A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation

Autism Res. 2018 Mar;11(3):421-433. doi: 10.1002/aur.1906. Epub 2018 Feb 10.


Research has shown that a subset of the autism spectrum disorder (ASD) population presents with immune dysregulation. To explore this topic further, we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. In this study, participants were recruited based on a diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified. Participants also showed evidence of immune dysfunction based on abnormal levels of specific biomarkers, including CD40 ligand (CD154), lymphocyte stimulation, and T or B cell dysfunction. Of 17 screened patients, 14 completed the trial and received IVIG treatment (1 g/kg dose) for ten 21-day treatment cycles. The primary endpoint was disease improvement assessed using standardized cognitive and behavioral tests (Children's Communication Checklist [CCC-2], Social Responsiveness Scale [SRS], Aberrant Behavior Checklist [ABC], Clinical Global Impressions-Severity [CGI-S] and -Improvement [CGI-I], Autism Diagnostic Observation Schedule [ADOS], and Peabody Picture Vocabulary Test [PPVT]). Secondary endpoints included experimental biomarkers such as CD154, toll-like receptor-4, memory B cells, FOXP3, and lymphocyte stimulation. Significant improvements from baseline to study endpoint were observed in several subscales of the CCC-2, SRS, CGI-I, CGI-S, and ADOS, including Associated Maladaptive Behaviors (P ≤ .043), Reciprocal Social Interaction (P = .015), Communication (P < .001), and Stereotyped Behaviors and Repetitive Interests (P ≤ .013). Statistically significant reductions were also seen in numerous secondary outcomes of immunological biomarkers indicative of neuroinflammation. IVIG was well tolerated; no subjects withdrew due to an adverse event, and clinical data showed no evidence of thromboembolic events. Autism Res 2018, 11: 421-433. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay summary: Since research has demonstrated a link between autism spectrum disorder (ASD) and immune dysfunction, this study investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. Fourteen patients received IVIG treatment and were assessed using standardized cognitive and behavioral tests. Following treatment with IVIG, significant improvement was observed across several subscales of the clinical tests and significant reductions were seen in the markers of neuroinflammation. These data suggest that inflammatory etiologies may play a role in select cases of autism, and IVIG treatment may exert a positive impact on behaviors and markers of inflammation in ASD.

Keywords: autism spectrum disorder; epigenetic; innate immunity; intravenous immunoglobulin; neuroinflammation.

Publication types

  • Clinical Trial, Phase IV
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / blood
  • Autism Spectrum Disorder / complications*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Biomarkers / blood
  • CD40 Ligand / blood
  • CD40 Ligand / drug effects
  • Child
  • Child, Preschool
  • Female
  • Forkhead Transcription Factors / blood
  • Forkhead Transcription Factors / drug effects
  • Humans
  • Immune System Diseases / blood
  • Immune System Diseases / complications*
  • Immune System Diseases / drug therapy*
  • Immunoglobulins, Intravenous / blood
  • Immunoglobulins, Intravenous / therapeutic use*
  • Inflammation / blood
  • Inflammation / drug therapy*
  • Inflammation / prevention & control
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Neuroprotective Agents / blood
  • Neuroprotective Agents / therapeutic use*
  • Pilot Projects
  • Toll-Like Receptor 4 / blood
  • Toll-Like Receptor 4 / drug effects


  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunoglobulins, Intravenous
  • Neuroprotective Agents
  • Toll-Like Receptor 4
  • CD40 Ligand