Table 1.

Immune Dysfunction and Behaviors in ASD

Studies in chronological order	# in Study	Age	Assessment Method	Immune Measure	Behavior Measure
(Scifo et al., 1996)	12	7–15	BSE and CARS	Ratio of CD4 to CD8 positive T-cells	Administration of naltrexone led to reduction of “autistic” symptomology and increased ratio of CD4 to CD8 cells
(Gupta et al., 1996)	25	3–12	No formal testing	immunoglobuli n levels	IVIG resulted in improvements in eye contact, calmer behavior, improvement in speech and echolalia
(Plioplys, 1998)	10	4–17	No formal testing	IVIG	IVIG treatment resulted in transient improvements in attention span and hyperactivity; improvement declined after 5 months
(Sandler et al., 2000)	11	3–6	CARS	GI issues	Improvements in communication and asocial behaviors after vancomycin treatment, but were lost after conclusion of treatment
(Shenoy et al., 2000)	1	2	No formal testing	Autoimmune liymphoprolfer ative syndrome(ALPS)	Treatment with prednisone resulted in marked improvement in social and communication skills
(Curran et al., 2007)	60	2–18	ABC	Fever	Fewer aberrant behaviors were recorded for subjects with fever (>100.4°F) compared with controls. Improvements were transient.
(Ashwood et al., 2008)	143	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Plasma levels of active TGFβ1	Lower TGFβ1 levels were associated with lower adaptive behaviors and worse behavioral symptoms
(Iwata et al., 2008a)	37	20–25	ADI-R	Plasma levels of P-selectin	Lower levels of P-selectin associated with poor social development
(Heuer et al., 2008)	271	2–5	ADI-R, ADOS, ABC	IgG levels in plasma	Decreased IgG associated with increased aberrant behaviors
(Grigorenko et al., 2008)	1059	n.s.	ADI-R and ADOS	Genotyping of the MIF gene, and plasma levels of MIF(n=20)	Plasma MIF levels were positively correlated with worse scores on ADOS for social impairment and imaginative skills
(Onore et al., 2009)	60	2–5	ADOS, ADI-R, MSEL, VABS and ABC	Induced cytokine response to PHA	Negative correlation between PHA induced IL-23 production and sociability scores of the ADOS
(Enstrom et al., 2010)	30	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Monocyte TLR ligand stimulation	More impaired social behaviors and non-verbal communication are associated with increased production of IL-1β and IL-6 after TLR4 stimulation
(Ashwood et al., 2010)	139	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Induced cytokine response to PHA and LPS	Pro-inflammatory or TH1 cytokines were associated with greater impairments in core features of ASD as well as aberrant behaviors; GM-CSF and TH2 cytokines were associated with better cognitive and adaptive function
(Goines et al., 2010)	466	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Antibodies directed against a 45 or 62 kDa cerebellum protein	Children with antibodies directed against a 45 kDa cerebellum protein had increased, lethargy and stereotypy; children with antibodies against a 62 kDa cerebellum protein showed increased aberrant behaviors on the VABS composite standard score
(Kajizuka et al., 2010a)	62	6–19	ADI-R	Serum levels of PDGF	Increased serum levels of PDGF-BB homodimers positively associated with increased restricted, repetitive and stereotyped patterns of behavior and interests
(Ashwood et al., 2011c)	175	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Plasma Chemokines CCL2, CCL5 and eotaxin	Plasma chemokine levels associated with higher aberrant behavior scores and more impaired developmental and adaptive function
(Ashwood et al., 2011b)	223	2–5	ADI-R, ADOS, SCQ, VABS, MSEL, ABC	Plasma levels of cytokines IL-1β, IL-6, IL-8 and IL-12p40	Elevated cytokine levels in plasma were associated with more impaired communication and aberrant behaviors

BSE = Behavior Summarized Evaluation; ABC = Aberrant Behavior Checklist; CARS = Childhood autism rating scale; ADI-R = Autism Diagnostic Interview, Revised; ADOS = Autism Diagnostic Observation Schedule; SCQ = Social Communication Questionnaire; VABS = Vineland Adaptive Behavior Scale; GI = gastrointestinal; MIF = macrophage migration inhibitory factor; PDGF = platelet derived growth factor