The immune response in autism: a new frontier for autism research
Paul Ashwood *, 1 , Sharifia Wills 
andJudy Van de Water
Full article at:
http://www.jleukbio.org/cgi/content/full/80/1/1
extract, translated from English
Autism spectrum disorders (BP) are among the pervasive developmental disorders that develop during childhood. They are characterized by disturbances in social interaction, verbal and nonverbal behaviors and the presence of stereotyped and repetitive. Currently, the etiology of TA is largely unknown, but it is thought that genetic factors, environmental, immune and neurological play a role in the development of TA. Recently, more and more researches have focused on the connection between the immune and nervous system, including its role possible in the development of TA. These neuroimmune interactions begin early during embryogenesis and persist throughout the life of the individual, a normal neurological development is dependent upon an appropriate immune response. Immune aberrations consistent with a dysregulation of the immune response, which were previously reported in autistic children included abnormal levels of T cell type 1 T H 1) / T H 2 cytokine profiles, the lower levels of lymphocyte, T cell mitogen response, and an abnormal level of serum immunoglobulin. Furthermore, the autistic was associated with autoimmunity and an association with genes such as leukocyte antigens (HLA)-DRB1 and complement C4 alleles described. It is possible that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of TA. This paper will review the status of research linking the immune response and autism.
CONCLUSIONS:
TAs are a very heterogeneous group of disorders with multiple phenotypes and subgroups that share common behavioral abnormalities. This inherent complexity has made it extremely difficult to understand the etiology of LD. Among the literature describing studies on the immunology of TA, there are many differences and unconfirmed reports. Many studies report apparently conflicting results, and to date, no consensus with respect to disorders of the immune system could not be found. However there are reports of increasing number of immune dysfunction in autism, there is a growing awareness that immune dysfunction may to play a role at least one (of the) subgroup (s) of autistic patients, if not all. In addition, various hypotheses have tried to link the activity of immune dysfunction and autism, such as abnormalities of the immune system of the mother in early pregnancy, an increased incidence of autoimmunity in families, childhood immunizations, and the generation of animal models based on immune parameters. A clear definition of the sub-groups of patients with LD using modern diagnostic tools may help to better define the results of these studies. The neurological and immune system are inextricably related to early embryo development. Abnormalities of the immune system before or during birth are capable of altering levels of cytokines, chemokines, neurotransmitters, neuropeptides, as well as hormone levels. Each of these substances influence the course of dévellopement nervous system and / or immune directly or through secondary actions. A development of the disturbances can be the beginning of a continuous cycle of damage and disruption of both systems. There are many pathways that can lead to the diagnosis of autism. For some it may begin with a genetic susceptibility, and for others infection or abnormalities of the immune system may play a key role. Further studies on the interactions of the nervous system, immune and endocrine systems may help unravel the mystery of autism. [...]
Original in English:
| ABSTRACT |
Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disorders, which occur in childhood. They are characterized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. Recently, increasing research has focused on the connections between the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual’s lifetime, with successful neurodevelopment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnormal or skewed T helper cell type 1 (T H 1)/T H 2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbalance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including human leukocyte antigen (HLA)-DRB1 and complement C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of ASD. This review will examine the status of the research linking the immune response with ASD.
Key Words: autism spectrum disorder (ASD) • neurodevelopment • neurokine • immunity • inflammation • cytokines
| CONCLUSION |
The ASD are an extremely heterogenous group of disorders with multiple phenotypes and subgroups that share behavioral commanalities. This inherent complexity has made deciphering the etiology of the broad spectrum of ASD extremely difficult. Within the literature describing immune-based studies in ASD, there are a number of discrepancies and unreplicated reports. Numerous studies report apparently conflicting results, and thus far, no consensus about the described immune findings has been reached. However, with increasing reports of immune dysfunction in autism, there is a growing awareness and concern that immune dysfunction may play a role in, if not all, at least a subgroup(s) of patients with autism. Moreover, various hypotheses have attempted to link dysfunctional immune activity and autism, such as maternal immune abnormalities during early pregnancy, increased incidence of familial autoimmunity, childhood vaccinations, and the generation of autism animal models based on immune parameters. A clear-cut definition of the groups or subgroups of ASD patients using modern diagnostic tools may help to better define these study results. The neurological and immune systems are inextricably intertwined beginning in the embryonic stage of life. Pre- or perinatal immune dysregularities are capable of altering levels of cytokines, chemokines, neurotransmitters, neuropeptides, as well as hormones. Each of these substances may influence the course of development in the nervous and/or immune systems primarily or through secondary action. A development perturbation may be the beginning of a continual cycle of damage or disruption to both systems. There are numerous pathways that may lead to the diagnosis of ASD. In some, it may begin with genetic susceptibility, and in others, infection or immune abnormalities may play a key role. Further study of the reciprocal actions of the nervous, immune, and endocrine systems may help to unravel the mystery of ASD. Moreover, while the extent to which many of the observations discussed herein are involved in the pathogenesis of autism is unknown, it cannot be discounted that immune dysfunction is an epiphenomenon or a consequence of the disease. Comprehensive studies of autism and age-matched control individuals and their families are necessary for more conclusive results.
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