current ear infection, uncontrolled asthma, inability to equalize ear pressure, fragile
X syndrome and ongoing treatment with chelation medication were excluded from participation in this study. Quantitative analysis natural killers (CD3/CD16+56), production of Il-10 and
TNF-α by lymphocytes, monocytes, CD14 cells as well as activity and intensity of spontaneous and induced respiratory burst of monocytes/neutrophils was done using flow cytometry.
Respiratory burst of monocytes/neutrophils will be induced by chemotactic peptide N-formyl-Met-Leu-Phe (PMNL).
Summary of results
In autistic group the number on NK cells increased compared with minimal values of control reference range, and decreased in comparison with maximal values of control reference range. At
the same time percentage of NK (CD56+) cells was decreased in comparison with maximum values. The intensity of spontaneous and induced respiratory burst of monocytes and neutrophils
was in reference ranges values, but the percentages of involved monocytes and neutrophils in spontaneous and PMNL induced phagocytosis was dramatically increased. The potency of
monocytes and CD14+ cells to synthesize cytokines both anti-inflammatory Il10, as well as proinflammatory TNF-α was decreased in one group of autistic children and increased in the
other (p<0.05). The synthesis of Il10 was up regulated more than TNF-α and there were practically no changes between the decrease of TNF-α and Il10. These changes in producing the
anti-inflammatory Il10 and proinflammatory TNF-α were contra versa to the same changes in production of mentioned cytokines by lymphocytes showed by our previous studies.
Conclusion
Summarizing the study, we conclude that the innate immunity involved in development of autism mostly on the level of mediators.
We think that in autistic children, generally, the immune stress is obviously comes out and do not stress on the type of response. Prevalence of the immune (adaptive/innate) or inflammatory
response could change from stage to stage of disease development and the role of specific cytokines has to be determined. Hypothetically activation of Th1 or productions of specific
cytokine like TNF-α may destroy the structural integrity of hematoencephalic barrier. Interesting findings were observed in the potency of both adaptive and innate immunity cells to produce
cytokines: one group of autistic children responded in depressed manner, the other – in expressed manner. But these thoughts as well as their consequences have to be proofed by our further
studies.
RESULTS
CD56+ (NK-cells)
Percentage of Natural killers (CD56+),
B-cells (CD19+/CD3-), Total T-cells(CD3+),
T-helpers (CD3+/CD4+), T-cytotoxic cells (CD3+/CD8+)
(Natural
Quantitative analyses of IL-10 and TNF-alfa
produced CD14+ cells and monocytes
(total T cells %) (T
(B
cytotoxic cells
Intensity of spontaneous and induced respiratory burst of
monocytes/neutrophils
Activity of spontaneous and induced respiratory burst of
monocytes/neutrophils
(%)
(T-cytotoxic cells)
(%)
(%)
(%)