Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Abstract

Summary: Autism affects 1 in 110 new births, and it has no single etiology with uniform agreement. This has a significant impact on the quality of life for individuals who have been diagnosed with autism. Although autism has a spectrum quality with a shared diagnosis, it presents a uniquely different clinical appearance in each individual. Recent research of suspected immunological factors have provided more support for a probable immunological process or for processes that may play a role in the acquisition of an autistic condition. These factors include prenatal, genetic, and postnatal findings, as well as the discovery of a dysfunctional chronic pro-inflammatory state in brain tissue and cerebrospinal fluid in subsets of autistic patients. These findings offer new theories that may lead to the development of disease modification or preventative therapeutic options in the near future. This article reviews prenatal, genetic, and observed immune aspects of the autism condition that may be risk factors in the presentation of the autistic clinical phenotype. Historical immune interventions in autism are reviewed and potential new therapies and interventions are discussed.

Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy

“…The potential role of serotonergic transmission and NMDA receptors in the modulation of neuroinflammation has also been studied and could open new therapeutic perspectives to address the behavioral deficits in ASD [24,54]. Buspirone [95,[201][202][203], fluoxetine [204][205][206][207][208], escitalopram [209,210], citalopram [211], sertraline [212][213][214], D cycloserine [186,[215][216][217][218], amantadine [219], and memantine [220][221][222] have already been used in clinical research into autism.…”

“…In the year 2000, Sandler et al [191] described a series of autistic patients with regressive autistic traits and chronic diarrhea. Treatment with the antibiotic vancomycin was successful in providing short-term improvement in 8 of 10 children, but the gains did not endure [24].…”

Exploring the Potential Role of Inflammation as an Etiological Process in ASD

“…Among them, corticosteroids such as prednisone, an immunosuppressive glucocorticoid utilized for treatment of inflammatory and autoimmune conditions (Stigler et al 2009), have offered short-term improvement in language and social enhancement when taken in low doses (Chez and Guido-Estrada 2010;. A case study of a 3.5-year-old boy with autoimmune lymphoproliferative syndrome and comorbid ASD reported that after undergoing prednisone therapy for 1 month, the child showed an improvement in ASD symptoms characterized by better attention, language skills, awareness of environment, and purposeful directed behavior (Shenoy et al 2000).…”

Theoretical aspects of autism: Causes—A review

“…Maternal immune activation due to prenatal viral exposure can lead to an increase in maternal IL-6 levels and altered gene expression, which potentially could precipitate autistic behavior and neuropathology in the fetus later in time or after birth (Parker-Athill and Tan, 2010). A dysfunctional chronic pro-inflammatory state has been shown to exist in the brain and cerebral spinal fluid in subsets of autistic patients (Chez and Guido-Estrada, 2010). It is theorized that preexisting autoreactive T-lymphocytes may migrate across the blood-brain barrier and induce activation of local antigen-presenting cells, such as microglia and astrocytes.…”